Download PDF

Clinical Trial Results:
An Open-Label, Phase I/II, Dose-Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Patients with Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin’s Lymphoma and in Combination with Endocrine Therapy in Patients with Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer

Summary
EudraCT number	2012-002042-21
Trial protocol	FR
Global end of trial date	25 Jun 2021

Results information
Results version number	v1(current)
This version publication date	10 Jul 2022
First version publication date	10 Jul 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

PMT4979g

ISRCTN number

US NCT number

NCT01296555

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

25 Jun 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

25 Jun 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective of this study was to assess the clinical efficacy of the combination of GDC-0032 and fulvestrant, as measured by the clinical benefit rate and objective response rate, in all participants and participants with PIK3CA-mutated breast cancer.

Protection of trial subjects

All participants (or their parents or guardians) were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Mar 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 28

Country: Number of subjects enrolled

Spain: 136

Country: Number of subjects enrolled

France: 18

Country: Number of subjects enrolled

United States: 492

Worldwide total number of subjects

674

EEA total number of subjects

154

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

432

From 65 to 84 years

232

85 years and over

Subject disposition

Top of page

Recruitment details

Participants took part in this study at 30 centers in Canada, France, Spain, and United States from 16 March 2011 to 25 June 2021.

Screening details

Phase I: locally advanced or metastatic solid malignancy or NHL; post-menopausal locally advanced or metastatic hormone receptor-positive breast cancer (BC) +/- HER2-negative; NHL and DLBCL regardless of PIK3CA mutation; PIK3CA-mutant tumors. Phase II: post-menopausal locally advanced or metastatic HER2-negative, hormone receptor-positive BC.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase I, Stage 1: GDC-0032 3 milligrams (mg) once daily (QD)

Arm description

Participants received GDC-0032 3 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received taselisib 3 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles.

Phase I, Stage 1: GDC-0032 5 mg QD

Arm description

Participants received GDC-0032 5 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 5 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles.

Phase I, Stage 1: GDC-0032 8 mg QD

Arm description

Participants received GDC-0032 8 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 8 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles.

Phase I, Stage 1: GDC-0032 12 mg QD

Arm description

Participants received GDC-0032 12 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 12 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles.

Phase I, Stage 1: GDC-0032 16 mg QD

Arm description

Participants received GDC-0032 16 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 16 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles.

Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD

Arm description

Participants with PIK3CA-mutant breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 9 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles.

Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD

Arm description

Participants with PIK3CA-mutant solid tumors other than breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 9 mg capsules, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg

Arm description

Participants with any type of solid tumors were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD on Days 2 to 29 along with midazolam 5 mg syrup, orally, once on Days 1 and 16 of Cycle 1 (Cycle 1 duration=29 days) followed by GDC-0032 9 mg capsules, orally, QD in subsequent 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Syrup

Routes of administration

Oral use

Dosage and administration details

Participants received midazolam 5 mg syrup, orally, once on Days 1 and 16 of Cycle 1 (Cycle 1 duration=29 days) and QD in subsequent 28-day cycles.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 9 mg capsules, orally, QD on Days 2 to 29 and QD in subsequent 28-day cycles.

Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD

Arm description

Participants with HER2-positive breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, soft, Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 9 mg capsules, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort E –GDC-0032 6 mg QD + Letro 2.5 mg QD

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 6 mg and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 6 mg capsules, orally, QD in 28-day cycles.

Investigational medicinal product name

Letrozole

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received letrozole 2.5 mg capsules, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort E -GDC-0032 9 mg QD + Letro 2.5 mg QD

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 9 mg and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Letrozole

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received letrozole 2.5 mg capsules, orally, QD in 28-day cycles.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 9 mg capsules, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort F - GDC-0032 6 mg QD + Fulv 500 mg

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 6 mg capsules, orally, QD in 28-day cycles along with fulvestrant 500 mg, intramuscularly (IM) on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Participants received fulvestrant 500 mg, intramuscularly (IM) on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 6 mg capsules, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort F - GDC-0032 9 mg QD + Fulv 500 mg

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 9 mg capsules, orally, QD in 28-day cycles.

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Participants received fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD

Arm description

Participants with solid tumors with increased PIK3CA copy number were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 9 mg capsules, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD

Arm description

Participants with PIK3CA-mutant solid tumors that are non-breast and non-colorectal cancer were enrolled in this cohort to receive GDC-0032 6 mg tablets, orally, QD on Days 1 to 21 of each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 6 mg tablets, orally, QD on Days 1 to 21 of each 28-day cycle.

Phase I, Stage 2: Cohort J - GDC-0032 4 mg + Fulv 500 mg

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1 to 21 of each 28-day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally, QD on Days 1 to 21 of each 28-day cycle.

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Participants received fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Phase I, Stage 2: Cohort K - GDC-0032 4 mg + Fulv 500 mg

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Participants received fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally, QD on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle.

Phase I, Stage 2: Cohort L - GDC-0032 4 mg + Fulv 500 mg

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1-7 and 15-21 of each 28-day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally, QD on Days 1-7 and 15-21 of each 28-day cycle.

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Participants received fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Phase I, Stage 2: Cohort M - GDC-0032 2 mg QD + Fulv 500 mg

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 2 mg tablets, orally, QD in each 28-day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle until disease progression.

Arm type

Experimental

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Participants received fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 2 mg tablets, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort N -GDC-0032 2 mg QD + Letro 2.5 mg QD

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 2 mg tablets and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Letrozole

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received letrozole 2.5 mg capsules, orally, QD in 28-day cycles.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 2 mg tablets, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort P -GDC-0032 4 mg QD + Letro 2.5 mg QD

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Letrozole

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received letrozole 2.5 mg capsules, orally, QD in 28-day cycles.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort Q - GDC-0032 4 mg + Letro 2.5 mg QD

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1 to 21 along with letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally, QD on Days 1 to 21 in 28-day cycles.

Investigational medicinal product name

Letrozole

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received letrozole 2.5 mg capsules, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort R - GDC-0032 4 mg + Letro 2.5 mg QD

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally on Days 1-5, 8-12, 15-19, and 22-26 along with letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Letrozole

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received letrozole 2.5 mg capsules, orally, QD in 28-day cycles.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle.

Phase I, Stage 2: Cohort S - GDC-0032 4 mg + Letro 2.5 mg QD

Arm description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally on Days 1-7 and 15-21 along with letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Letrozole

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received letrozole 2.5 mg capsules, orally, QD in 28-day cycles.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally on Days 1-7 and 15-21 of each 28-day cycle.

Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD

Arm description

Participants with non-Hodgkin’s lymphoma that had progressed or had failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally QD in 28-day cycles.

Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD

Arm description

Participants with DLBCL who had progressed or had failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD

Arm description

Participants with PIK3CA-mutant solid tumors that have progressed or failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 4 mg tablets, orally, QD in 28-day cycles.

Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD

Arm description

Participants with PIK3CA-mutant solid tumors that had progressed or failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC-0032 6 mg tablets, orally QD in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 6 mg tablets, orally QD in 28-day cycles.

Phase II: GDC-0032 6 mg QD + Fulv 500 mg

Arm description

Postmenopausal participants with locally advanced or metastatic HER2-negative, hormone receptor-positive breast cancer who had not previously received fulvestrant were enrolled in this cohort to receive GDC-0032 6 mg tablets, orally, QD in 28-day cycles along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Participants received fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Investigational medicinal product name

Taselisib

Investigational medicinal product code

Other name

GDC-0032

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received GDC-0032 6 mg tablets, orally, QD in 28-day cycles.

Number of subjects in period 1	Phase I, Stage 1: GDC-0032 3 milligrams (mg) once daily (QD)	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD	Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg	Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort E –GDC-0032 6 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort E -GDC-0032 9 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort F - GDC-0032 6 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort F - GDC-0032 9 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD	Phase I, Stage 2: Cohort J - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort K - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort L - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort M - GDC-0032 2 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort N -GDC-0032 2 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort P -GDC-0032 4 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort Q - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort R - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort S - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD	Phase II: GDC-0032 6 mg QD + Fulv 500 mg
Started	6	3	4	10	11	20	20	13	10	20	8	21	6	21	35	20	20	19	20	27	28	20	20	20	10	10	70	122	60
Completed	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0
Not completed	6	3	4	10	11	20	20	13	10	20	8	20	6	21	35	20	20	18	20	27	28	20	20	20	10	10	70	121	60
Adverse event, serious fatal	-	-	-	2	1	-	2	-	-	1	-	1	-	2	27	15	11	11	17	12	13	12	12	13	7	7	35	92	44
Physician decision	-	-	-	-	1	-	-	-	-	-	-	-	-	1	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-
Consent withdrawn by subject	-	-	-	-	1	-	1	-	-	-	1	1	-	-	3	-	2	1	-	1	1	1	3	-	-	-	8	4	2
Use of Another Anti-Cancer Therapy	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	2	-	-	-	-	-	-	-	-	-
Adverse event, non-fatal	-	-	1	1	2	4	1	4	3	1	-	4	1	4	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-
Study Terminated By Sponsor	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-
Reason Not Specified	-	-	-	-	-	-	-	-	-	-	-	-	-	1	2	3	7	4	3	7	11	5	5	7	2	2	19	11	9
Progressive Disease	6	3	3	7	6	16	16	8	7	18	7	14	5	12	1	1	-	-	-	1	-	-	-	-	1	-	5	1	-
Non-Compliance With Study Drug	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Lost to follow-up	-	-	-	-	-	-	-	-	-	-	-	-	-	-	2	1	-	2	-	2	3	2	-	-	-	-	3	13	5
Protocol deviation	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

Phase I, Stage 1: GDC-0032 3 milligrams (mg) once daily (QD)

Reporting group description

Participants received GDC-0032 3 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 5 mg QD

Reporting group description

Participants received GDC-0032 5 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 8 mg QD

Reporting group description

Participants received GDC-0032 8 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 12 mg QD

Reporting group description

Participants received GDC-0032 12 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 16 mg QD

Reporting group description

Participants received GDC-0032 16 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD

Reporting group description

Participants with PIK3CA-mutant solid tumors other than breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD

Reporting group description

Participants with HER2-positive breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort E –GDC-0032 6 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort E -GDC-0032 9 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort F - GDC-0032 6 mg QD + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort F - GDC-0032 9 mg QD + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD

Reporting group description

Participants with solid tumors with increased PIK3CA copy number were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in each 28-day cycle until disease progression.

Reporting group title

Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort J - GDC-0032 4 mg + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort K - GDC-0032 4 mg + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort L - GDC-0032 4 mg + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort M - GDC-0032 2 mg QD + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort N -GDC-0032 2 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort P -GDC-0032 4 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort Q - GDC-0032 4 mg + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort R - GDC-0032 4 mg + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort S - GDC-0032 4 mg + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD

Reporting group description

Reporting group title

Phase II: GDC-0032 6 mg QD + Fulv 500 mg

Reporting group description

Reporting group values	Phase I, Stage 1: GDC-0032 3 milligrams (mg) once daily (QD)	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD	Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg	Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort E –GDC-0032 6 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort E -GDC-0032 9 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort F - GDC-0032 6 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort F - GDC-0032 9 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD	Phase I, Stage 2: Cohort J - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort K - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort L - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort M - GDC-0032 2 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort N -GDC-0032 2 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort P -GDC-0032 4 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort Q - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort R - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort S - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD	Phase II: GDC-0032 6 mg QD + Fulv 500 mg	Total
Number of subjects	6	3	4	10	11	20	20	13	10	20	8	21	6	21	35	20	20	19	20	27	28	20	20	20	10	10	70	122	60	674
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	51.0 ± 9.2	49.0 ± 12.5	66.3 ± 12.8	60.7 ± 15.4	57.9 ± 11.9	56.8 ± 11.6	62.6 ± 11.9	61.7 ± 9.6	50.4 ± 9.5	63.5 ± 9.7	59.1 ± 7.6	59.8 ± 11.9	55.0 ± 9.7	64.4 ± 10.0	64.3 ± 11.8	61.8 ± 7.7	62.8 ± 9.1	54.3 ± 12.7	55.7 ± 11.9	63.1 ± 9.1	59.7 ± 12.5	57.2 ± 13.9	58.3 ± 8.9	59.5 ± 10.6	66.1 ± 7.8	53.9 ± 19.3	60.6 ± 13.4	58.9 ± 11.9	60.3 ± 12.2	-
Sex: Female, Male
Units: participants
Female	4	2	2	9	6	19	12	6	10	20	8	21	6	16	22	20	20	19	20	27	28	20	20	19	6	2	37	83	60	544
Male	2	1	2	1	5	1	8	7	0	0	0	0	0	5	13	0	0	0	0	0	0	0	0	1	4	8	33	39	0	130
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2
Asian	0	0	0	1	1	0	0	0	0	0	0	1	0	0	1	0	0	1	2	1	0	1	0	0	0	0	4	3	3	19
Black or African American	0	0	0	1	0	1	0	0	0	0	0	0	0	0	1	1	0	1	0	0	1	1	2	0	0	0	2	4	3	18
Native Hawaiian or other Pacific Islande	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2
White	6	3	4	8	8	18	20	12	10	20	8	19	6	20	30	19	20	17	17	26	27	18	18	20	10	9	57	109	53	612
Other	0	0	0	0	1	1	0	1	0	0	0	1	0	0	3	0	0	0	1	0	0	0	0	0	0	0	7	5	0	20
Multiple	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	1	0	0	1	0	1	0	0	0	0	0	1	0	2	1	2	0	1	0	0	2	1	0	0	0	2	5	6	0	26
Not Hispanic or Latino	5	3	4	7	10	19	20	12	9	18	8	20	6	18	31	17	20	17	18	24	25	18	19	20	10	8	61	108	56	611
Unknown	0	0	0	2	0	0	0	1	0	1	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	2	2	1	11
Not Reported	0	0	0	0	1	0	0	0	1	1	0	0	0	0	3	1	0	1	1	3	1	1	1	0	0	0	2	6	3	26

End points

Top of page

Reporting group title

Phase I, Stage 1: GDC-0032 3 milligrams (mg) once daily (QD)

Reporting group description

Participants received GDC-0032 3 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 5 mg QD

Reporting group description

Participants received GDC-0032 5 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 8 mg QD

Reporting group description

Participants received GDC-0032 8 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 12 mg QD

Reporting group description

Participants received GDC-0032 12 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 16 mg QD

Reporting group description

Participants received GDC-0032 16 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD

Reporting group description

Participants with PIK3CA-mutant solid tumors other than breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD

Reporting group description

Participants with HER2-positive breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort E –GDC-0032 6 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort E -GDC-0032 9 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort F - GDC-0032 6 mg QD + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort F - GDC-0032 9 mg QD + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD

Reporting group description

Participants with solid tumors with increased PIK3CA copy number were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in each 28-day cycle until disease progression.

Reporting group title

Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort J - GDC-0032 4 mg + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort K - GDC-0032 4 mg + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort L - GDC-0032 4 mg + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort M - GDC-0032 2 mg QD + Fulv 500 mg

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort N -GDC-0032 2 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort P -GDC-0032 4 mg QD + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort Q - GDC-0032 4 mg + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort R - GDC-0032 4 mg + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort S - GDC-0032 4 mg + Letro 2.5 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD

Reporting group description

Reporting group title

Phase II: GDC-0032 6 mg QD + Fulv 500 mg

Reporting group description

Subject analysis set title

Phase I, Stage 1: GDC-0032 3 mg QD

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received GDC-0032 3 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Subject analysis set title

All Cohorts (Except T and T2)

Subject analysis set type

Safety analysis

Subject analysis set description

Participants from Cohorts from Phase I Stage 1, Cohorts A, B, C, D, E, F, G, H, J, K, L, M, N, P, Q, R, S, X and Phase 2 were included in this analysis.

Subject analysis set title

Cohorts T and T2

Subject analysis set type

Safety analysis

Subject analysis set description

Participants from Cohorts T and T2 of Phase I, Stage 2 were included in this analysis.

Subject analysis set title

GDC-0032 Monotherapy

Subject analysis set type

Safety analysis

Subject analysis set description

Participants who received GDC-0032 as monotherapy in Stage 1, Stage 2 (Cohorts A, B, C, D, G, H, T, T2, X) of Phase 1, and in Phase 2 were included in this analysis population.

Subject analysis set title

GDC-0032 + Letrozole

Subject analysis set type

Safety analysis

Subject analysis set description

Participants who received GDC-0032 in combination with letrozole in Stage 2 (Cohorts E, N, P, Q, R, S) were included in this analysis population.

Subject analysis set title

GDC-0032 + Fulvestrant

Subject analysis set type

Safety analysis

Subject analysis set description

Participants who received GDC-0032 in combination with fulvestrant in Stage 2 (Cohorts F, J, K, L, M) of Phase 1, and in Phase 2 were included in this analysis population.

Subject analysis set title

Cohort E

Subject analysis set type

Safety analysis

Subject analysis set description

Participants from Cohort E of Phase I, Stage 2 were included in this analysis.

Primary: Phase I Stage 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0)

Top of page

End point title

Phase I Stage 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) ^[1] ^[2]

End point description

A DLT is defined as any one of the following toxicities occurring within the DLT Assessment Window (Days 1-35 of Cycle 1 in Stage 1) assessed by the investigator: Grade ≥ 3 non-hematologic, non-hepatic organ system, non-metabolic (hyperglycemia and hyperlipidemia) toxicity, excluding alopecia of any grade, Grade 3 diarrhea, Grade 3 nausea or vomiting; Grade ≥ 4 thrombocytopenia; Grade ≥ 4 neutropenia lasting > 5 days or accompanied by fever; Fasting Grade ≥ 4 hyperglycemia or ≥ 3 hyperglycemia for ≥ 1 week; Grade ≥ 4 fasting hypercholesterolemia or triglyceridemia for ≥ 2 weeks; Grade ≥ 3 serum bilirubin or hepatic transaminase (ALT or AST); For participants abnormal at baseline: hepatic transaminase ≥ 7.5 × the upper limit of normal (ULN) or total bilirubin ≥ 5 × the ULN or 10 × the ULN or alkaline phosphatase ≥ 10 times the ULN. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Primary

End point timeframe

Baseline up to 35 days of Cycle 1

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD	Phase I, Stage 1: GDC-0032 3 mg QD
Number of subjects analysed	3	4	10	11	6
Units: percentage of participants
number (not applicable)	0.0	0.0	10.0	18.1	0.0

No statistical analyses for this end point

Primary: Phase I Stage 2 Cohorts E and F: Percentage of Participants with DLTs as Assessed by NCI CTCAE v4.0

Top of page

End point title

Phase I Stage 2 Cohorts E and F: Percentage of Participants with DLTs as Assessed by NCI CTCAE v4.0 ^[3] ^[4]

End point description

A DLT is defined as any one of the following toxicities occurring within the DLT Assessment Window (Days 1-28 of Cycle 1 in Stage 1) assessed by the investigator: Grade ≥ 3 non-hematologic, non-hepatic organ system, non-metabolic (hyperglycemia and hyperlipidemia) toxicity, excluding alopecia of any grade, Grade 3 diarrhea, Grade 3 nausea or vomiting; Grade ≥ 4 thrombocytopenia; Grade ≥ 4 neutropenia lasting > 5 days or accompanied by fever; Fasting Grade ≥ 4 hyperglycemia or ≥ 3 hyperglycemia for ≥ 1 week; Grade ≥ 4 fasting hypercholesterolemia or triglyceridemia for ≥ 2 weeks; Grade ≥ 3 serum bilirubin or hepatic transaminase (ALT or AST); For participants abnormal at baseline: hepatic transaminase ≥ 7.5 × ULN or total bilirubin ≥ 5 × the ULN or 10 × the ULN or alkaline phosphatase ≥ 10 times the ULN. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Primary

End point timeframe

Baseline up to 28 days of Cycle 1

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort E –GDC-0032 6 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort E -GDC-0032 9 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort F - GDC-0032 6 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort F - GDC-0032 9 mg QD + Fulv 500 mg
Number of subjects analysed	20	8	21	6
Units: percentage of participants
number (not applicable)	0.0	0.0	0.0	0.0

No statistical analyses for this end point

Primary: Phase I: AUC From Zero to tau (AUCtau) of GDC-0032

Top of page

End point title

Phase I: AUC From Zero to tau (AUCtau) of GDC-0032 ^[5] ^[6]

End point description

The concentrations are in micromole (µM), and the molecular weight of GDC-0032 is 460.53 g/mol. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant. 'n' signifies number of participants analysed for this outcome measure at the specified timepoint.

End point type

Primary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hours [hr]), 0.5, 1, 2, 3, 4, 8, 24, 48 and 72 hr; Day 15: Pre-dose (0-2 hr), 0.5, 1, 2, 3, 4, 8 and 24 hr

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 1: GDC-0032 3 milligrams (mg) once daily (QD)	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD
Number of subjects analysed	6	3	4	10	11
Units: micromolar per hour (µM*h)
arithmetic mean (standard deviation)
Day 1 (n=6, 3, 4, 10, 11)	0.441 ± 0.142	0.547 ± 0.233	1.34 ± 0.411	1.8 ± 0.631	2.26 ± 0.806
Day 15 (n=6, 3, 3, 10, 9)	1.79 ± 0.962	1.49 ± 0.786	3.21 ± 1.636	5.1 ± 2.035	8.1 ± 4.790

No statistical analyses for this end point

Primary: Phase I: Maximum Observed Plasma Concentration (Cmax) of GDC-0032

Top of page

End point title

Phase I: Maximum Observed Plasma Concentration (Cmax) of GDC-0032 ^[7] ^[8]

End point description

The concentrations are in µM, and the molecular weight of GDC-0032 is 460.53 g/mol. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant. 'n' signifies number of participants analysed for this outcome measure at the specified timepoint.

End point type

Primary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hours [hr]), 0.5, 1, 2, 3, 4, 8, 24, 48 and 72 hr; Day 15: Pre-dose (0-2 hr), 0.5, 1, 2, 3, 4, 8 and 24 hr

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD	Phase I, Stage 1: GDC-0032 3 mg QD
Number of subjects analysed	3	4	10	11	6
Units: micromolar (µM)
arithmetic mean (standard deviation)
Day 1 (n=3, 4, 10, 11, 6)	0.0304 ± 0.0122	0.0764 ± 0.0328	0.127 ± 0.0529	0.134 ± 0.0535	0.0256 ± 0.0094
Day 15 (n=3, 3, 10, 9, 6)	0.091 ± 0.048	0.188 ± 0.119	0.302 ± 0.100	0.441 ± 0.251	0.111 ± 0.072

No statistical analyses for this end point

Primary: Phase I: Time to Reach Cmax (tmax) of GDC-0032

Top of page

End point title

Phase I: Time to Reach Cmax (tmax) of GDC-0032 ^[9] ^[10]

End point description

The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Primary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hours [hr]), 0.5, 1, 2, 3, 4, 8, 24, 48 and 72 hr; Day 15: Pre-dose (0-2 hr), 0.5, 1, 2, 3, 4, 8 and 24 hr

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD	Phase I, Stage 1: GDC-0032 3 mg QD
Number of subjects analysed	3	4	10	11	6
Units: hours (hr)
median (full range (min-max))	8 (3 to 8)	4 (2 to 4)	3 (1 to 8)	4 (2 to 24)	4 (3 to 8)

No statistical analyses for this end point

Primary: Phase I: Terminal Half-life (t1/2) of GDC-0032

Top of page

End point title

Phase I: Terminal Half-life (t1/2) of GDC-0032 ^[11] ^[12]

End point description

The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Primary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hours [hr]), 0.5, 1, 2, 3, 4, 8, 24, 48 and 72 hr; Day 15: Pre-dose (0-2 hr), 0.5, 1, 2, 3, 4, 8 and 24 hr

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD	Phase I, Stage 1: GDC-0032 3 mg QD
Number of subjects analysed	3	4	10	11	6
Units: hr
arithmetic mean (standard deviation)	40 ± 21.0	38.2 ± 9.1	36.7 ± 8.3	39.7 ± 8.0	43.8 ± 11.6

No statistical analyses for this end point

Primary: Across All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response (BOR) as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Top of page

End point title

Across All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response (BOR) as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) ^[13]

End point description

BOR was defined as having best objective response as complete response (CR) or partial response (PR), as assessed by RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Primary

End point timeframe

Baseline up to disease progression or death, whichever occurred first (up to a maximum of 67 months)

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint

End point values	All Cohorts (Except T and T2)
Number of subjects analysed	674
Units: percentage of participants
number (confidence interval 95%)	11.4 (9.1 to 14.1)

No statistical analyses for this end point

Primary: Across All Cohorts (Except Cohorts T and T2): Duration of Objective Response (DOR) as Assessed Using RECIST v1.1

Top of page

End point title

Across All Cohorts (Except Cohorts T and T2): Duration of Objective Response (DOR) as Assessed Using RECIST v1.1 ^[14]

End point description

DOR was defined as time from first occurrence of a documented objective response(OR) to progressive disease(PD) or death from any cause(whichever occurred first) as determined by investigator according to RECIST v1.1. OR=CR+PR. CR: disappearance of all target lesions. PR: At least a 30% decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in absence of CR. PD: at least 20% increase in sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to relative increase of 20%, sum of diameters must also demonstrate an absolute increase of >/= 5 mm. Safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant. ‘99999’ signifies data was not estimable due to insufficient number of responders and insufficient amount of time passed to measure DOR. ‘Number of subjects analyzed’ signifies number of responders.

End point type

Primary

End point timeframe

Baseline up to disease progression or death, whichever occurred first (up to a maximum of 67 months)

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint

End point values	All Cohorts (Except T and T2)
Number of subjects analysed	77
Units: months
median (confidence interval 95%)	99999 (-99999 to 99999)

No statistical analyses for this end point

Primary: Across All Cohorts (Except Cohorts T and T2): Progression-Free Survival (PFS) as Assessed Using RECIST v1.1

Top of page

End point title

Across All Cohorts (Except Cohorts T and T2): Progression-Free Survival (PFS) as Assessed Using RECIST v1.1 ^[15]

End point description

PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause (whichever occurred first), as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm). The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Primary

End point timeframe

Baseline up to disease progression or death, whichever occurred first (up to a maximum of 67 months)

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint

End point values	All Cohorts (Except T and T2)
Number of subjects analysed	674
Units: months
median (confidence interval 95%)	3.7 (3.6 to 4.2)

No statistical analyses for this end point

Primary: Percentage of Participants With BOR in Cohort T and T2

Top of page

End point title

Percentage of Participants With BOR in Cohort T and T2 ^[16]

End point description

BOR in Cohort T was assessed using the 2007 Revised International Working Group (IWG) Response Criteria in Malignant Lymphoma while in Cohort T2, BOR was assessed using the Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Primary

End point timeframe

Baseline up to disease progression or death, whichever occurs first (up to a maximum of 46 months)

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint

End point values	Cohorts T and T2
Number of subjects analysed	20
Units: percentage of participants
number (confidence interval 95%)	20.0 (5.7 to 43.7)

No statistical analyses for this end point

Primary: DOR in Cohort T and T2

Top of page

End point title

DOR in Cohort T and T2 ^[17]

End point description

DOR in Cohort T was assessed using the 2007 Revised IWG Response Criteria in Malignant Lymphoma while in Cohort T2, it was assessed using the Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant. '99999' signifies data was not estimable due to insufficient number of responders and insufficient amount of time passed to measure DOR. 'Number of subjects analyzed' signifies the number of responders.

End point type

Primary

End point timeframe

Baseline up to disease progression or death, whichever occurs first (up to a maximum of 46 months)

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint

End point values	Cohorts T and T2
Number of subjects analysed	4
Units: months
median (confidence interval 95%)	99999 (-99999 to 99999)

No statistical analyses for this end point

Primary: PFS in Cohort T and T2

Top of page

End point title

PFS in Cohort T and T2 ^[18]

End point description

PFS in Cohort T was assessed using the 2007 Revised IWG Response Criteria in Malignant Lymphoma while in Cohort T2, it was assessed using the Modified Version of 2014 Lugano Response Criteria in Malignant Lymphoma. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant. '99999' signifies upper limit of 95% confidence interval (CI) was not estimable due to low number of participants with events.

End point type

Primary

End point timeframe

Baseline up to disease progression or death, whichever occurs first (up to a maximum of 46 months)

Notes
[18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been specified for this endpoint

End point values	Cohorts T and T2
Number of subjects analysed	20
Units: months
median (confidence interval 95%)	4.2 (1.8 to 99999)

No statistical analyses for this end point

Secondary: Phase I Stage 1: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) by NCI CTCAE v4.0 grade

Top of page

End point title

Phase I Stage 1: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) by NCI CTCAE v4.0 grade ^[19]

End point description

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. An SAE is any AE that is fatal, life-threatening, requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product(s) or considered a significant medical event by the investigator. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Secondary

End point timeframe

From first dose up to 30 days after the last dose of study drug or study discontinuation/termination (Up to a maximum of 16 months)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 1: GDC-0032 5 mg QD	Phase I, Stage 1: GDC-0032 8 mg QD	Phase I, Stage 1: GDC-0032 12 mg QD	Phase I, Stage 1: GDC-0032 16 mg QD	Phase I, Stage 1: GDC-0032 3 mg QD
Number of subjects analysed	3	4	10	11	6
Units: percentage of participants
number (not applicable)
AEs	100.0	100.0	100.0	100.0	100.0
SAEs	0	50.0	40.0	81.8	16.7

No statistical analyses for this end point

Secondary: Phase I Stage 2: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade

Top of page

End point title

Phase I Stage 2: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade ^[20]

End point description

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an IMP or other protocol-imposed intervention, regardless of attribution. An SAE is any AE that is fatal, life-threatening, requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity, a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product(s) or considered a significant medical event by the investigator. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Secondary

End point timeframe

From first dose up to 30 days after the last dose of study drug or study discontinuation/termination (Up to a maximum of 67 months)

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg	Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort E –GDC-0032 6 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort E -GDC-0032 9 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort F - GDC-0032 6 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort F - GDC-0032 9 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD	Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD	Phase I, Stage 2: Cohort J - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort K - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort L - GDC-0032 4 mg + Fulv 500 mg	Phase I, Stage 2: Cohort M - GDC-0032 2 mg QD + Fulv 500 mg	Phase I, Stage 2: Cohort N -GDC-0032 2 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort P -GDC-0032 4 mg QD + Letro 2.5 mg QD	Phase I, Stage 2: Cohort Q - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort R - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort S - GDC-0032 4 mg + Letro 2.5 mg QD	Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD	Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD
Number of subjects analysed	20	20	13	10	20	8	21	6	21	35	20	20	19	20	27	28	20	20	20	10	10	70	122
Units: percentage of participants
number (not applicable)
AEs	100.0	100.0	92.3	100.0	100.0	87.5	100.0	100.0	100.0	100.0	95.0	95.0	100.0	100.0	100.0	96.4	100.0	100.0	95.0	100.0	100.0	100.0	99.2
SAEs	45.0	35.0	53.8	40.0	55.0	25.0	23.8	50.0	42.9	54.3	20.0	35.0	15.8	30.0	22.2	35.7	10.0	25.0	10.0	70.0	40.0	57.1	51.6

No statistical analyses for this end point

Secondary: Phase II: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade

Top of page

End point title

Phase II: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade ^[21]

End point description

End point type

Secondary

End point timeframe

From first dose up to 30 days after the last dose of study drug or study discontinuation/termination (Up to a maximum of 54 months)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase II: GDC-0032 6 mg QD + Fulv 500 mg
Number of subjects analysed	60
Units: percentage of participants
number (not applicable)
AEs	100.0
SAEs	31.7

No statistical analyses for this end point

Secondary: Percentage of Participants with Clinical Relevant Shifts from Baseline in Laboratory Parameters

Top of page

End point title

Percentage of Participants with Clinical Relevant Shifts from Baseline in Laboratory Parameters

End point description

Laboratory parameters such as fasting glucose, absolute neutrophil count, hemoglobin, platelet count, lymphocytes, serum creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT), leukocytes, fasting triglycerides and fasting cholesterol were assessed. A clinical relevant shift from baseline was defined as a shift from Grade 0, 1, or 2 at baseline to Grade 3 or 4 post baseline. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Secondary

End point timeframe

Baseline to a maximum of 67 months

End point values	GDC-0032 Monotherapy	GDC-0032 + Letrozole	GDC-0032 + Fulvestrant
Number of subjects analysed	365	143	166
Units: percentage of participants
number (not applicable)
High Fasting Glucose	9.3	4.9	3.0
Low Fasting Glucose	0	0	0
Low Absolute Neutrophil Count	4.8	0	0.7
High Hemoglobin	0	0	0
Low Hemoglobin	5.2	0.7	1.2
Low Platelet Count	1.5	0.7	0.6
High Lymphocytes	0	0.9	0
Low Lymphocytes	13.9	7.3	2.9
High Serum Creatinine	0.9	0	2.5
High AST	2.6	6.3	7.0
High ALT	2.0	4.2	5.2
High Leukocytes	0	0	0
Low Leukocytes	2.1	1.4	0
High Fasting Triglycerides	0.4	0.9	0.8
High Fasting Cholesterol	0	0	0

No statistical analyses for this end point

Secondary: Cmax of GDC-0032 Under Fed Conditions

Top of page

End point title

Cmax of GDC-0032 Under Fed Conditions ^[22]

End point description

For dosing under fed conditions, participant fasted overnight for >/= 10 hours before the standard high-fat meal provided at the study site. Participants started the standard high fat meal 30 minutes prior to administration of GDC-0032. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Secondary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hr), 1, 2, 3, 4, 8, and 24 hr; Day 8: Pre-dose (0-2 hr), 1, 2, 3, 4, 8 and 24 hr

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD
Number of subjects analysed	20
Units: µM
arithmetic mean (standard deviation)	0.082 ± 0.038

No statistical analyses for this end point

Secondary: AUC of GDC-0032 Under Fed Conditions

Top of page

End point title

AUC of GDC-0032 Under Fed Conditions ^[23]

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hr), 1, 2, 3, 4, 8, and 24 hr; Day 8: Pre-dose (0-2 hr), 1, 2, 3, 4, 8 and 24 hr

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD
Number of subjects analysed	20
Units: µM*hr
arithmetic mean (standard deviation)	1.404 ± 0.656

No statistical analyses for this end point

Secondary: Cmax of GDC-0032 Under Fasted Conditions

Top of page

End point title

Cmax of GDC-0032 Under Fasted Conditions ^[24]

End point description

Participants fasted overnight for at least 10 hours before dosing and 4 hours postdose. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Secondary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hr), 1, 2, 3, 4, 8, and 24 hr; Day 8: Pre-dose (0-2 hr), 1, 2, 3, 4, 8 and 24 hr

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD
Number of subjects analysed	20
Units: µM
arithmetic mean (standard deviation)	0.085 ± 0.046

No statistical analyses for this end point

Secondary: AUC of GDC-0032 Under Fasted Conditions

Top of page

End point title

AUC of GDC-0032 Under Fasted Conditions ^[25]

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hr), 1, 2, 3, 4, 8, and 24 hr; Day 8: Pre-dose (0-2 hr), 1, 2, 3, 4, 8 and 24 hr

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD
Number of subjects analysed	20
Units: µM*hr
arithmetic mean (standard deviation)	1.247 ± 0.911

No statistical analyses for this end point

Secondary: Geometric Mean Ratio of Cmax for Midazolam plus GDC-0032 Relative to Cmax for Midazolam Alone

Top of page

End point title

Geometric Mean Ratio of Cmax for Midazolam plus GDC-0032 Relative to Cmax for Midazolam Alone ^[26]

End point description

The geometric mean ratio (90% CI) for midazolam+ GDC-0032 relative to midazolam alone was reported. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Secondary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hr; Day 16: Pre-dose (0-2 hr), 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hr

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg
Number of subjects analysed	13
Units: geometric mean ratio
number (confidence interval 90%)	0.98 (0.70 to 1.37)

No statistical analyses for this end point

Secondary: Geometric Mean Ratio of AUC for Midazolam plus GDC-0032 Relative to AUC for Midazolam Alone

Top of page

End point title

Geometric Mean Ratio of AUC for Midazolam plus GDC-0032 Relative to AUC for Midazolam Alone ^[27]

End point description

The geometric mean ratios (90% CIs) for midazolam + GDC-0032 relative to midazolam alone were reported. The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

End point type

Secondary

End point timeframe

Cycle 1, Day 1: Pre-dose (0-2 hr), 0.5, 1, 1.5, 2, 4, 8, 24 hr; Day 16: Pre-dose (0-2 hr), 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hr

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data for this endpoint was collected for the participants in Phase 1 Stage 1 only

End point values	Phase I, Stage 2: Cohort C -GDC-0032 9 mg QD + Mida 5 mg
Number of subjects analysed	13
Units: geometric mean ratio
number (confidence interval 90%)	1.04 (0.68 to 1.60)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose up to 30 days after the last dose of study drug or study discontinuation/termination (Up to approximately 68 months)

Adverse event reporting additional description

The safety-evaluable population was defined as all participants who received at least one dose of GDC-0032, letrozole, or fulvestrant.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Phase I,Stage 1: GDC-0032 3 milligrams(mg) once daily(QD)

Reporting group description

Participants received GDC-0032 3 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 5 mg QD

Reporting group description

Participants received GDC-0032 5 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 16 mg QD

Reporting group description

Participants received GDC 0032 16 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28- day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 8 mg QD

Reporting group description

Participants received GDC-0032 8 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 1: GDC-0032 12 mg QD

Reporting group description

Participants received GDC 0032 12 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD

Reporting group description

Participants with PIK3CA mutant solid tumors other than breast cancer were enrolled in this cohort to receive GDC 0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD

Reporting group description

Participants with PIK3CA mutant breast cancer were enrolled in this cohort to receive GDC 0032 9 mg capsules, orally, once on Day 1 and then QD on Days 8 to 35 of Cycle 1 (Cycle 1 duration=35 days) and in subsequent 28- day cycles until disease progression.

Reporting group title

Phase I,Stage 2:Cohort C- GDC-0032 9 mg QD+Midazolam 5 mg

Reporting group description

Participants with any type of solid tumors were enrolled in this cohort to receive GDC 0032 9 mg capsules, orally, QD on Days 2 to 29 along with midazolam 5 mg syrup, orally, once on Days 1 and 16 of Cycle 1 (Cycle 1 duration=29 days) followed by GDC-0032 9 mg capsules, orally, QD in subsequent 28- day cycles until disease progression.

Reporting group title

Phase I,Stage 2: Cohort E-GDC-0032 6mg QD+Letrozole 2.5mg QD

Reporting group description

Postmenopausal participants with hormone receptor-positive breast cancer were enrolled in this cohort to receive GDC 0032 6 mg and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD

Reporting group description

Participants with HER2- positive breast cancer were enrolled in this cohort to receive GDC 0032 9 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I,Stage 2: Cohort E-GDC-0032 9mg QD+Letrozole 2.5mg QD

Reporting group description

Postmenop ausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 9 mg and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I,Stage 2:Cohort F-GDC-0032 6mg QD+Fulvestrant 500mg

Reporting group description

Postmenop ausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 6 mg capsules, orally, QD in 28-day cycles along with fulvestrant 500 mg, intramuscul arly (IM) on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28- day cycle until disease progression.

Reporting group title

Phase I, Stage 2: Cohort J-GDC-0032 4mg+Fulvestrant 500mg

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1 to 21 of each 28- day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28- day cycle until disease progression .

Reporting group title

Phase I,Stage 2:Cohort F-GDC-0032 9mg QD+Fulvestrant 500mg

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 9 mg capsules, orally, QD in 28-day cycles along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28- day cycle until disease progression.

Reporting group title

Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD

Reporting group description

Participa nts with solid tumors with increase d PIK3CA copy number were enrolled in this cohort to receive GDC 0032 9 mg capsules , orally, QD in each 28- day cycle until disease progress ion

Reporting group title

Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD

Reporting group description

Participants with PIK3CA mutant solid tumors that are non breast and non colorect al cancer were enrolled in this cohort to receive GDC 0032 6 mg tablets, orally, QD on Days 1 to 21 of each 28- day cycle until disease progress ion.

Reporting group title

Phase I,Stage 2: Cohort L-GDC-0032 4mg + Fulvestrant 500mg

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1- 7 and 15-21 of each 28- day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28- day cycle until disease progression.

Reporting group title

Phase I,Stage 2: Cohort M-GDC-0032 2mg QD+Fulvestrant 500mg

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 2 mg tablets, orally, QD in each 28- day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28- day cycle until disease progression.

Reporting group title

Phase I,Stage 2:Cohort N-GDC-0032 2mg QD+Letrozole 2.5mg QD

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 2 mg tablets and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I,Stage 2:Cohort K-GDC-0032 4mg+Fulvestrant 500mg

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1- 5, 8-12, 15- 19, and 22- 26 of each 28-day cycle along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28- day cycle until disease progression.

Reporting group title

Phase I,Stage 2:Cohort R-GDC-0032 4mg+Letrozole 2.5mg QD

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally on Days 1-5, 8-12, 15- 19, and 22- 26 along with letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I,Stage 2:Cohort P-GDC-0032 4mg QD+Letrozole 2.5mg QD

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets and letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I,Stage 2:Cohort Q-GDC-0032 4mg+Letrozole 2.5mg QD

Reporting group description

Postmenopausal participants with hormone receptor positive breast cancer were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD on Days 1 to 21 along with letrozole 2.5 mg capsules, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I,Stage 2:Cohort S-GDC-0032 4mg+Letrozole 2.5mg QD

Reporting group description

Reporting group title

Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD

Reporting group description

Participants with non Hodgkin’s lymphoma that had progressed or had failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC 0032 4 mg tablets, orally QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD

Reporting group description

Participants with DLBCL who had progressed or had failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC 0032 4 mg tablets, orally, QD in 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD

Reporting group description

Participants with PIK3CA mutant solid tumors that have progressed or failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC-0032 4 mg tablets, orally, QD in 28- day cycles until disease progression.

Reporting group title

Phase II: GDC-0032 6 mg QD + Fulvestrant 500 mg

Reporting group description

Postmenopausal participants with locally advanced or metastatic HER2-negative, hormone receptor-positive breast cancer who had not previously received fulvestrant were enrolled in this cohort to receive GDC 0032 6 mg tablets, orally, QD in 28-day cycles along with fulvestrant 500 mg, IM on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycles until disease progression.

Reporting group title

Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD

Reporting group description

Participants with PIK3CA mutant solid tumors that had progressed or failed to respond to at least one prior regimen were enrolled in this cohort to receive GDC-0032 6 mg tablets, orally QD in 28- day cycles until disease progression.

Phase I,Stage 1: GDC-0032 3 milligrams(mg) once daily(QD)

Phase I, Stage 1: GDC-0032 5 mg QD

Phase I, Stage 1: GDC-0032 16 mg QD

Phase I, Stage 1: GDC-0032 8 mg QD

Phase I, Stage 1: GDC-0032 12 mg QD

Phase I, Stage 2: Cohort B - GDC-0032 9 mg QD

Phase I, Stage 2: Cohort A - GDC-0032 9 mg QD

Phase I,Stage 2:Cohort C- GDC-0032 9 mg QD+Midazolam 5 mg

Phase I,Stage 2: Cohort E-GDC-0032 6mg QD+Letrozole 2.5mg QD

Phase I, Stage 2: Cohort D - GDC-0032 9 mg QD

Phase I,Stage 2: Cohort E-GDC-0032 9mg QD+Letrozole 2.5mg QD

Phase I,Stage 2:Cohort F-GDC-0032 6mg QD+Fulvestrant 500mg

Phase I, Stage 2: Cohort J-GDC-0032 4mg+Fulvestrant 500mg

Phase I,Stage 2:Cohort F-GDC-0032 9mg QD+Fulvestrant 500mg

Phase I, Stage 2: Cohort G - GDC-0032 9 mg QD

Phase I, Stage 2: Cohort H - GDC-0032 6 mg QD

Phase I,Stage 2: Cohort L-GDC-0032 4mg + Fulvestrant 500mg

Phase I,Stage 2: Cohort M-GDC-0032 2mg QD+Fulvestrant 500mg

Phase I,Stage 2:Cohort N-GDC-0032 2mg QD+Letrozole 2.5mg QD

Phase I,Stage 2:Cohort K-GDC-0032 4mg+Fulvestrant 500mg

Phase I,Stage 2:Cohort R-GDC-0032 4mg+Letrozole 2.5mg QD

Phase I,Stage 2:Cohort P-GDC-0032 4mg QD+Letrozole 2.5mg QD

Phase I,Stage 2:Cohort Q-GDC-0032 4mg+Letrozole 2.5mg QD

Phase I,Stage 2:Cohort S-GDC-0032 4mg+Letrozole 2.5mg QD

Phase I, Stage 2: Cohort T - GDC-0032 4 mg QD

Phase I, Stage 2: Cohort T2 - GDC-0032 4 mg QD

Phase I, Stage 2: Cohort X - GDC-0032 4 mg QD

Phase II: GDC-0032 6 mg QD + Fulvestrant 500 mg

Phase I, Stage 2: Cohort X - GDC-0032 6 mg QD

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 6 (16.67%)

0 / 3 (0.00%)

9 / 11 (81.82%)

2 / 4 (50.00%)

4 / 10 (40.00%)

7 / 20 (35.00%)

9 / 20 (45.00%)

7 / 13 (53.85%)

11 / 20 (55.00%)

4 / 10 (40.00%)

2 / 8 (25.00%)

5 / 21 (23.81%)

4 / 20 (20.00%)

3 / 6 (50.00%)

9 / 21 (42.86%)

19 / 35 (54.29%)

3 / 19 (15.79%)

6 / 20 (30.00%)

6 / 27 (22.22%)

7 / 20 (35.00%)

5 / 20 (25.00%)

10 / 28 (35.71%)

2 / 20 (10.00%)

7 / 10 (70.00%)

4 / 10 (40.00%)

40 / 70 (57.14%)

19 / 60 (31.67%)

63 / 122 (51.64%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

MALIGNANT PLEURAL EFFUSION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

1 / 13 (7.69%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

HYPOTENSION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 21 (4.76%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

2 / 122 (1.64%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

ARTERIAL RUPTURE

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

DEEP VEIN THROMBOSIS

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HYPERTENSION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

1 / 27 (3.70%)

0 / 20 (0.00%)

1 / 28 (3.57%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

1 / 60 (1.67%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LYMPHOEDEMA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SHOCK HAEMORRHAGIC

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

VENOUS THROMBOSIS

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

DEATH

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 21 (4.76%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

ASTHENIA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 21 (4.76%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FATIGUE

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 11 (9.09%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

1 / 28 (3.57%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

MUCOSAL INFLAMMATION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

1 / 20 (5.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

1 / 28 (3.57%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PAIN

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PYREXIA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

1 / 20 (5.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

1 / 27 (3.70%)

0 / 20 (0.00%)

2 / 28 (7.14%)

1 / 20 (5.00%)

0 / 20 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

2 / 70 (2.86%)

0 / 60 (0.00%)

2 / 122 (1.64%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 3

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

SOFT TISSUE INFLAMMATION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

SUDDEN DEATH

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Immune system disorders

HYPERSENSITIVITY

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

FEMALE GENITAL TRACT FISTULA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

OVARIAN CYST RUPTURED

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

PROSTATITIS

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

PNEUMONIA ASPIRATION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

1 / 20 (5.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

PULMONARY EMBOLISM

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

1 / 60 (1.67%)

3 / 122 (2.46%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 3

deaths causally related to treatment / all

0 / 0

ACUTE RESPIRATORY DISTRESS SYNDROME

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ACUTE RESPIRATORY FAILURE

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

2 / 70 (2.86%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

ANOXIA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ASTHMA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

ATELECTASIS

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

1 / 20 (5.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COUGH

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DYSPNOEA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

2 / 35 (5.71%)

1 / 19 (5.26%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

3 / 70 (4.29%)

0 / 60 (0.00%)

5 / 122 (4.10%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 2

0 / 1

0 / 0

0 / 3

0 / 0

0 / 6

deaths causally related to treatment / all

0 / 0

HAEMOPTYSIS

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

HYPOXIA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

2 / 70 (2.86%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

LARYNGEAL HAEMORRHAGE

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LUNG INFILTRATION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

1 / 10 (10.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

1 / 27 (3.70%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PLEURAL EFFUSION

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

2 / 20 (10.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 21 (4.76%)

1 / 35 (2.86%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

1 / 60 (1.67%)

2 / 122 (1.64%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

PNEUMONITIS

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 11 (9.09%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

1 / 13 (7.69%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

2 / 21 (9.52%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

2 / 122 (1.64%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

PNEUMOTHORAX

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

1 / 10 (10.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

2 / 35 (5.71%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

PULMONARY OEDEMA

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

PULMONARY TOXICITY

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RESPIRATORY FAILURE

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Psychiatric disorders

MENTAL STATUS CHANGES

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

1 / 70 (1.43%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Investigations

AMYLASE INCREASED

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

1 / 20 (5.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

BLOOD CREATININE INCREASED

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

1 / 122 (0.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

LIPASE INCREASED

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

0 / 20 (0.00%)

0 / 13 (0.00%)

1 / 20 (5.00%)

0 / 10 (0.00%)

0 / 8 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 21 (0.00%)

0 / 35 (0.00%)

0 / 19 (0.00%)

0 / 20 (0.00%)

0 / 27 (0.00%)

0 / 20 (0.00%)

0 / 28 (0.00%)

0 / 20 (0.00%)

0 / 10 (0.00%)

0 / 70 (0.00%)

0 / 60 (0.00%)

0 / 122 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TRANSAMINASES INCREASED

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 11 (0.00%)

0 / 4 (0.00%)

0 / 10 (0.00%)

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase I Stage 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0)

Primary: Phase I Stage 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0)

Primary: Phase I Stage 2 Cohorts E and F: Percentage of Participants with DLTs as Assessed by NCI CTCAE v4.0

Primary: Phase I Stage 2 Cohorts E and F: Percentage of Participants with DLTs as Assessed by NCI CTCAE v4.0

Primary: Phase I: AUC From Zero to tau (AUCtau) of GDC-0032

Primary: Phase I: AUC From Zero to tau (AUCtau) of GDC-0032

Primary: Phase I: Maximum Observed Plasma Concentration (Cmax) of GDC-0032

Primary: Phase I: Maximum Observed Plasma Concentration (Cmax) of GDC-0032

Primary: Phase I: Time to Reach Cmax (tmax) of GDC-0032

Primary: Phase I: Time to Reach Cmax (tmax) of GDC-0032

Primary: Phase I: Terminal Half-life (t1/2) of GDC-0032

Primary: Phase I: Terminal Half-life (t1/2) of GDC-0032

Primary: Across All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response (BOR) as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Primary: Across All Cohorts (Except Cohorts T and T2): Percentage of Participants With Best Overall Response (BOR) as Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Primary: Across All Cohorts (Except Cohorts T and T2): Duration of Objective Response (DOR) as Assessed Using RECIST v1.1

Primary: Across All Cohorts (Except Cohorts T and T2): Duration of Objective Response (DOR) as Assessed Using RECIST v1.1

Primary: Across All Cohorts (Except Cohorts T and T2): Progression-Free Survival (PFS) as Assessed Using RECIST v1.1

Primary: Across All Cohorts (Except Cohorts T and T2): Progression-Free Survival (PFS) as Assessed Using RECIST v1.1

Primary: Percentage of Participants With BOR in Cohort T and T2

Primary: Percentage of Participants With BOR in Cohort T and T2

Primary: DOR in Cohort T and T2

Primary: DOR in Cohort T and T2

Primary: PFS in Cohort T and T2

Primary: PFS in Cohort T and T2

Secondary: Phase I Stage 1: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) by NCI CTCAE v4.0 grade

Secondary: Phase I Stage 1: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) by NCI CTCAE v4.0 grade

Secondary: Phase I Stage 2: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade

Secondary: Phase I Stage 2: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade

Secondary: Phase II: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade

Secondary: Phase II: Percentage of Participants with AEs and SAEs by NCI CTCAE v4.0 grade

Secondary: Percentage of Participants with Clinical Relevant Shifts from Baseline in Laboratory Parameters

Secondary: Percentage of Participants with Clinical Relevant Shifts from Baseline in Laboratory Parameters

Secondary: Cmax of GDC-0032 Under Fed Conditions

Secondary: Cmax of GDC-0032 Under Fed Conditions

Secondary: AUC of GDC-0032 Under Fed Conditions

Secondary: AUC of GDC-0032 Under Fed Conditions

Secondary: Cmax of GDC-0032 Under Fasted Conditions

Secondary: Cmax of GDC-0032 Under Fasted Conditions

Secondary: AUC of GDC-0032 Under Fasted Conditions

Secondary: AUC of GDC-0032 Under Fasted Conditions

Secondary: Geometric Mean Ratio of Cmax for Midazolam plus GDC-0032 Relative to Cmax for Midazolam Alone

Secondary: Geometric Mean Ratio of Cmax for Midazolam plus GDC-0032 Relative to Cmax for Midazolam Alone

Secondary: Geometric Mean Ratio of AUC for Midazolam plus GDC-0032 Relative to AUC for Midazolam Alone

Secondary: Geometric Mean Ratio of AUC for Midazolam plus GDC-0032 Relative to AUC for Midazolam Alone

Adverse events