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Clinical Trial Results:
A Phase Ib /II open-label, multi-center study of the combination of BYL719 plus AMG 479 (ganitumab) in adult patients with selected advanced solid tumors

Summary
EudraCT number	2012-001962-13
Trial protocol	ES BE
Global end of trial date	01 Jun 2017

Results information
Results version number	v1(current)
This version publication date	16 Jun 2018
First version publication date	16 Jun 2018
Other versions

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

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Trial information

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Sponsor protocol code

CBYL719X2105J

ISRCTN number

US NCT number

NCT01708161

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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

01 Jun 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Jun 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

Phase Ib To estimate the maximum tolerated dose(s) (MTD) and/or identify the recommended phase II dose(s) (RPIID) of BYL719 in combination with ganitumab in patients with PIK3CA mutated or amplified solid tumors. Phase II To estimate the antitumor activity of BYL719 in combination with ganitumab in the following Phase II populations:  Arm 1: Patients with PIK3CA mutated or amplified hormone receptor positive breast cancer  Arm 2: Patients with PIK3CA mutated or amplified ovarian cancer

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Nov 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 11

Country: Number of subjects enrolled

Spain: 8

Country: Number of subjects enrolled

United States: 28

Worldwide total number of subjects

EEA total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Patients with selected advanced solid tumors who had relapsed or progressed on standard therapy were treated in BYL719X2105J study with a combination of alpelisib and ganitumab. Phase I of the trial was by dose combination of the treatment. Phase II was by patients.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

BYL 200mg + AMG 12mg/kg

Arm description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Arm type

Experimental

Investigational medicinal product name

BYL719 and AMG 479

Investigational medicinal product code

Other name

Alpelisib and Ganitumab

Pharmaceutical forms

Coated tablet, Solution for injection/infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

BYL719 was administered orally once daily (28 day cycles) upon completion of AMG 479 intravenous infusion (every second week (Days 1 and 15 of every cycle).

BYL 300mg + AMG 12mg/kg

Arm description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Arm type

Experimental

Investigational medicinal product name

BYL719 and AMG 479

Investigational medicinal product code

Other name

Alpelisib and Ganitumab

Pharmaceutical forms

Coated tablet, Solution for injection/infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

BYL719 was administered orally once daily (28 day cycles) upon completion of AMG 479 intravenous infusion (every second week (Days 1 and 15 of every cycle).

BYL 350mg + AMG 12mg/kg

Arm description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Arm type

Experimental

Investigational medicinal product name

BYL719 and AMG 479

Investigational medicinal product code

Other name

Alpelisib and Ganitumab

Pharmaceutical forms

Coated tablet, Solution for injection/infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

BYL719 was administered orally once daily (28 day cycles) upon completion of AMG 479 intravenous infusion (every second week (Days 1 and 15 of every cycle).

HR+BC - Phase II

Arm description

Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breast carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg.

Arm type

Experimental

Investigational medicinal product name

BYL719 and AMG 479

Investigational medicinal product code

Other name

Alpelisib and Ganitumab

Pharmaceutical forms

Coated tablet, Solution for injection/infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

BYL719 was administered orally once daily (28 day cycles) upon completion of AMG 479 intravenous infusion (every second week (Days 1 and 15 of every cycle).

Ovarian - Phase II

Arm description

Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg

Arm type

Experimental

Investigational medicinal product name

BYL719 and AMG 479

Investigational medicinal product code

Other name

Alpelisib and Ganitumab

Pharmaceutical forms

Coated tablet, Solution for injection/infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

BYL719 was administered orally once daily (28 day cycles) upon completion of AMG 479 intravenous infusion (every second week (Days 1 and 15 of every cycle).

Non-HR+BC/Ovarian - Phase II

Arm description

Patients with other than Breast and Ovarian cancer treated in the phase II part

Arm type

Experimental

Investigational medicinal product name

BYL719 and AMG 479

Investigational medicinal product code

Other name

Alpelisib and Ganitumab

Pharmaceutical forms

Coated tablet, Solution for injection/infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

BYL719 was administered orally once daily (28 day cycles) upon completion of AMG 479 intravenous infusion (every second week (Days 1 and 15 of every cycle).

Number of subjects in period 1	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg	HR+BC - Phase II	Ovarian - Phase II	Non-HR+BC/Ovarian - Phase II
Started	4	10	10	16	6	1
Completed	0	0	0	0	0	0
Not completed	4	10	10	16	6	1
Adverse event, serious fatal	-	-	-	1	-	1
Consent withdrawn by subject	-	1	1	-	-	-
Disease progression	3	5	5	13	3	-
Adverse event, non-fatal	1	3	4	2	3	-
Administrative problems	-	1	-	-	-	-

Baseline characteristics

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Reporting group title

BYL 200mg + AMG 12mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Reporting group title

BYL 300mg + AMG 12mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Reporting group title

BYL 350mg + AMG 12mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Reporting group title

HR+BC - Phase II

Reporting group description

Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breast carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg.

Reporting group title

Ovarian - Phase II

Reporting group description

Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg

Reporting group title

Non-HR+BC/Ovarian - Phase II

Reporting group description

Patients with other than Breast and Ovarian cancer treated in the phase II part

Reporting group values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg	HR+BC - Phase II	Ovarian - Phase II	Non-HR+BC/Ovarian - Phase II	Total
Number of subjects	4	10	10	16	6	1	47
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	4	7	4	15	4	1	35
From 65-84 years	0	3	6	1	2	0	12
85 years and over	0	0	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	50.5 ( 3.11 )	57.5 ( 15.55 )	63.7 ( 7.83 )	51.3 ( 8.04 )	59.7 ( 6.53 )	56.0 ( 0 )	-
Sex: Female, Male
Units: Subjects
Female	4	7	7	15	6	1	40
Male	0	3	3	1	0	0	7

End points

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Reporting group title

BYL 200mg + AMG 12mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Reporting group title

BYL 300mg + AMG 12mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Reporting group title

BYL 350mg + AMG 12mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Reporting group title

HR+BC - Phase II

Reporting group description

Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breast carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg.

Reporting group title

Ovarian - Phase II

Reporting group description

Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg

Reporting group title

Non-HR+BC/Ovarian - Phase II

Reporting group description

Patients with other than Breast and Ovarian cancer treated in the phase II part

Subject analysis set title

All Patients - Phase

Subject analysis set type

Full analysis

Subject analysis set description

The total column “All patients” includes a patient with non-HR+BC and non-Ovarian cancer treated in the Phase II part.

Subject analysis set title

All Patients - Phase II

Subject analysis set type

Full analysis

Subject analysis set description

The total column “All patients” includes a patient with non-HR+BC and non-Ovarian cancer treated in the Phase II part.

Primary: Dose limiting toxicities (DLTs) - Phase Ib

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End point title

Dose limiting toxicities (DLTs) - Phase Ib ^[1] ^[2]

End point description

Phase lb only

End point type

Primary

End point timeframe

28 days

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: Descriptive analyses.
[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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	3	8	9
Units: Participants
Drug hypersensitivity\|	0	0	1
Hyperglycemia\|	0	0	1
Rash maculopapular\|	0	1	0
Urticaria\|	0	1	0

No statistical analyses for this end point

Primary: Percentage of Patients with overall response rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

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End point title

Percentage of Patients with overall response rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II ^[3] ^[4]

End point description

The antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Overall response rate is defined as the proportion of patients who have a best overall response of complete response or partial response assessed per RECIST 1.1.

End point type

Primary

End point timeframe

Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)

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: Descriptive analyses.
[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: Descriptive analyses.

End point values	HR+BC - Phase II	Ovarian - Phase II	All Patients - Phase
Number of subjects analysed	16	6	23
Units: Percentages of participants
number (confidence interval 95%)	12.5 (1.6 to 38.3)	16.7 (0.4 to 64.1)	13.0 (2.8 to 33.6)

No statistical analyses for this end point

Secondary: Number of Patients with best overall response (RECIST) based on investigator radiology assessment - Phase Ib

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End point title

Number of Patients with best overall response (RECIST) based on investigator radiology assessment - Phase Ib ^[5]

End point description

The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1

End point type

Secondary

End point timeframe

Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)

Notes
[5] - 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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: Participants
Complete response (CR)\|	0	0	0
Partial response (PR)\|	0	0	3
Stable disease (PD)\|	1	3	2
Progressive disease (PD)\|	3	3	3
Unknown\|	0	4	2

No statistical analyses for this end point

Secondary: Percentage of Patients with disease control rate (RECIST) based on investigator radiology assessment - Phase Ib

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End point title

Percentage of Patients with disease control rate (RECIST) based on investigator radiology assessment - Phase Ib ^[6]

End point description

The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1

End point type

Secondary

End point timeframe

Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)

Notes
[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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: Percentages
number (confidence interval 95%)	25.0 (0.6 to 80.6)	9.1 (6.7 to 65.2)	50.0 (18.7 to 81.3)

No statistical analyses for this end point

Secondary: Percentage of patients with disease control rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

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End point title

Percentage of patients with disease control rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II ^[7]

End point description

the antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter

End point type

Secondary

End point timeframe

Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)

Notes
[7] - 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: Descriptive analyses.

End point values	HR+BC - Phase II	Ovarian - Phase II	All Patients - Phase II
Number of subjects analysed	16	6	23
Units: Percentages of participants
number (confidence interval 95%)	43.8 (19.8 to 70.1)	50.0 (11.8 to 88.2)	47.8 (26.8 to 69.4)

No statistical analyses for this end point

Secondary: Cmax of BYL - Phase Ib

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End point title

Cmax of BYL - Phase Ib ^[8]

End point description

Serum concentration for BYL719 (alpelisib); cycle 1 = initial 28 days of treatment

End point type

Secondary

End point timeframe

Cycle 1 Day 1, Cycle 1 Day 15

Notes
[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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1\|	2070 ( 1040 )	2620 ( 1260 )	2640 ( 888 )
Cycle 1 day 15\|	3080 ( 1750 )	2880 ( 910 )	2600 ( 1040 )

No statistical analyses for this end point

Secondary: Area under curve (AUC) 0-24 hour of BYL - Phase Ib

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End point title

Area under curve (AUC) 0-24 hour of BYL - Phase Ib ^[9]

End point description

Area under curve for BYL719 (Alpelisib); cycle 1 = initial 28 days of treatment

End point type

Secondary

End point timeframe

Cycle 1 Day 1, Cycle 1 Day 15

Notes
[9] - 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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: hr*ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1\|	19900 ( 8700 )	23400 ( 10500 )	25200 ( 9200 )
Cycle 1 day 15\|	24000 ( 10700 )	29700 ( 9170 )	25200 ( 9160 )

No statistical analyses for this end point

Secondary: Tmax and T half of BYL - Phase Ib

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End point title

Tmax and T half of BYL - Phase Ib ^[10]

End point description

Tmax and half life of BYL719 (Alpelisib); cycle 1 = initial 28 days of treatment

End point type

Secondary

End point timeframe

Cycle 1 Day 1, Cycle 1 Day 15

Notes
[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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: hr
median (full range (min-max))
Tmax (Cycle 1 Day 1)\|	2.78 (1.88 to 3.55)	1.97 (0.63 to 3.00)	2.36 (1.50 to 3.10)
Tmax (Cycle 1 Day 15)\|	1.57 (0.83 to 1.83)	3.01 (2.07 to 4.00)	2.02 (2.00 to 3.08)
Thalf (Cycle 1 Day 1)\|	7.78 (6.24 to 10.80)	6.06 (5.26 to 13.70)	6.86 (5.32 to 9.23)
Thalf (Cycle 1 Day15)\|	6.89 (5.94 to 9.90)	6.80 (5.82 to 8.81)	6.83 (5.19 to 13.00)

No statistical analyses for this end point

Secondary: Cmax of AMG - Phase Ib

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End point title

Cmax of AMG - Phase Ib ^[11]

End point description

Serum concentration for AMG 479 (ganitumab); cycle 1 = initial 28 days of treatment

End point type

Secondary

End point timeframe

Cycle 1 Day 15

Notes
[11] - 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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: ng/mL
arithmetic mean (standard deviation)	192 ( 24 )	202 ( 43.3 )	232 ( 59.3 )

No statistical analyses for this end point

Secondary: Area under curve (AUC) 0-336 hour of AMG - Phase Ib

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End point title

Area under curve (AUC) 0-336 hour of AMG - Phase Ib ^[12]

End point description

Area under curve for AMG 479 (ganitumab); cycle 1 = initial 28 days of treatment

End point type

Secondary

End point timeframe

Cycle 1 Day 15

Notes
[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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: hr*ng/mL
arithmetic mean (standard deviation)	22900 ( 3930 )	22500 ( 7040 )	25200 ( 8000 )

No statistical analyses for this end point

Secondary: Tmax and T half of AMG - Phase Ib

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End point title

Tmax and T half of AMG - Phase Ib ^[13]

End point description

Tmax and half life of AMG 479 (ganitumab); cycle 1 = initial 28 days of treatment

End point type

Secondary

End point timeframe

Cycle 1 Day 15

Notes
[13] - 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: Descriptive analyses.

End point values	BYL 200mg + AMG 12mg/kg	BYL 300mg + AMG 12mg/kg	BYL 350mg + AMG 12mg/kg
Number of subjects analysed	4	10	10
Units: hr
median (full range (min-max))
Tmax\|	21.20 (1.02 to 22.70)	1.02 (1.00 to 23.10)	1.07 (1.00 to 1.77)
Thalf\|	132 (117 to 148)	117 (109 to 161)	180 (98 to 283)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events (SAE) field “number of deaths resulting from adverse events” all those deaths, resulting from SAE that are deemed to be causally related to treatment by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

BYL 200mg + AMG 12 mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors.

Reporting group title

BYL 300mg + AMG 12 mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors.

Reporting group title

BYL 350mg + AMG 12 mg/kg

Reporting group description

BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors

Reporting group title

HR + BC - Phase II

Reporting group description

Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breat carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg

Reporting group title

Ovarian - Phase II

Reporting group description

Patients with other than Breast and Ovarian cancer treated in the phase II

Serious adverse events	BYL 200mg + AMG 12 mg/kg	BYL 300mg + AMG 12 mg/kg	BYL 350mg + AMG 12 mg/kg	HR + BC - Phase II	Ovarian - Phase II
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 4 (25.00%)	5 / 10 (50.00%)	5 / 10 (50.00%)	9 / 16 (56.25%)	5 / 6 (83.33%)
number of deaths (all causes)	0	1	1	1	0
number of deaths resulting from adverse events	0	0	0	0	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Female genital tract fistula
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute interstitial pneumonitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fracture displacement
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct stenosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bile duct stone
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Myositis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	2 / 16 (12.50%)	3 / 6 (50.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	3 / 3	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperuricaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	BYL 200mg + AMG 12 mg/kg	BYL 300mg + AMG 12 mg/kg	BYL 350mg + AMG 12 mg/kg	HR + BC - Phase II	Ovarian - Phase II
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	10 / 10 (100.00%)	10 / 10 (100.00%)	16 / 16 (100.00%)	6 / 6 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Vascular disorders
Flushing
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Hypertension
subjects affected / exposed	2 / 4 (50.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	2	0	0	2	0
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0
Lymphoedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Peripheral venous disease
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	3 / 16 (18.75%)	3 / 6 (50.00%)
occurrences all number	0	3	2	4	3
Axillary pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Catheter site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Chills
subjects affected / exposed	1 / 4 (25.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)
occurrences all number	1	1	2	3	2
Face oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Fatigue
subjects affected / exposed	2 / 4 (50.00%)	6 / 10 (60.00%)	8 / 10 (80.00%)	7 / 16 (43.75%)	2 / 6 (33.33%)
occurrences all number	2	6	12	8	2
Feeling abnormal
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Feeling cold
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Gait disturbance
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Injection site rash
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Instillation site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Localised oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Malaise
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Mucosal inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	3 / 16 (18.75%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0
Non-cardiac chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)
occurrences all number	0	0	1	3	1
Oedema peripheral
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	2	1	1	0
Pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Pyrexia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	4 / 16 (25.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1	4	2
Thirst
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Hypersensitivity
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Seasonal allergy
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Pelvic pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0
Vulvovaginal dryness
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Choking
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Cough
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	6 / 16 (37.50%)	2 / 6 (33.33%)
occurrences all number	0	2	0	7	3
Dysphonia
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Dyspnoea
subjects affected / exposed	0 / 4 (0.00%)	4 / 10 (40.00%)	0 / 10 (0.00%)	4 / 16 (25.00%)	1 / 6 (16.67%)
occurrences all number	0	4	0	6	1
Dyspnoea exertional
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Epistaxis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Hypoxia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Laryngeal haemorrhage
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)
occurrences all number	0	2	0	3	1
Paranasal sinus discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Paranasal sinus hypersecretion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	0	3	0
Pneumothorax
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Productive cough
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Respiratory tract congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Rhinitis allergic
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Rhinorrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)
occurrences all number	0	0	0	3	1
Sinus congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Anxiety
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	0	1	1	1
Confusional state
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)
occurrences all number	0	0	1	2	1
Depression
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	1	0	1	1
Insomnia
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	4 / 10 (40.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	1	4	2	0
Libido decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Mental status changes
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)
occurrences all number	0	1	0	2	1
Amylase increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	4 / 16 (25.00%)	2 / 6 (33.33%)
occurrences all number	0	2	1	4	2
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Blood bilirubin increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	2 / 6 (33.33%)
occurrences all number	0	1	1	1	2
Blood calcium decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Blood cholesterol increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Blood creatine phosphokinase MB increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	2
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Blood creatinine increased
subjects affected / exposed	3 / 4 (75.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	0 / 16 (0.00%)	2 / 6 (33.33%)
occurrences all number	3	4	7	0	2
Blood magnesium decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	2
Blood phosphorus decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	1
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Lipase increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)
occurrences all number	0	3	0	3	1
Neutrophil count decreased
subjects affected / exposed	1 / 4 (25.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	2	0	0	0
Neutrophil count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Platelet count decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	1	0	0
Weight decreased
subjects affected / exposed	2 / 4 (50.00%)	5 / 10 (50.00%)	9 / 10 (90.00%)	6 / 16 (37.50%)	2 / 6 (33.33%)
occurrences all number	2	6	10	6	3
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Fall
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Hip fracture
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Infusion related reaction
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0
Wound
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Wound complication
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Palpitations
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	2 / 6 (33.33%)
occurrences all number	0	1	0	1	2
Nervous system disorders
Amnesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Aphonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Balance disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Disturbance in attention
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Dizziness
subjects affected / exposed	1 / 4 (25.00%)	3 / 10 (30.00%)	3 / 10 (30.00%)	2 / 16 (12.50%)	2 / 6 (33.33%)
occurrences all number	2	4	3	3	4
Dysarthria
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Dysgeusia
subjects affected / exposed	1 / 4 (25.00%)	4 / 10 (40.00%)	4 / 10 (40.00%)	3 / 16 (18.75%)	0 / 6 (0.00%)
occurrences all number	1	4	4	3	0
Headache
subjects affected / exposed	3 / 4 (75.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	5 / 16 (31.25%)	1 / 6 (16.67%)
occurrences all number	4	1	2	7	1
Hypoaesthesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Memory impairment
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Paraesthesia
subjects affected / exposed	1 / 4 (25.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0
Presyncope
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	2
Somnolence
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	1	0	0	2
Transient ischaemic attack
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	3 / 6 (50.00%)
occurrences all number	0	2	0	3	4
Leukocytosis
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0
Lymph node pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Neutropenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Thrombocytopenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Ear and labyrinth disorders
Ear congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	0
Ear pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Hearing impaired
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Tinnitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Eye disorders
Eye swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Eyelid ptosis
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	0	1
Periorbital oedema
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0
Photopsia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Vision blurred
subjects affected / exposed	1 / 4 (25.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	1	2	0	2	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	2
Abdominal distension
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	0
Abdominal pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	3 / 16 (18.75%)	2 / 6 (33.33%)
occurrences all number	0	1	2	4	2
Abdominal pain lower
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Abdominal pain upper
subjects affected / exposed	1 / 4 (25.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	1	1	2	1	1
Anal fissure
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Anal ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Anorectal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0
Aphthous stomatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Chapped lips
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Constipation
subjects affected / exposed	0 / 4 (0.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	4 / 16 (25.00%)	1 / 6 (16.67%)
occurrences all number	0	4	2	4	1
Diarrhoea
subjects affected / exposed	2 / 4 (50.00%)	5 / 10 (50.00%)	7 / 10 (70.00%)	10 / 16 (62.50%)	3 / 6 (50.00%)
occurrences all number	4	10	10	12	5
Dry mouth
subjects affected / exposed	1 / 4 (25.00%)	2 / 10 (20.00%)	3 / 10 (30.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)
occurrences all number	1	2	4	3	1
Dyspepsia
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	3 / 6 (50.00%)
occurrences all number	1	0	0	2	3
Dysphagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	1	2	0
Flatulence
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	1	0	2	0
Gingival bleeding
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Gingival erosion
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0
Gingival recession
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Haemorrhoids
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Mouth ulceration
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0
Nausea
subjects affected / exposed	0 / 4 (0.00%)	9 / 10 (90.00%)	5 / 10 (50.00%)	7 / 16 (43.75%)	3 / 6 (50.00%)
occurrences all number	0	12	7	10	3
Odynophagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Oesophagitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Oral pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Retching
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Sensitivity of teeth
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Small intestinal obstruction
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Stomatitis
subjects affected / exposed	3 / 4 (75.00%)	3 / 10 (30.00%)	5 / 10 (50.00%)	6 / 16 (37.50%)	3 / 6 (50.00%)
occurrences all number	3	3	9	6	5
Toothache
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Vomiting
subjects affected / exposed	0 / 4 (0.00%)	6 / 10 (60.00%)	4 / 10 (40.00%)	4 / 16 (25.00%)	3 / 6 (50.00%)
occurrences all number	0	13	6	12	9
Hepatobiliary disorders
Cholangitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Skin and subcutaneous tissue disorders
Acanthosis nigricans
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0
Alopecia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	0	1	1	1
Blister
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Dermatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0
Dry skin
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	1	1	0
Erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Hyperhidrosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Ingrowing nail
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Nail disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	0
Night sweats
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Onychoclasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Prurigo
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	4 / 16 (25.00%)	1 / 6 (16.67%)
occurrences all number	0	0	2	5	1
Rash
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	4 / 16 (25.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	4	0
Rash erythematous
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	3	0	0
Rash macular
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Rash maculo-papular
subjects affected / exposed	2 / 4 (50.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	5 / 16 (31.25%)	0 / 6 (0.00%)
occurrences all number	2	2	3	9	0
Rash pruritic
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Skin discolouration
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Urticaria
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Renal and urinary disorders
Bladder spasm
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Cystitis noninfective
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Dysuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	1	2	0
Hydronephrosis
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Micturition urgency
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Neurogenic bladder
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Pollakiuria
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	2	1	0
Polyuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Renal failure acute
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Renal impairment
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Urinary retention
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	0
Urinary tract pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 4 (25.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	4 / 16 (25.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	4	0
Back pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)
occurrences all number	0	0	0	3	1
Bone pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Flank pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0
Muscle spasms
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	4 / 16 (25.00%)	0 / 6 (0.00%)
occurrences all number	0	0	3	4	0
Muscular weakness
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	1	1	1	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	3 / 16 (18.75%)	0 / 6 (0.00%)
occurrences all number	0	0	1	3	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	2	2	0
Myalgia
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	3 / 16 (18.75%)	1 / 6 (16.67%)
occurrences all number	0	3	1	5	2
Myositis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Neck pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	5 / 16 (31.25%)	0 / 6 (0.00%)
occurrences all number	0	1	0	5	0
Spinal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Trismus
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Bronchitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Cellulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Conjunctivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Gastroenteritis viral
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0
Gingivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Herpes virus infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Localised infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	0	2	1	1
Nail infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Nasal herpes
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Nasopharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	0	1	1	1
Onychomycosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Oral candidiasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Paronychia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Periorbital cellulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Pharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1
Rash pustular
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Subcutaneous abscess
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	1 / 6 (16.67%)
occurrences all number	0	1	0	3	1
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	3 / 16 (18.75%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 4 (25.00%)	5 / 10 (50.00%)	6 / 10 (60.00%)	8 / 16 (50.00%)	6 / 6 (100.00%)
occurrences all number	1	5	7	9	6
Dehydration
subjects affected / exposed	1 / 4 (25.00%)	5 / 10 (50.00%)	4 / 10 (40.00%)	4 / 16 (25.00%)	1 / 6 (16.67%)
occurrences all number	1	20	5	8	2
Glucose tolerance impaired
subjects affected / exposed	1 / 4 (25.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	2	1	0	0
Gout
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Hypercalcaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0
Hyperglycaemia
subjects affected / exposed	1 / 4 (25.00%)	7 / 10 (70.00%)	9 / 10 (90.00%)	9 / 16 (56.25%)	4 / 6 (66.67%)
occurrences all number	1	11	20	18	12
Hyperkalaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0
Hypoglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0
Hypokalaemia
subjects affected / exposed	0 / 4 (0.00%)	3 / 10 (30.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 6 (0.00%)
occurrences all number	0	3	0	2	0
Hypomagnesaemia
subjects affected / exposed	0 / 4 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 16 (6.25%)	1 / 6 (16.67%)
occurrences all number	0	3	1	1	3
Hyponatraemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	2	0	1	0
Metabolic acidosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

21 Aug 2012

This amendment was to implement suggested changes from health authorities. The entry criteria were adjusted for patients with elevated blood glucose levels and for patients receiving prior platelet transfusions. Dose modification and DLT tables was amended for clarification. Storage conditions for both study treatments were included. Change was made to stagger the administration of concomitant medication affecting gastric pH relative to BYL719 administration.

11 Jan 2013

This amendment was to introduce local molecular pre-screening for patients whose status for PIK3CA mutation/amplification was not known. In addition, a central testing option at a Novartis designated laboratory was provided for molecular rescreening to patients with ovarian cancer enrolled in the Phase II part of the study. In addition, changes made to sampling and analyses of biomarkers were described as well.

30 May 2013

This amendment was to allow enrollment of patients who could not provide a fresh tumor biopsy at baseline into the study. Per the amendment, submission of an archival or a fresh tumor sample was acceptable. In addition, cells harvested from ascites or pleural effusions were accepted in lieu of fresh tumor samples.

26 Aug 2014

This amendment was released following the enrollment halt due to difficulty to enroll the patients and limited clinical activity. The protocol was amended to remove follow-up for progression and survival. Of note, there were no changes to the safety follow-up (including 30-day safety follow-up and follow-up for neutralizing antibodies).

17 Dec 2014

This amendment was released post recruitment halt in this study. This amendment was a consequence of an event of pneumonitis in another study with BYL719 requiring an urgent safety measure which was rolled out for all studies involving BYL719 to include guidelines for management of pneumonitis.

24 Jun 2016

This amendment was released after reaching the primary objective for Part Ib of the study and database lock for the primary data analysis. The purpose of the amendment was to reduce assessments for the three remaining patients while still ensuring appropriate safety monitoring. In particular, the visit evaluation schedule was modified, and no efficacy, pharmacokinetics, and biomarker assessments were collected. Only safety-related events were collected.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Due to the competitive landscape for anticancer therapies in ovarian and breast cancer and given the limited clinical activity observed with the study combination treatment, Novartis decided in 2014 to halt the recruitment in the trial.

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Clinical trials

Clinical Trial Results:
A Phase Ib /II open-label, multi-center study of the combination of BYL719 plus AMG 479 (ganitumab) in adult patients with selected advanced solid tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Dose limiting toxicities (DLTs) - Phase Ib

Primary: Dose limiting toxicities (DLTs) - Phase Ib

Primary: Percentage of Patients with overall response rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Primary: Percentage of Patients with overall response rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Secondary: Number of Patients with best overall response (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Number of Patients with best overall response (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Percentage of Patients with disease control rate (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Percentage of Patients with disease control rate (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Percentage of patients with disease control rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Secondary: Percentage of patients with disease control rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Secondary: Cmax of BYL - Phase Ib

Secondary: Cmax of BYL - Phase Ib

Secondary: Area under curve (AUC) 0-24 hour of BYL - Phase Ib

Secondary: Area under curve (AUC) 0-24 hour of BYL - Phase Ib

Secondary: Tmax and T half of BYL - Phase Ib

Secondary: Tmax and T half of BYL - Phase Ib

Secondary: Cmax of AMG - Phase Ib

Secondary: Cmax of AMG - Phase Ib

Secondary: Area under curve (AUC) 0-336 hour of AMG - Phase Ib

Secondary: Area under curve (AUC) 0-336 hour of AMG - Phase Ib

Secondary: Tmax and T half of AMG - Phase Ib

Secondary: Tmax and T half of AMG - Phase Ib

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase Ib /II open-label, multi-center study of the combination of BYL719 plus AMG 479 (ganitumab) in adult patients with selected advanced solid tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Dose limiting toxicities (DLTs) - Phase Ib

Primary: Dose limiting toxicities (DLTs) - Phase Ib

Primary: Percentage of Patients with overall response rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Primary: Percentage of Patients with overall response rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Secondary: Number of Patients with best overall response (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Number of Patients with best overall response (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Percentage of Patients with disease control rate (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Percentage of Patients with disease control rate (RECIST) based on investigator radiology assessment - Phase Ib

Secondary: Percentage of patients with disease control rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Secondary: Percentage of patients with disease control rate (RECIST) based on Investigator radiology assessment for HR positive breast and ovarian cancer - Phase II

Secondary: Cmax of BYL - Phase Ib

Secondary: Cmax of BYL - Phase Ib

Secondary: Area under curve (AUC) 0-24 hour of BYL - Phase Ib

Secondary: Area under curve (AUC) 0-24 hour of BYL - Phase Ib

Secondary: Tmax and T half of BYL - Phase Ib

Secondary: Tmax and T half of BYL - Phase Ib

Secondary: Cmax of AMG - Phase Ib

Secondary: Cmax of AMG - Phase Ib

Secondary: Area under curve (AUC) 0-336 hour of AMG - Phase Ib

Secondary: Area under curve (AUC) 0-336 hour of AMG - Phase Ib

Secondary: Tmax and T half of AMG - Phase Ib

Secondary: Tmax and T half of AMG - Phase Ib

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase Ib /II open-label, multi-center study of the combination of BYL719 plus AMG 479 (ganitumab) in adult patients with selected advanced solid tumors