Clinical Trial Results:
A Master Protocol Evaluating the Safety and Efficacy of Therapies for
Metastatic Castration-resistant Prostate Cancer (mCRPC)
Summary
|
|
EudraCT number |
2020-001305-23 |
Trial protocol |
DE NL SE DK IT |
Global end of trial date |
23 Oct 2023
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
07 Nov 2024
|
First version publication date |
07 Nov 2024
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
20190505
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04631601 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Amgen Inc.
|
||
Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, United States,
|
||
Public contact |
Amgen (EUROPE) GmbH, Amgen Inc., MedInfoInternational@amgen.com
|
||
Scientific contact |
Study Director, Amgen Inc., MedInfoInternational@amgen.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
23 Oct 2023
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
23 Oct 2023
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
The main objective was to evaluate the safety, tolerability and maximum tolerated dose or recommended phase 2 dose (RP2D) of acapatamab in combination with enzalutamide (Subprotocol A), acapatamab in combination with abiraterone (Subprotocol B), or acapatamab in combination with AMG 404 (Subprotocol C, Parts 1 and 2), evaluate preliminary antitumor activity of AMG monotherapy (Subprotocol C, Part 3) and to evaluate the safety and tolerability of acapatamab (Subprotocol D) in participants with mCRPC.
|
||
Protection of trial subjects |
This study was conducted in accordance with the protocol and with:
consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and applicable ICH laws and regulations.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Jan 2021
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 24
|
||
Country: Number of subjects enrolled |
Denmark: 5
|
||
Country: Number of subjects enrolled |
Spain: 17
|
||
Country: Number of subjects enrolled |
Sweden: 4
|
||
Country: Number of subjects enrolled |
United Kingdom: 4
|
||
Worldwide total number of subjects |
54
|
||
EEA total number of subjects |
26
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
16
|
||
From 65 to 84 years |
38
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||||||||||||||||||||
Recruitment details |
54 participants were enrolled at 11 centers in Denmark, Spain, Sweden, the United Kingdom, and the United States between 15 January 2021 and 23 October 2023. One additional participant was enrolled in Subprotocol D. To protect participant privacy, the results of this participant are not included in this summary. | |||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||||||||||||||||||||
Screening details |
A total of 54 participants were enrolled and 53 received study treatment. | |||||||||||||||||||||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||||||||||||||||||||
Period 1 title |
Main Study (overall period)
|
|||||||||||||||||||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
|||||||||||||||||||||||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||||||||||||||
Arm title
|
Subprotocol A: Acapatamab and Enzalutamide | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) extended intravenous (eIV) infusion, followed by the target dose (60-minute intravenous [IV] infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Enzalutamide
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet, Capsule
|
|||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Enzalutamide was taken as either oral capsules or oral tablets.
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Acapatamab
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||||||||
Other name |
AMG 160
|
|||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Powder for infusion
|
|||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Acapatamab was administered as a short-term or extended IV infusion.
|
|||||||||||||||||||||||||||||||||||||||||||||
Arm title
|
Subprotocol B: Acapatamab and Abiraterone | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Abiraterone
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Abiraterone was taken as oral tablets.
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Acapatamab
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||||||||
Other name |
AMG 160
|
|||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Powder for infusion
|
|||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Acapatamab was administered as a short-term or extended IV infusion.
|
|||||||||||||||||||||||||||||||||||||||||||||
Arm title
|
Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
AMG 404
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
AMG 404 was administered as a short-term IV infusion.
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Acapatamab
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||||||||
Other name |
AMG 160
|
|||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Powder for infusion
|
|||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
Acapatamab was administered as a short-term or extended IV infusion.
|
|||||||||||||||||||||||||||||||||||||||||||||
Arm title
|
Subprotocol C, Part 3: AMG 404 Monotherapy | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
AMG 404
|
|||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intravenous use
|
|||||||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
AMG 404 was administered as a short-term IV infusion.
|
|||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol A: Acapatamab and Enzalutamide
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) extended intravenous (eIV) infusion, followed by the target dose (60-minute intravenous [IV] infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol B: Acapatamab and Abiraterone
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol C, Part 3: AMG 404 Monotherapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Subprotocol A: Acapatamab and Enzalutamide
|
||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) extended intravenous (eIV) infusion, followed by the target dose (60-minute intravenous [IV] infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules. | ||
Reporting group title |
Subprotocol B: Acapatamab and Abiraterone
|
||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). | ||
Reporting group title |
Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
|
||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle. | ||
Reporting group title |
Subprotocol C, Part 3: AMG 404 Monotherapy
|
||
Reporting group description |
Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle. | ||
Subject analysis set title |
Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.
|
||
Subject analysis set title |
Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.
|
||
Subject analysis set title |
Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.
|
||
Subject analysis set title |
Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.
|
||
Subject analysis set title |
Subprotocol B (Cohort 1): Acapatamab and Abiraterone
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).
|
||
Subject analysis set title |
Subprotocol B (Cohort 2): Acapatamab and Abiraterone
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).
|
||
Subject analysis set title |
Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).
|
||
Subject analysis set title |
Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.
|
||
Subject analysis set title |
Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.
|
|
|||||||||||||
End point title |
Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) [1] [2] | ||||||||||||
End point description |
DLTs were defined as any adverse event (per Common Terminology Criteria for Adverse Events (CTCAE) v5: Grade 5=Death, Grade 4=Life-threatening, Grade 3=Moderate) occurring within 28 days of the first AMG 160 dose, possibly related to the treatment, including:
- Grade 5 toxicity
- Grade 4 thrombocytopenia
- Grade 3 thrombocytopenia with significant hemorrhage
- Grade 4 neutropenia > 5 days
- Febrile neutropenia
- Grade 3 anemia requiring transfusion
- Grade ≥3 non-hematologic toxicity (with exceptions per protocol)
- Aspartate transaminase/alanine transaminase >3x upper limit of normal (ULN) with serum total bilirubin >2x ULN without cholestasis or another clear cause
- Grade ≥3 non-hematological toxicity delaying treatment > 2 weeks or resulting in <75% dose administration
DLT Analysis Set: Included all participants who received at least one AMG 160 dose and had an evaluable DLT endpoint (had a DLT or completed all planned doses without a DLT within 28-day DLT window in Cycle 1).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 1 to Day 28
|
||||||||||||
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 were pre-planned 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [3] [4] | ||||||||||||||||||||
End point description |
A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment that started after the first dose of acapatamab, or AMG 404 (subprotocol C, parts 1 and 2), whichever was earlier.
A treatment-related TEAE was defined as a TEAE that had a reasonable possibility of being caused by acapatamab, or AMG 404 (subprotocol C, parts 1 and 2 only).
Clinically significant changes from baseline in vital signs and clinical laboratory tests were also recorded as TEAEs.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab, or AMG 404 (subprotocol C, parts 1 and 2 only).
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
From first dose of acapatamab/AMG 404 to the first of 30 days after last dose of acapatamab/AMG404, end of study date or the initiation of a new anticancer therapy (up to a maximum of 3 years).
|
||||||||||||||||||||
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 were pre-planned 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Subprotocol C, Part 3: Objective Response Rate (ORR) [5] [6] | ||||||||
End point description |
ORR was defined as the percentage of participants who experienced a complete response (CR) or partial response (PR), per response evaluation criteria in solid tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications. Responses were required to be confirmed at least 4 weeks later.
RECIST Evaluable Analysis Set: Included all participants that were enrolled and received at least 1 dose of AMG 404 and had measurable baseline disease per RECIST 1.1 and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
From Cycle 1 Day 1 until progression, start of new anticancer therapy, or up to 3 years after the first dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
|
||||||||
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 were pre-planned 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response [7] [8] | ||||||||
End point description |
CTC0 response was defined as CTC0 (reduction of CTCs > 0 to 0 at any post-baseline measurement). The baseline was defined as the last non-missing value on or prior to the pre-dose of AMG 404 assessments on Cycle 1 Day 1.
CTC0 Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of AMG 404 and had baseline CTC > 0.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
|
||||||||
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 were pre-planned 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response [9] [10] | ||||||||
End point description |
CTC conversion response was defined as ≥ 5 CTCs/7.5 mL blood at baseline that converted to ≤ 4 CTCs/7.5 mL blood at any post-baseline measurement. The baseline was defined as the last non-missing value on or prior to the pre-dose assessments of AMG 404 on Cycle 1 Day 1.
CTC Conversion Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of AMG 404 and had baseline CTC ≥ 5.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
|
||||||||
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 were pre-planned 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response [11] [12] | ||||||||||||||||
End point description |
A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later:
- PSA 30 response: ≥ 30% reduction from the baseline PSA.
- PSA 50 response: ≥ 50% reduction from the baseline PSA.
- PSA 70 response: ≥ 70% reduction from the baseline PSA.
- PSA 90 response: ≥ 90% reduction from the baseline PSA.
The baseline was defined as the last non-missing value on or prior to the pre-dose of AMG 404 assessments on Cycle 1 Day 1.
PSA Response Evaluable Set: Included all participants that were enrolled, received at least 1 dose of AMG 404, had measurable (i.e., > 0) baseline PSA and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Cycle 1 Day 1 to 5 months post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
|
||||||||||||||||
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 were pre-planned 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Subprotocols A. B and C (Parts 1 and 2): ORR [13] | ||||||||||||||||
End point description |
ORR was defined as the percentage of participants who experienced a CR or PR, per RECIST 1.1 with PCWG3 modifications. Responses were required to be confirmed at least 4 weeks later.
RECIST 1.1 Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of AMG 160 and had measurable baseline disease per RECIST 1.1 per protocol and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From Cycle 1 Day 1 until progression, start of new anticancer therapy, or up to 3 years after the first dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
|
||||||||||||||||
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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC Conversion Response [14] | ||||||||||||||||
End point description |
CTC conversion response was defined as ≥ 5 CTCs/7.5 mL blood at baseline that converted to ≤ 4 CTCs/7.5 mL blood at any post-baseline measurement. The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1.
CTC Conversion Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of acapatamab/AMG 404 and had baseline CTC ≥ 5.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Cycle 1 Day 1 to 14 days post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
|
||||||||||||||||
Notes [14] - 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC0 Response [15] | ||||||||||||||||
End point description |
CTC0 response was defined as CTC0 (reduction of CTCs > 0 to 0 at any post-baseline measurement). The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1.
CTC0 Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of acapatamab/AMG 404 and had baseline CTC > 0.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Cycle 1 Day 1 to 14 days post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
|
||||||||||||||||
Notes [15] - 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a PSA Response [16] | ||||||||||||||||||||||||||||||||
End point description |
A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later:
- PSA 30 response: ≥ 30% reduction from the baseline PSA.
- PSA 50 response: ≥ 50% reduction from the baseline PSA.
- PSA 70 response: ≥ 70% reduction from the baseline PSA.
- PSA 90 response: ≥ 90% reduction from the baseline PSA.
The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1.
PSA Response Evaluable Set: Included all participants that were enrolled, received at least 1 dose of acapatamab/AMG 404, had measurable (i.e., > 0) baseline PSA and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 1 Day 1 to 5 months post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
|
||||||||||||||||||||||||||||||||
Notes [16] - 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC0 Response | ||||||||||||||||||||
End point description |
Duration of CTC0 response was defined as the time from the date of initial CTC0 response to the earlier of CTC0 progression or death. Participants who had not ended their response at the time of analysis had duration of CTC0 response censored on the date of their last CTC0 or CTC conversion assessment.
Duration of CTC0 was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From date of initial CTC0 response to the earlier of CTC0 progression or death (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [17] - Duration of CTC0 response was not calculable. [18] - Duration of CTC0 response was not calculable. [19] - Duration of CTC0 response was not calculable. [20] - Duration of CTC0 response was not calculable. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Duration of PSA Response | ||||||||||||||||||||
End point description |
Duration of PSA response was defined as the time of an initial PSA response (PSA 50) to the earlier of PSA progression or death. Participants who had not ended their response at the time of analysis had duration of PSA response censored on the date of their last PSA measurement.
Duration of PSA response was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From date of an initial PSA response (PSA 50) to the earlier of PSA progression or death (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [21] - Duration of PSA response was not calculable. [22] - Duration of PSA response was not calculable. [23] - Duration of PSA response was not calculable. [24] - Duration of PSA response was not calculable. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC Conversion Response | ||||||||||||||||||||
End point description |
Duration of CTC conversion response was defined as the time from the date of an initial CTC conversion response to the earlier of CTC conversion progression or death. Participants who had not ended their response at the time of analysis had duration of CTC response censored on the date of their last CTC0 or CTC conversion assessment.
Duration of CTC conversion response was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From the date of an initial CTC conversion response to the earlier of CTC conversion progression or death (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [25] - Duration of CTC conversion response was not calculable. [26] - Duration of CTC conversion response was not calculable. [27] - Duration of CTC conversion response was not calculable. [28] - Duration of CTC conversion response was not calculable. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Duration of Response per RECIST 1.1 | ||||||||||||||||||||
End point description |
Duration of response per RECIST 1.1 was defined as the time from the date of an initial objective response (CR/PR) per RECIST 1.1 to the earlier of soft-tissue progression per RECIST 1.1 or death. CR/PR must have been confirmed at least 4 weeks later. Participants who had not ended their response at the time of analysis had duration of response censored at their last evaluable tumor assessment by computed tomography (CT)/magnetic resonance imaging (MRI) scan.
Duration of response was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From date of an initial objective response per RECIST 1.1 to the earlier of soft-tissue progression per RECIST 1.1 or death (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [29] - Duration of response was not calculable. [30] - Duration of response was not calculable. [31] - Duration of response was not calculable. [32] - Duration of response was not calculable. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Radiographic Progression Free Survival (rPFS) | ||||||||||||||||||||
End point description |
rPFS was defined as the interval from study Day 1 to the earlier of a radiographic progression or death from any cause; otherwise, rPFS was censored at the last evaluable tumor assessment date. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or known, rPFS was censored at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile).
99999 = upper limit was not calculable due to low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From study Day 1 to the earlier of a radiographic progression or death from any cause (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Overall Survival (OS) | ||||||||||||||||||||
End point description |
OS was defined as the time from the date of study Day 1 until death due to any cause. OS time (months) = (date of death - study Day 1 + 1) x 12/365.25. Any participant known to have died at the time of analysis was censored based on the last recorded date on which the participant was alive. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Kalbfleisch and Prentice.
9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile).
99999 = upper limit was not calculable due to low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From the date of study Day 1 until death due to any cause (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C: PSA Progression Free Survival (PFS) | ||||||||||||||||||||
End point description |
PSA PFS was defined as the interval from study Day 1 to the earlier of a PSA progression or death from any cause; otherwise, PSA PFS was censored on the date of the last PSA measurement. If a participant had no baseline or post-baseline PSA measurement and a vital status of alive or known, PSA PFS was censored at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
99999 = upper limit was not calculable due to low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From study Day 1 to the earlier of a PSA progression or death from any cause (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Clinical PFS | ||||||||||||||||||||
End point description |
Clinical PFS was defined as the time from the first dose of acapatamab or AMG 404 (subprotocol C only) to clinical disease progression or death from any cause; otherwise, clinical PFS was censored on the date of last disease assessment. If a participant had no post-baseline disease assessment and a vital status of alive or known, clinical PFS was censored at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile).
99999 = upper limit was not calculable due to low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From first dose of acapatamab or AMG 404 (subprotocol C only) to clinical disease progression or death from any cause (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Time to Radiographic Progression | ||||||||||||||||||||
End point description |
Time to radiographic progression was defined as the interval from study Day 1 to radiographic progression in the absence of subsequent anticancer therapy. Time to radiographic progression was censored at the last evaluable post-baseline tumor assessment prior to subsequent anti-cancer therapy; otherwise at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile).
99999 = upper limit was not calculable due to low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From study Day 1 to radiographic progression in the absence of subsequent anticancer therapy (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Time to PSA Progression | ||||||||||||||||||||
End point description |
Time to PSA progression was defined as the interval from study Day 1 to PSA progression, otherwise time to PSA progression was censored at the last PSA assessment. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile).
99999 = upper limit was not calculable due to low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From study Day 1 to PSA progression (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Time to Subsequent Therapy | ||||||||||||||||||||
End point description |
Time to subsequent therapy was defined as the interval from study Day 1 to the time a participant starts/receives the subsequent cancer therapy/subsequent therapy; otherwise, time to subsequent therapy was censored at the last known date of any of the study assessments prior to initiating the subsequent cancer therapy/subsequent therapy. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile).
99999 = upper limit was not calculable due to low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From study Day 1 to the time a participant starts/receives the subsequent cancer therapy/subsequent therapy (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Percentage of Participants Who Experienced a Gallium Prostate-specific Membrane Antigen-11 (PSMA-11) Response | ||||||||||||||||||||
End point description |
A Gallium PSMA-11 response was defined as a ≥ 50% reduction from baseline in the maximum standardized update value (SUV) using 68Gallium (68Ga)-PSMA-11 positron emission tomography (PET)/CT. PSMA-11 response percentages were based on the number of participants with a baseline PSMA assessment (defined as the last non-missing value on or prior to the pre-dose of AMG 160/AMG 404 assessments) on Cycle 1 Day 1. The 95% confidence interval was calculated based on the Clopper-Pearson method.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Time to Symptomatic Skeletal Events | ||||||||||||||||||||
End point description |
Time to symptomatic skeletal events was defined as time from study Day 1 to the first symptomatic skeletal event, otherwise time to symptomatic skeletal event was censored at the last dose of acapatamab/AMG 404 or end of safety follow-up date, whichever was later. Symptomatic skeletal events included fracture, spinal cord compression and radiation or surgery to bone. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley.
9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile).
999999 = median, lower and upper limits were not calculable due to very low number of events.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From study Day 1 to the first symptomatic skeletal event (up to a maximum of 3 years).
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Total Alkaline Phosphatase Levels | ||||||||||||||||||||||||||||||
End point description |
Alkaline phosphatase levels were collected centrally.
Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [33] - End of treatment visit N = 12 [34] - End of treatment visit N = 9 [35] - End of treatment visit N = 10 [36] - End of treatment visit N = 6 |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Bone Specific Alkaline Phosphatase Levels | ||||||||||||||||||||||||||||||
End point description |
Bone specific alkaline phosphatase levels were collected centrally.
Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [37] - End of treatment visit N = 11 [38] - End of treatment visit N = 9 [39] - End of treatment visit N = 9 [40] - End of treatment visit N = 5 |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Lactate Dehydrogenase Levels | ||||||||||||||||||||||||||||||
End point description |
Lactate dehydrogenase levels were collected centrally.
Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [41] - End of treatment visit N = 11 [42] - End of treatment visit N = 9 [43] - End of treatment visit N = 10 [44] - End of treatment visit N = 6 |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Hemoglobin Levels | |||||||||||||||||||||||||||||||||||
End point description |
Hemoglobin levels were collected locally.
9999 = Data not available as data was only collected for safety-follow up visit 2 for subprotocol C.
Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
|||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.4 weeks, max AMG 404 duration = 105.1 weeks.
|
|||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||
Notes [45] - Safety follow-up visit N = 7 Safety follow-up visit 2 N = 0 [46] - Safety follow-up visit N = 7 Safety follow-up visit 2 N = 0 [47] - Safety follow-up visit N = 8 Safety follow-up visit 2 N = 6 [48] - Safety follow-up visit N = 5 Safety follow-up visit 2 N = 3 |
||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Neutrophil-to-lymphocyte Ratio | |||||||||||||||||||||||||||||||||||
End point description |
Data for the neutrophil-to-lymphocyte ratio were collected locally. Neutrophil-to-lymphocyte ratio was calculated by dividing the number of absolute neutrophils by the number of lymphocytes.
9999 = Data not available as data was only collected for safety-follow up visit 2 for subprotocol C.
Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
|||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.4 weeks, max AMG 404 duration = 105.1 weeks.
|
|||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||
Notes [49] - Safety follow-up visit N = 6 Safety follow-up visit 2 N = 0 [50] - Safety follow-up visit N = 7 Safety follow-up visit 2 N = 0 [51] - Safety follow-up visit N = 8 Safety follow-up visit 2 N = 5 [52] - Safety follow-up visit N = 5 Safety follow-up visit 2 N = 2 |
||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1, 2 and 3): Urine N-telopeptide Levels | ||||||||||||||||||||||||||||||
End point description |
Urine N-telopeptide levels were collected centrally.
Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [53] - End of treatment visit N = 10 [54] - End of treatment visit N = 4 [55] - End of treatment visit N = 7 [56] - No data was collected for participants in subprotocol C, part 3. |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Subprotocol A, B and C (Parts 1 and 2): Maximum Serum Concentration (Cmax) of Acapatamab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Serum concentrations of acapatamab were determined using a validated assay.
9999 = Data was not available due to low number of participants with available samples.
Pharmacokinetic (PK) Concentration Analysis Set: Included all participants who received acapatamab and had at least 1 PK concentration available for analysis.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [57] - Cycle 2 N = 2 [58] - Cycle 2 N = 3 [59] - Cycle 2 N = 2 [60] - Cycle 1 N = 2 [61] - Cycle 2 N = 4 [62] - Cycle 2 N = 3 [63] - Cycle 2 N = 4 [64] - Cycle 2 N = 6 [65] - Cycle 2 N = 3 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Subprotocol A. B and C (Parts 1 and 2): Area Under the Curve During a Dosing Interval (AUCtau) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Serum concentrations of acapatamab were determined using a validated assay.
9999 = Data was not available due to low number of participants with available samples.
PK Concentration Analysis Set: Included all participants who received acapatamab and had at least 1 PK concentration available for analysis.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [66] - No participants had available samples. [67] - Cycle 1 N = 1 [68] - Cycle 2 N = 1 [69] - Cycle 1 N = 2 [70] - Cycle 1 N = 0 [71] - Cycle 2 N = 2 [72] - Cycle 2 N = 4 [73] - Cycle 2 N = 4 [74] - Cycle 2 N = 3 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1 and 2): Accumulation Ratio of Acapatamab | ||||||||||||||||||||||||||||||||||||
End point description |
Serum concentrations of acapatamab were determined using a validated assay.
Accumulation ratio was not calculated due to the differences in dosing length and dosage
between the lead in dose and the target dose administrations.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days).
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [75] - Accumulation ratio was not calculated. [76] - Accumulation ratio was not calculated. [77] - Accumulation ratio was not calculated. [78] - Accumulation ratio was not calculated. [79] - Accumulation ratio was not calculated. [80] - Accumulation ratio was not calculated. [81] - Accumulation ratio was not calculated. [82] - Accumulation ratio was not calculated. |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Subprotocols A, B and C (Parts 1 and 2): Terminal half-life (t1/2z) of Acapatamab | ||||||||||||||||||||||||||||||||||||||||
End point description |
Serum concentrations of acapatamab were determined using a validated assay.
9999 = Data was not available due to low number of participants with available samples.
PK Concentration Analysis Set: Included all participants who received acapatamab and had at least 1 PK concentration available for analysis.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 2: Days 1 to 14 (each cycle was 28 days).
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Subprotocol C, Part 3: Number of Participants Who Experienced a TEAE [83] | ||||||||||
End point description |
A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment that started after the first dose of AMG 404, whichever was earlier.
A treatment-related TEAE was defined as a TEAE that had a reasonable possibility of being caused by AMG 404.
Clinically significant changes from baseline in vital signs and clinical laboratory tests were also recorded as TEAEs.
Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of AMG 404.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
From first dose of AMG 404 to the first of 30 days after last dose of AMG 404, end of study date or the initiation of a new anticancer therapy (up to a maximum of 3 years).
|
||||||||||
Notes [83] - 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: No statistical analyses were pre-planned for this endpoint. |
|||||||||||
|
|||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Death: 1st dose of acapatamab/AMG 404 to end of study (up to a maximum of 3 years). TEAE: 1st dose of acapatamab/AMG 404 to min end of treatment + 30 days, end of study, 1st new anti-cancer therapy) (up to a maximum of 3 years)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol A: Acapatamab and Enzalutamide
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol B: Acapatamab and Abiraterone
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Subprotocol C, Part 3: AMG 404 Monotherapy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
21 Oct 2020 |
The following updates were made to the master protocol:
- Removed Appendix 3 (Safety Events: Definitions and Procedures for Recording, Evaluating, Follow-up and Reporting) as this appendix was added to all subprotocols.
- Additional changes were made to align with subprotocol amendments (removal of electrocardiograms from endpoint and “subject’s legally acceptable representative”). |
||
30 Mar 2021 |
The following updates were made to the master protocol:
- Clarified that participant randomization into subprotocols depended on upon slot availability .
- Approximate total participant enrollment was updated to align with changes made in subprotocols A, B, and C (addition of Asia cohort).
- Administrative changes and minor changes to align with protocol template were made. |
||
13 May 2021 |
The following updates were made to the master protocol:
- Included a new subprotocol ((Subprotocol D: A Phase 1b Study Evaluating the Safety and Efficacy of AMG 160 Monotherapy in Subjects With Metastatic Castration Resistant Prostate Cancer [mCRPC]). The study schema, number of participants and measures to minimize bias were updated.
- The primary endpoint was clarified to indicate that dose-limiting toxicities are only an endpoint for the dose exploration phase of associated subprotocols.
- Reference included to the master informed consent form. |
||
16 Jul 2021 |
The following updates were made to the master protocol:
- Clarified the definition of screen failures.
- Aligned with updated protocol template.
- Minor clarifications to language.
- Administrative and editorial changes throughout protocol. |
||
21 Feb 2022 |
The following updates were made:
- Study Governance Considerations were updated to include that Amgen or its designee reserved the right to stop one or multiple subprotocols in addition to the study or study site participation.
- In case tocilizumab is not available, siltuximab language was added to include
instructions for administration and conduction of a subgroup analysis of safety with
cytokine release syndrome outcome and pharmacokinetics for participants who received
siltuximab treatment.
- Since an analysis based on RECIST 1.1
without PCWG3 modifications was performed,
secondary endpoint was updated to remove PCWG3 modifications for RECIST assessment. PCWG3 recommended endpoints were also, albeit separately, evaluated.
- Anemia was added as a new hematology-related sign and symptom of cytokine release
syndrome.
- The approximate number of participants to be enrolled in subprotocols A-D was updated to
136 participants to reflect a change made in the number of participants to be enrolled for
subprotocol C (reduced to 30).
- A clarification was provided to specify that countries in Asia did not participate in
subprotocol D.
- A clarification was provided to align naming of the investigational product AMG 160 in
study protocol with the name used in Investigator’s Brochure, Acapatamab.
- Reference section was updated to add two citations supporting the newly added siltuximab language.
- Administrative and editorial changes (including grammatical, typographical, and
formatting) were made throughout the protocol. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Study 20190505 (including all subprotocols) was discontinued early after a strategic decision by Amgen. This study was not stopped for safety reasons or lack of efficacy. |