Download PDF

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

20190505

ISRCTN number

US NCT number

NCT04631601

WHO universal trial number (UTN)

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

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

23 Oct 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 Oct 2023

Was the trial ended prematurely?

Yes

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

Independent data monitoring committee (IDMC) involvement?

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

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

Top of page

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.

Screening details

A total of 54 participants were enrolled and 53 received study treatment.

Period 1 title

Main Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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.

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.

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.

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.

Number of subjects in period 1	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Started	14	15	15	10
Received study treatment	14	14	15	10
Completed	1	0	2	5
Not completed	13	15	13	5
Adverse event, serious fatal	4	5	8	2
Consent withdrawn by subject	2	-	-	1
Lost to follow-up	-	1	-	-
Decision by sponsor	7	9	5	2

Baseline characteristics

Top of page

Reporting group title

Subprotocol A: Acapatamab and Enzalutamide

Reporting group description

Reporting group title

Subprotocol B: Acapatamab and Abiraterone

Reporting group description

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.

Reporting group values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy	Total
Number of subjects	14	15	15	10	54
Age Categorical
Units: Subjects
Adults (18-64 years)	3	7	4	2	16
From 65-84 years	11	8	11	8	38
Age Continuous
Units: years
arithmetic mean (standard deviation)	68.43 ( 4.83 )	64.5 ( 8.6 )	68.47 ( 9.33 )	64.40 ( 9.94 )	-
Gender Categorical
Units: Subjects
Female	0	0	0	0	0
Male	14	15	15	10	54
Ethnicity
Units: Subjects
Hispanic/Latino	0	2	0	0	2
Not Hispanic/Latino	14	13	15	10	52
Race
Units: Subjects
Asian	0	0	1	0	1
Black or African American	0	0	0	1	1
White	14	14	14	9	51
Other	0	1	0	0	1

End points

Top of page

Reporting group title

Subprotocol A: Acapatamab and Enzalutamide

Reporting group description

Reporting group title

Subprotocol B: Acapatamab and Abiraterone

Reporting group description

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

Subject analysis set title

Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Subprotocol B (Cohort 1): Acapatamab and Abiraterone

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Subprotocol B (Cohort 2): Acapatamab and Abiraterone

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone

Subject analysis set type

Full analysis

Subject analysis set description

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.

Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

Top of page

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.

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
Number of subjects analysed	14	13	15
Units: participants	3	1	6

No statistical analyses for this end point

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response

Top of page

End point title

Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response ^[3] ^[4]

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
[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.

End point values	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	5
Units: percentage of participants
number (confidence interval 95%)	20.0 (0.51 to 71.64)

No statistical analyses for this end point

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response

Top of page

End point title

Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response ^[5] ^[6]

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
[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.

End point values	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	3
Units: percentage of participants
number (confidence interval 95%)	0.0 (0.00 to 70.76)

No statistical analyses for this end point

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response

Top of page

End point title

Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response ^[7] ^[8]

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
[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.

End point values	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	10
Units: percentage of participants
number (confidence interval 95%)
PSA 30 Response	20.0 (2.52 to 55.61)
PSA 50 Response	20.0 (2.52 to 55.61)
PSA 70 Response	10.0 (0.25 to 44.50)
PSA 90 Response	10.0 (0.25 to 44.50)

No statistical analyses for this end point

Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

Top of page

End point title

Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) ^[9] ^[10]

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
[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.

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
Number of subjects analysed	14	14	15
Units: participants
At least 1 TEAE	14	14	15
At least 1 treatment-related TEAE	14	14	15

No statistical analyses for this end point

Primary: Subprotocol C, Part 3: Objective Response Rate (ORR)

Top of page

End point title

Subprotocol C, Part 3: Objective Response Rate (ORR) ^[11] ^[12]

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
[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.

End point values	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	6
Units: percentage of participants
number (confidence interval 95%)	0 (0.00 to 45.93)

No statistical analyses for this end point

Secondary: Subprotocols A. B and C (Parts 1 and 2): ORR

Top of page

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.

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
Number of subjects analysed	2	5	7
Units: percentage of participants
number (confidence interval 95%)	50.0 (1.26 to 98.74)	40.0 (5.27 to 85.34)	14.3 (0.36 to 57.87)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC Conversion Response

Top of page

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.

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
Number of subjects analysed	8	5	3
Units: percentage of participants
number (confidence interval 95%)	75.0 (34.91 to 96.81)	100.0 (47.82 to 100.00)	66.7 (9.43 to 99.16)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC0 Response

Top of page

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.

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
Number of subjects analysed	11	6	5
Units: percentage of participants
number (confidence interval 95%)	63.6 (30.79 to 89.07)	16.7 (0.42 to 64.12)	60.0 (14.66 to 94.73)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC0 Response

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	0 ^[16]	0 ^[17]	0 ^[18]	0 ^[19]
Units: months
median (confidence interval 95%)	( to )	( to )	( to )	( to )

Notes
[16] - Duration of CTC0 response was not calculable.
[17] - Duration of CTC0 response was not calculable.
[18] - Duration of CTC0 response was not calculable.
[19] - Duration of CTC0 response was not calculable.

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a PSA Response

Top of page

End point title

Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a PSA Response ^[20]

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
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses were pre-planned for this endpoint.

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
Number of subjects analysed	14	14	15
Units: percentage of participants
number (confidence interval 95%)
PSA 30 Response	71.4 (41.90 to 91.61)	50.0 (23.04 to 76.96)	33.3 (11.82 to 61.62)
PSA 50 Response	71.4 (41.90 to 91.61)	42.9 (17.66 to 71.14)	26.7 (7.79 to 55.10)
PSA 70 Response	64.3 (35.14 to 87.24)	35.7 (12.76 to 64.86)	20.0 (4.33 to 48.09)
PSA 90 Response	64.3 (35.14 to 87.24)	21.4 (4.66 to 50.80)	13.3 (1.66 to 40.46)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of Response per RECIST 1.1

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	0 ^[21]	0 ^[22]	0 ^[23]	0 ^[24]
Units: months
median (confidence interval 95%)	( to )	( to )	( to )	( to )

Notes
[21] - Duration of response was not calculable.
[22] - Duration of response was not calculable.
[23] - Duration of response was not calculable.
[24] - Duration of response was not calculable.

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC Conversion Response

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	0 ^[25]	0 ^[26]	0 ^[27]	0 ^[28]
Units: months
median (confidence interval 95%)	( to )	( to )	( to )	( to )

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

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of PSA Response

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	0 ^[29]	0 ^[30]	0 ^[31]	0 ^[32]
Units: months
median (confidence interval 95%)	( to )	( to )	( to )	( to )

Notes
[29] - Duration of PSA response was not calculable.
[30] - Duration of PSA response was not calculable.
[31] - Duration of PSA response was not calculable.
[32] - Duration of PSA response was not calculable.

No statistical analyses for this end point

Secondary: Subprotocols A, B and C: PSA Progression Free Survival (PFS)

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	20.30 (3.35 to 99999)	6.31 (3.94 to 99999)	3.94 (2.37 to 10.64)	4.30 (2.76 to 99999)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Overall Survival (OS)

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	9999 (10.97 to 9999)	21.75 (13.17 to 99999)	16.82 (12.06 to 99999)	9999 (0.33 to 9999)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Radiographic Progression Free Survival (rPFS)

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	18.20 (10.97 to 99999)	8.51 (3.71 to 99999)	9999 (2.00 to 9999)	3.48 (1.61 to 99999)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Clinical PFS

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	20.30 (10.97 to 99999)	15.93 (6.31 to 99999)	15.67 (7.20 to 99999)	9999 (3.71 to 9999)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Radiographic Progression

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	9999 (11.27 to 9999)	8.51 (3.71 to 99999)	9999 (2.00 to 9999)	3.48 (1.61 to 99999)

No statistical analyses for this end point

Secondary: 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

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	9	10	13	9
Units: percentage of participants
number (confidence interval 95%)	66.7 (29.93 to 92.51)	20.0 (2.52 to 55.61)	23.1 (5.04 to 53.81)	0.0 (0.00 to 33.63)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Subsequent Therapy

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	16.39 (8.84 to 20.07)	23.52 (5.98 to 99999)	9999 (4.40 to 9999)	9999 (0.89 to 9999)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to PSA Progression

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	9999 (5.09 to 9999)	4.83 (2.99 to 99999)	3.94 (2.37 to 99999)	4.30 (2.76 to 99999)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Symptomatic Skeletal Events

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14	14	15	10
Units: months
median (confidence interval 95%)	9999 (13.50 to 9999)	999999 (999999 to 999999)	999999 (999999 to 999999)	999999 (999999 to 999999)

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Total Alkaline Phosphatase Levels

Top of page

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).

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14 ^[33]	13 ^[34]	15 ^[35]	10 ^[36]
Units: U/L
arithmetic mean (standard deviation)
Baseline	198.21 ( 264.79 )	305.85 ( 356.76 )	179.00 ( 221.12 )	167.70 ( 219.41 )
End of Treatment Visit	180.00 ( 198.27 )	329.11 ( 425.58 )	133.70 ( 106.41 )	398.50 ( 627.04 )

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

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Lactate Dehydrogenase Levels

Top of page

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

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	13 ^[37]	13 ^[38]	14 ^[39]	9 ^[40]
Units: U/L
arithmetic mean (standard deviation)
Baseline	209.54 ( 62.41 )	268.54 ( 117.29 )	241.50 ( 149.98 )	267.89 ( 263.29 )
End of Treatment Visit	261.18 ( 134.21 )	210.11 ( 24.15 )	177.00 ( 40.70 )	238.50 ( 77.06 )

Notes
[37] - End of treatment visit N = 11
[38] - End of treatment visit N = 9
[39] - End of treatment visit N = 10
[40] - End of treatment visit N = 6

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Bone Specific Alkaline Phosphatase Levels

Top of page

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

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	13 ^[41]	12 ^[42]	15 ^[43]	10 ^[44]
Units: ug/L
arithmetic mean (standard deviation)
Baseline	56.85 ( 109.65 )	96.29 ( 129.56 )	44.37 ( 68.69 )	27.89 ( 30.24 )
End of Treatment Visit	35.31 ( 55.21 )	103.42 ( 165.94 )	29.44 ( 34.98 )	145.76 ( 238.81 )

Notes
[41] - End of treatment visit N = 11
[42] - End of treatment visit N = 9
[43] - End of treatment visit N = 9
[44] - End of treatment visit N = 5

No statistical analyses for this end point

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Hemoglobin Levels

Top of page

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.

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14 ^[45]	14 ^[46]	15 ^[47]	10 ^[48]
Units: g/L
arithmetic mean (standard deviation)
Baseline	123.70 ( 18.98 )	125.01 ( 12.45 )	116.51 ( 11.23 )	122.77 ( 12.96 )
Safety Follow-up Visit	123.15 ( 22.45 )	115.21 ( 13.71 )	102.34 ( 13.82 )	121.50 ( 12.81 )
Safety Follow-up Visit 2	9999 ( 9999 )	9999 ( 9999 )	106.86 ( 21.41 )	112.00 ( 12.12 )

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

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Neutrophil-to-lymphocyte Ratio

Top of page

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

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	14 ^[49]	14 ^[50]	15 ^[51]	10 ^[52]
Units: ratio
arithmetic mean (standard deviation)
Baseline	4.74 ( 3.03 )	4.93 ( 4.94 )	4.04 ( 2.90 )	4.40 ( 2.93 )
Safety Follow-up Visit	2.41 ( 1.66 )	2.44 ( 1.14 )	2.72 ( 1.94 )	2.69 ( 0.82 )
Safety Follow-up Visit 2	9999 ( 9999 )	9999 ( 9999 )	4.16 ( 4.10 )	4.73 ( 2.36 )

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

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Urine N-telopeptide Levels

Top of page

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

End point values	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	11 ^[53]	9 ^[54]	11 ^[55]	0 ^[56]
Units: nmol/mmol
arithmetic mean (standard deviation)
Baseline	155.99 ( 303.45 )	88.67 ( 43.52 )	61.06 ( 111.99 )	( )
End of Treatment Visit	109.52 ( 100.17 )	160.10 ( 150.76 )	60.57 ( 70.62 )	( )

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

Secondary: Subprotocol A, B and C (Parts 1 and 2): Maximum Serum Concentration (Cmax) of Acapatamab

Top of page

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).

End point values	Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide	Subprotocol B (Cohort 1): Acapatamab and Abiraterone	Subprotocol B (Cohort 2): Acapatamab and Abiraterone	Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone	Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404	Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
Number of subjects analysed	3 ^[57]	3 ^[58]	3 ^[59]	3 ^[60]	4 ^[61]	5 ^[62]	4 ^[63]	8 ^[64]	4 ^[65]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Cycle 1	10.5 ( 7 )	7.24 ( 19 )	8.20 ( 29 )	7.83 ( 9999 )	9.30 ( 33 )	10.4 ( 55 )	8.74 ( 23 )	11.6 ( 49 )	16.4 ( 35 )
Cycle 2	51.4 ( 9999 )	21.4 ( 729 )	30.7 ( 9999 )	31.1 ( 32 )	19.5 ( 402 )	66.7 ( 35 )	38.2 ( 73 )	21.3 ( 167 )	27.8 ( 43 )

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

Secondary: Subprotocol A. B and C (Parts 1 and 2): Area Under the Curve During a Dosing Interval (AUCtau)

Top of page

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).

End point values	Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide	Subprotocol B (Cohort 1): Acapatamab and Abiraterone	Subprotocol B (Cohort 2): Acapatamab and Abiraterone	Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone	Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404	Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
Number of subjects analysed	0 ^[66]	2 ^[67]	3 ^[68]	3 ^[69]	1 ^[70]	2 ^[71]	4 ^[72]	4 ^[73]	3 ^[74]
Units: hr•ng/mL
geometric mean (geometric coefficient of variation)
Cycle 1	( )	867 ( 9999 )	906 ( 22 )	883 ( 9999 )	9999 ( 9999 )	1330 ( 9999 )	962 ( 27 )	1270 ( 72 )	1960 ( 19 )
Cycle 2	( )	5510 ( 9999 )	4400 ( 9999 )	2700 ( 39 )	291 ( 9999 )	4510 ( 9999 )	2900 ( 66 )	2490 ( 145 )	2310 ( 69 )

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

Secondary: Subprotocols A, B and C (Parts 1 and 2): Accumulation Ratio of Acapatamab

Top of page

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).

End point values	Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide	Subprotocol B (Cohort 1): Acapatamab and Abiraterone	Subprotocol B (Cohort 2): Acapatamab and Abiraterone	Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone	Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404
Number of subjects analysed	0 ^[75]	0 ^[76]	0 ^[77]	0 ^[78]	0 ^[79]	0 ^[80]	0 ^[81]	0 ^[82]
Units: ratio
geometric mean (geometric coefficient of variation)	( )	( )	( )	( )	( )	( )	( )	( )

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

Secondary: Subprotocols A, B and C (Parts 1 and 2): Terminal half-life (t1/2z) of Acapatamab

Top of page

End point title

Subprotocols A, B and C (Parts 1 and 2): Terminal half-life (t1/2z) of Acapatamab

End point description

End point type

Secondary

End point timeframe

Cycle 2: Days 1 to 14 (each cycle was 28 days).

End point values	Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide	Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide	Subprotocol B (Cohort 1): Acapatamab and Abiraterone	Subprotocol B (Cohort 2): Acapatamab and Abiraterone	Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone	Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404	Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
Number of subjects analysed	1	1	1	3	1	2	4	3	3
Units: hours
geometric mean (geometric coefficient of variation)	64.2 ( 9999 )	83.1 ( 9999 )	111 ( 9999 )	113 ( 3 )	74.4 ( 9999 )	107 ( 9999 )	98.3 ( 17 )	84.4 ( 37 )	107 ( 25 )

No statistical analyses for this end point

Secondary: Subprotocol C, Part 3: Number of Participants Who Experienced a TEAE

Top of page

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.

End point values	Subprotocol C, Part 3: AMG 404 Monotherapy
Number of subjects analysed	10
Units: participants
At least 1 TEAE	10
At least 1 treatment-related TEAE	7

No statistical analyses for this end point

Adverse events

Top of page

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 name

MedDRA

Dictionary version

26.0

Reporting group title

Subprotocol A: Acapatamab and Enzalutamide

Reporting group description

Reporting group title

Subprotocol B: Acapatamab and Abiraterone

Reporting group description

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.

Serious adverse events	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 14 (71.43%)	9 / 14 (64.29%)	11 / 15 (73.33%)	1 / 10 (10.00%)
number of deaths (all causes)	4	5	8	2
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthenia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	6 / 14 (42.86%)	4 / 14 (28.57%)	3 / 15 (20.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	14 / 14	5 / 5	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Platelet count decreased
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haematoma
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Product prescribing error
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Immune effector cell-associated neurotoxicity syndrome
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myasthenia gravis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphopenia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Uveitis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Erythema multiforme
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Subprotocol A: Acapatamab and Enzalutamide	Subprotocol B: Acapatamab and Abiraterone	Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404	Subprotocol C, Part 3: AMG 404 Monotherapy
Total subjects affected by non serious adverse events
subjects affected / exposed	14 / 14 (100.00%)	14 / 14 (100.00%)	15 / 15 (100.00%)	10 / 10 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	2	0
Vascular disorders
Embolism venous
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Flushing
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	1	1	0
Hot flush
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	1	0	1	0
Hypertension
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	3 / 15 (20.00%)	0 / 10 (0.00%)
occurrences all number	1	3	3	0
Thrombophlebitis
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Pallor
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Peripheral artery thrombosis
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Phlebitis
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Hypotension
subjects affected / exposed	3 / 14 (21.43%)	1 / 14 (7.14%)	5 / 15 (33.33%)	0 / 10 (0.00%)
occurrences all number	6	1	7	0
Surgical and medical procedures
Functional endoscopic sinus surgery
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
General disorders and administration site conditions
Facial pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Chills
subjects affected / exposed	4 / 14 (28.57%)	2 / 14 (14.29%)	8 / 15 (53.33%)	0 / 10 (0.00%)
occurrences all number	9	4	21	0
Chest pain
subjects affected / exposed	0 / 14 (0.00%)	3 / 14 (21.43%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	3	0	4
Axillary pain
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Asthenia
subjects affected / exposed	5 / 14 (35.71%)	3 / 14 (21.43%)	2 / 15 (13.33%)	2 / 10 (20.00%)
occurrences all number	13	3	4	2
Fatigue
subjects affected / exposed	5 / 14 (35.71%)	5 / 14 (35.71%)	11 / 15 (73.33%)	3 / 10 (30.00%)
occurrences all number	5	8	20	3
Pyrexia
subjects affected / exposed	4 / 14 (28.57%)	4 / 14 (28.57%)	10 / 15 (66.67%)	1 / 10 (10.00%)
occurrences all number	10	4	25	1
Peripheral swelling
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Oedema peripheral
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	3	1	5	0
Oedema
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Malaise
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	1	1	0
Localised oedema
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Injection site reaction
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Influenza like illness
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	4 / 15 (26.67%)	0 / 10 (0.00%)
occurrences all number	0	0	8	0
Generalised oedema
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Feeling hot
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Swelling
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0
Temperature regulation disorder
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	13 / 14 (92.86%)	14 / 14 (100.00%)	13 / 15 (86.67%)	0 / 10 (0.00%)
occurrences all number	90	90	58	0
Reproductive system and breast disorders
Gynaecomastia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Pelvic discomfort
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Pelvic pain
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Testicular pain
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	1	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Catarrh
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Cough
subjects affected / exposed	2 / 14 (14.29%)	2 / 14 (14.29%)	4 / 15 (26.67%)	0 / 10 (0.00%)
occurrences all number	2	8	7	0
Dysphonia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Dyspnoea
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	3 / 15 (20.00%)	1 / 10 (10.00%)
occurrences all number	2	0	3	1
Hiccups
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Hypoxia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	2	0
Nasal congestion
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0
Nasal polyps
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Pleural effusion
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Productive cough
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Pulmonary embolism
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	0	3	2	0
Rales
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Rhinitis allergic
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 15 (13.33%)	1 / 10 (10.00%)
occurrences all number	0	0	2	1
Tachypnoea
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Pneumonitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	2	0	0
Confusional state
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	0	0	2	0
Delirium
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Depressed mood
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Depression
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Insomnia
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	2	1	3	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 14 (7.14%)	7 / 14 (50.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	1	15	5	0
Aspartate aminotransferase increased
subjects affected / exposed	2 / 14 (14.29%)	4 / 14 (28.57%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	2	10	7	0
Blood bilirubin increased
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Blood creatinine increased
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	2	0	0
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Coagulation time prolonged
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Inflammatory marker increased
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
International normalised ratio increased
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Lymphocyte count decreased
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Neutrophil count decreased
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 15 (6.67%)	1 / 10 (10.00%)
occurrences all number	2	0	1	1
Platelet count decreased
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	1	0	1	0
SARS-CoV-2 antibody test positive
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
SARS-CoV-2 test positive
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	2	0	0
Transaminases increased
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	1	1	4	0
Weight decreased
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	3 / 15 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	3	3	0
Injury, poisoning and procedural complications
Radiation associated pain
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Eye contusion
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Fall
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	2 / 10 (20.00%)
occurrences all number	1	0	0	3
Congenital, familial and genetic disorders
Gilbert's syndrome
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	2	0	1	0
Sinus tachycardia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	4 / 15 (26.67%)	0 / 10 (0.00%)
occurrences all number	0	0	4	0
Sinus bradycardia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Cardiac failure
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0
Cardiac disorder
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Bradycardia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Atrial flutter
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	2	1	0
Nervous system disorders
Lethargy
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Anosmia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	3	0	0
Balance disorder
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Brain fog
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0
Dizziness
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	2 / 15 (13.33%)	1 / 10 (10.00%)
occurrences all number	0	2	2	1
Dysgeusia
subjects affected / exposed	3 / 14 (21.43%)	2 / 14 (14.29%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	4	3	3	0
Headache
subjects affected / exposed	4 / 14 (28.57%)	4 / 14 (28.57%)	5 / 15 (33.33%)	2 / 10 (20.00%)
occurrences all number	7	6	9	3
Immune effector cell-associated neurotoxicity syndrome
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	4 / 15 (26.67%)	0 / 10 (0.00%)
occurrences all number	1	0	5	0
Nervous system disorder
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Presyncope
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	2	0
Sciatica
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Sensory disturbance
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Syncope
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	1	1	0
Taste disorder
subjects affected / exposed	3 / 14 (21.43%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	3	0	1	0
Tremor
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Paraesthesia
subjects affected / exposed	4 / 14 (28.57%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	4	1	0	0
Blood and lymphatic system disorders
Microcytic anaemia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Neutropenia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Disseminated intravascular coagulation
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Anaemia
subjects affected / exposed	6 / 14 (42.86%)	1 / 14 (7.14%)	9 / 15 (60.00%)	0 / 10 (0.00%)
occurrences all number	27	1	20	0
Thrombocytopenia
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	7	1	0	0
Leukocytosis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	0 / 15 (0.00%)	2 / 10 (20.00%)
occurrences all number	2	1	0	2
Presbyacusis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Ototoxicity
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Hypoacusis
subjects affected / exposed	3 / 14 (21.43%)	3 / 14 (21.43%)	4 / 15 (26.67%)	0 / 10 (0.00%)
occurrences all number	4	3	4	0
Deafness neurosensory
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Deafness
subjects affected / exposed	3 / 14 (21.43%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	4	0	0	0
Ear pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Eye disorders
Choroidal neovascularisation
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Conjunctival haemorrhage
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Dry eye
subjects affected / exposed	3 / 14 (21.43%)	2 / 14 (14.29%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	3	2	0	0
Exfoliation syndrome
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Chorioretinopathy
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Central serous chorioretinopathy
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Cataract nuclear
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Cataract
subjects affected / exposed	3 / 14 (21.43%)	3 / 14 (21.43%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	5	3	3	0
Blepharitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Astigmatism
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Angle closure glaucoma
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Age-related macular degeneration
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Eye pain
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	1	2	1	0
Vision blurred
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	0	2	2	0
Retinal exudates
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Retinal degeneration
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Pseudophakia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0
Presbyopia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Myopia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Keratitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Eyelid ptosis
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	1	1	0
Visual acuity reduced
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Visual impairment
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Vitreous detachment
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Uveitis
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	2	1	1	0
Gastrointestinal disorders
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Abdominal distension
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Abdominal pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	0	0	4	0
Constipation
subjects affected / exposed	3 / 14 (21.43%)	3 / 14 (21.43%)	6 / 15 (40.00%)	1 / 10 (10.00%)
occurrences all number	10	3	7	1
Diarrhoea
subjects affected / exposed	3 / 14 (21.43%)	8 / 14 (57.14%)	10 / 15 (66.67%)	2 / 10 (20.00%)
occurrences all number	5	14	23	3
Dry mouth
subjects affected / exposed	2 / 14 (14.29%)	3 / 14 (21.43%)	7 / 15 (46.67%)	0 / 10 (0.00%)
occurrences all number	3	4	10	0
Dyspepsia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	4	0	1	0
Eructation
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Vomiting
subjects affected / exposed	3 / 14 (21.43%)	5 / 14 (35.71%)	9 / 15 (60.00%)	0 / 10 (0.00%)
occurrences all number	3	8	18	0
Proctalgia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	2
Nausea
subjects affected / exposed	4 / 14 (28.57%)	3 / 14 (21.43%)	8 / 15 (53.33%)	2 / 10 (20.00%)
occurrences all number	5	14	15	2
Haemorrhoids
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Hepatobiliary disorders
Drug-induced liver injury
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Hypertransaminasaemia
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	1	0	0
Skin and subcutaneous tissue disorders
Decubitus ulcer
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Dermal cyst
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Dermatitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Dry skin
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	2	0	1	0
Eczema
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	1	0	0
Hyperhidrosis
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Miliaria
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Night sweats
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	1	0	1
Pruritus
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	0	3	2	0
Rash
subjects affected / exposed	3 / 14 (21.43%)	3 / 14 (21.43%)	1 / 15 (6.67%)	1 / 10 (10.00%)
occurrences all number	4	3	1	1
Rash maculo-papular
subjects affected / exposed	2 / 14 (14.29%)	2 / 14 (14.29%)	4 / 15 (26.67%)	0 / 10 (0.00%)
occurrences all number	5	3	7	0
Urticaria
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0
Acute kidney injury
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0
Bladder spasm
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Calculus urethral
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Haematuria
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	2	0	1	0
Nephrolithiasis
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Pollakiuria
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	1	0	1	0
Renal colic
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	2	0	0
Urinary incontinence
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	4	0	0	0
Urinary retention
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 15 (13.33%)	1 / 10 (10.00%)
occurrences all number	0	0	3	1
Hydronephrosis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal and connective tissue disorders
Groin pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Arthralgia
subjects affected / exposed	3 / 14 (21.43%)	2 / 14 (14.29%)	0 / 15 (0.00%)	2 / 10 (20.00%)
occurrences all number	3	3	0	3
Arthritis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Back pain
subjects affected / exposed	2 / 14 (14.29%)	4 / 14 (28.57%)	5 / 15 (33.33%)	1 / 10 (10.00%)
occurrences all number	3	7	7	1
Bone pain
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Flank pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Fracture pain
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Immune-mediated arthritis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Muscular weakness
subjects affected / exposed	3 / 14 (21.43%)	1 / 14 (7.14%)	1 / 15 (6.67%)	1 / 10 (10.00%)
occurrences all number	4	1	1	2
Musculoskeletal chest pain
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Myalgia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	1	0	2	0
Neck pain
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	1	2	1	0
Osteonecrosis of jaw
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Pain in extremity
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	1 / 15 (6.67%)	1 / 10 (10.00%)
occurrences all number	0	1	1	1
Pain in jaw
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Muscle spasms
subjects affected / exposed	0 / 14 (0.00%)	3 / 14 (21.43%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	3	1	0
Infections and infestations
Urinary tract infection bacterial
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	1	0	0
Abscess
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Bacteraemia
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
COVID-19
subjects affected / exposed	4 / 14 (28.57%)	1 / 14 (7.14%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	4	1	1	0
Herpes simplex reactivation
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	0	0	2	0
Urinary tract infection
subjects affected / exposed	3 / 14 (21.43%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	3	1	0	0
Sinusitis
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Rash pustular
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Parotitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Oral candidiasis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	2	0	2	0
Nasopharyngitis
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Mucosal infection
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	1 / 15 (6.67%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0
Influenza
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Infection
subjects affected / exposed	0 / 14 (0.00%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0
Hordeolum
subjects affected / exposed	1 / 14 (7.14%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	1	0	0
Vascular device infection
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	5 / 14 (35.71%)	3 / 14 (21.43%)	5 / 15 (33.33%)	1 / 10 (10.00%)
occurrences all number	5	3	6	1
Hypercalcaemia
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Hyperglycaemia
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	2	0	4	0
Hyperkalaemia
subjects affected / exposed	2 / 14 (14.29%)	1 / 14 (7.14%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	3	2	0	0
Hyperphosphataemia
subjects affected / exposed	0 / 14 (0.00%)	0 / 14 (0.00%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	1
Hypoalbuminaemia
subjects affected / exposed	2 / 14 (14.29%)	0 / 14 (0.00%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	3	0	6	0
Hypocalcaemia
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	5	0	1
Hypokalaemia
subjects affected / exposed	2 / 14 (14.29%)	2 / 14 (14.29%)	5 / 15 (33.33%)	0 / 10 (0.00%)
occurrences all number	2	2	7	0
Hypomagnesaemia
subjects affected / exposed	0 / 14 (0.00%)	2 / 14 (14.29%)	2 / 15 (13.33%)	0 / 10 (0.00%)
occurrences all number	0	2	3	0
Hyponatraemia
subjects affected / exposed	1 / 14 (7.14%)	2 / 14 (14.29%)	0 / 15 (0.00%)	1 / 10 (10.00%)
occurrences all number	1	2	0	1
Hypophosphataemia
subjects affected / exposed	2 / 14 (14.29%)	2 / 14 (14.29%)	4 / 15 (26.67%)	0 / 10 (0.00%)
occurrences all number	2	5	5	0
Malnutrition
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0
Dehydration
subjects affected / exposed	1 / 14 (7.14%)	0 / 14 (0.00%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

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.

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.

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.

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

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

Clinical trials

Clinical Trial Results: A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response

Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response

Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

Primary: Subprotocol C, Part 3: Objective Response Rate (ORR)

Primary: Subprotocol C, Part 3: Objective Response Rate (ORR)

Secondary: Subprotocols A. B and C (Parts 1 and 2): ORR

Secondary: Subprotocols A. B and C (Parts 1 and 2): ORR

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC Conversion Response

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC Conversion Response

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC0 Response

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC0 Response

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC0 Response

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC0 Response

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a PSA Response

Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a PSA Response

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of Response per RECIST 1.1

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of Response per RECIST 1.1

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC Conversion Response

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC Conversion Response

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of PSA Response

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of PSA Response

Secondary: Subprotocols A, B and C: PSA Progression Free Survival (PFS)

Secondary: Subprotocols A, B and C: PSA Progression Free Survival (PFS)

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Overall Survival (OS)

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Overall Survival (OS)

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Radiographic Progression Free Survival (rPFS)

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Radiographic Progression Free Survival (rPFS)

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Clinical PFS

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Clinical PFS

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Radiographic Progression

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Radiographic Progression

Secondary: 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

Secondary: 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

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Subsequent Therapy

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Subsequent Therapy

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to PSA Progression

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to PSA Progression

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Symptomatic Skeletal Events

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Symptomatic Skeletal Events

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Total Alkaline Phosphatase Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Total Alkaline Phosphatase Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Lactate Dehydrogenase Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Lactate Dehydrogenase Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Bone Specific Alkaline Phosphatase Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Bone Specific Alkaline Phosphatase Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Hemoglobin Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Hemoglobin Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Neutrophil-to-lymphocyte Ratio

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Neutrophil-to-lymphocyte Ratio

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Urine N-telopeptide Levels

Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Urine N-telopeptide Levels

Secondary: Subprotocol A, B and C (Parts 1 and 2): Maximum Serum Concentration (Cmax) of Acapatamab

Secondary: Subprotocol A, B and C (Parts 1 and 2): Maximum Serum Concentration (Cmax) of Acapatamab

Secondary: Subprotocol A. B and C (Parts 1 and 2): Area Under the Curve During a Dosing Interval (AUCtau)

Secondary: Subprotocol A. B and C (Parts 1 and 2): Area Under the Curve During a Dosing Interval (AUCtau)

Secondary: Subprotocols A, B and C (Parts 1 and 2): Accumulation Ratio of Acapatamab

Secondary: Subprotocols A, B and C (Parts 1 and 2): Accumulation Ratio of Acapatamab

Secondary: Subprotocols A, B and C (Parts 1 and 2): Terminal half-life (t1/2z) of Acapatamab

Secondary: Subprotocols A, B and C (Parts 1 and 2): Terminal half-life (t1/2z) of Acapatamab

Secondary: Subprotocol C, Part 3: Number of Participants Who Experienced a TEAE

Secondary: Subprotocol C, Part 3: Number of Participants Who Experienced a TEAE

Adverse events

Adverse events

Clinical Trial Results:
A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)