Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

Sponsor

Amgen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04631601

Collaborator

(none)

136

Enrollment

Locations

Arms

54.4

Anticipated Duration (Months)

9.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a master protocol designed to evaluate the safety and efficacy of investigational therapies in participants with metastatic castration-resistant prostate cancer (mCRPC).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Drug: Acapatamab Drug: Enzalutamide Drug: Abiraterone Drug: AMG 404	Phase 1/Phase 2

Detailed Description

This is a master protocol designed to evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and efficacy of Acapatamab, in combination with enzalutamide, abiraterone, or the PD1 inhibitor AMG 404, AMG 404 monotherapy, as well as Acapatamab monotherapy, in participants with metastatic castration-resistant prostate cancer (mCRPC).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

136 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 15, 2021

Anticipated Primary Completion Date :

Jan 27, 2023

Anticipated Study Completion Date :

Jul 28, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acapatamab and Enzalutamide: Dose Exploration The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: Enzalutamide Enzalutamide will be administered orally. Other Names: Androgen receptor inhibitor
Experimental: Acapatamab and Enzalutamide: Dose Expansion Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with enzalutamide.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: Enzalutamide Enzalutamide will be administered orally. Other Names: Androgen receptor inhibitor
Experimental: Acapatamab and Abiraterone: Dose Exploration The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: Abiraterone Abiraterone will be administered orally. Other Names: Cytochrome P450 (CYP)17 inhibitor
Experimental: Acapatamab and Abiraterone: Dose Expansion Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with abiraterone.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: Abiraterone Abiraterone will be administered orally. Other Names: Cytochrome P450 (CYP)17 inhibitor
Experimental: Acapatamab and AMG 404: Dose Exploration The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: AMG 404 AMG 404 will be administered as an intravenous (IV) infusion. Other Names: PD-1 inhibitor
Experimental: Acapatamab and AMG 404: Dose Expansion Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with AMG 404.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: AMG 404 AMG 404 will be administered as an intravenous (IV) infusion. Other Names: PD-1 inhibitor
Active Comparator: AMG 404 Monotherapy AMG 404 monotherapy is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population.	Drug: AMG 404 AMG 404 will be administered as an intravenous (IV) infusion. Other Names: PD-1 inhibitor
Experimental: Acapatamab and Enzalutamide: Dose Expansion Asia Cohort Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with enzalutamide for subjects in Asia.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: Enzalutamide Enzalutamide will be administered orally. Other Names: Androgen receptor inhibitor
Experimental: Acapatamab and Abiraterone: Dose Expansion Asia Cohort Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with abiraterone for subjects in Asia.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: Abiraterone Abiraterone will be administered orally. Other Names: Cytochrome P450 (CYP)17 inhibitor
Experimental: Acapatamab and AMG 404: Dose Expansion Asia Cohort Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with AMG 404 for subjects in Asia.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy Drug: AMG 404 AMG 404 will be administered as an intravenous (IV) infusion. Other Names: PD-1 inhibitor
Experimental: Acapatamab Monotherapy Acapatamab monotherapy is being conducted to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Acapatamab in subjects with mCRPC.	Drug: Acapatamab Acapatamab will be administered as an intravenous (IV) infusion. Other Names: PSMA targeted therapy

Outcome Measures

Primary Outcome Measures

Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs) [Up to 3 years]
The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab. The analysis of dose-limiting toxicity (DLT) will be conducted on the DLT Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab with an evaluable DLT endpoint. If a single subject experiences more than 1 DLT it will be counted as 1. The DLT endpoint is evaluable if either: 1) the subject experiences a DLT; or 2) the subject does not experience a DLT after receiving all planned doses within the 28-day DLT window in cycle 1.
Number of participants who experience one or more treatment-emergent adverse events (TEAEs) [Up to 3 years]
Number of participants who experience one or more treatment-related adverse events [Up to 3 years]
Number of participants who experience a clinically significant change in vital signs [Up to 3 years]
Number of participants who experience a clinically significant change in clinical laboratory tests [Up to 3 years]

Secondary Outcome Measures

Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications [Up to 3 years]
Number of participants who experience circulating tumor cell (CTC) response [Up to 3 years]
Number of participants who experience prostate-specific antigen (PSA) response rate [Up to 3 years]
Duration of response [Up to 3 years]
Overall survival (OS) [Up to 3 years]
Progression-free survival [Up to 3 years]
Time to progression [Up to 3 years]
Time to subsequent therapy [Up to 3 years]
Maximum plasma concentration (Cmax) [Up to 3 years]
Minimum plasma concentration (Cmin) [Up to 3 years]
Area under the concentration-time curve (AUC) [Up to 3 years]
Accumulation ratio based on area under the concentration-time curve (AUC) [Up to 3 years]
Half-life (t1/2) [Up to 3 years]
Change from baseline in prostate-specific membrane antigen (PSMA)-positive tumor burden assessed using gallium (GA) 68-labelled PSMA-11 positron emission tomography/computed tomography (PET/CT) [Baseline up to 3 years]
Change from baseline in prostate-specific membrane antigen (PSMA)-negative disease burden assessed using 18F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) [Baseline to 3 years]
Time to symptomatic skeletal events [Up to 3 years]
Concentration of alkaline phosphatase [Up to 3 years]
Concentration of lactate dehydrogenase (LDH) [Up to 3 years]
Concentration of hemoglobin [Up to 3 years]
Neutrophil-to-lymphocyte ratio [Up to 3 years]
Concentration of N-telopeptide in the urine [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

All parts

Inclusion Criteria:

≥ 18 years of age (or legal adult age within country)
Subject has provided informed consent prior to initiation of any study-specific activities/procedures
Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate
Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist (testosterone ≤ 50 ng/dL (or 1.7 nmol/L))

Exclusion Criteria:

Central nervous system (CNS) metastases or leptomeningeal disease
History or presence of clinically relevant CNS pathology
Confirmed history or current autoimmune disease or other diseases requiring permanent immunosuppressive therapy
Myocardial infarction, uncontrolled hypertension, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months
Prior treatment with a taxane for mCRPC
Major surgery and/or Radiation within 4 weeks
History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with medical monitor and meeting the following criteria:
Negative test for SARS-CoV-2 RNA by real time polymerase chain reaction (RT-PCR) within 72 hours of first dose of Acapatamab (or AMG 404 in Part 3)
No acute symptoms of COVID-19 disease within 10 days prior to first dose of Acapatamab (or AMG 404 in Part 3) (counted from day of positive test for asymptomatic subjects)

Prior/Concurrent Clinical Study Experience

Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded with the exception of investigational scans.

Subprotocol A only:

Inclusion criteria

• Subjects planning to receive enzalutamide for the first time for mCRPC

Exclusion criteria

Use of strong CYP2C8 inhibitors or strong CYP3A4 inducers
Use of narrow therapeutic index drugs that are substrates of CYP3A4, CYP2C9 or CYP2C19

Subprotocol B only:

Inclusion criteria

Subjects planning to receive abiraterone for the first time for mCRPC Exclusion criteria
Baseline moderate and severe hepatic impairment (Child-Pugh Class B and C)
Presence of uncontrolled hypertension, hypokalemia, or fluid retention
History or presence of adrenocortical insufficiency
Use of concomitant medications that are sensitive substrates for CYP2D6 with a narrow therapeutic index
Use of strong CYP3A4 inducers

Subprotocol C only:

Inclusion criteria

Subjects who are refractory to a novel antiandrogen therapy. Subjects must be ineligible for or refuse taxane therapy.
Evidence of progressive disease, defined as 1 or more PCWG3 criteria: PSA level >/=1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart, nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications, and/or appearance of 2 or more new lesions in bone scan Exclusion criteria
History or evidence of interstitial lung disease or active, non-infectious pneumonitis
Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a grade 3 or higher immune-related adverse event prior to first day of dose

Subprotocol D only:

Inclusion criteria

Subjects may have had novel hormonal therapies (NHT; eg, abiraterone, enzalutamide, apalutamide, or darolutamide) for prostate cancer, but no more than 1 NHT for metastatic prostate cancer
Ineligible for or refuse taxane therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of California at Irvine Medical Center	Orange	California	United States	92868
3	University of California San Francisco Mission Bay Campus	San Francisco	California	United States	94158
4	University of Chicago	Chicago	Illinois	United States	60637
5	Norton Cancer Institute	Louisville	Kentucky	United States	40207
6	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
7	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
8	St Vincents Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
9	Rigshospitalet	Kobenhavn O		Denmark	2100
10	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
11	Skanes universitetssjukhus	Lund		Sweden	221 85
12	Karolinska Universitetssjukhuset Solna	Stockholm		Sweden	171 76
13	Akademiska sjukhuset	Uppsala		Sweden	75185
14	Royal Marsden Hospital	Sutton		United Kingdom	SM2 5PT