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

Amgen

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: Abiraterone; Drug: Enzalutamide; Drug: Acapatamab; Drug: AMG 404

Study type: Interventional

Funder types: Industry

Identifiers

NCT04631601

20190505

2020-001305-23 (EudraCT Number)

Details and patient eligibility

About

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

Full 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).

Enrollment: 65 patients

Sex: Male

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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65 participants in 11 patient groups

Acapatamab and Enzalutamide: Dose Exploration

Experimental group

Description:

The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide.

Treatment:

Drug: Enzalutamide

Drug: Acapatamab

Acapatamab and Enzalutamide: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: Enzalutamide

Drug: Acapatamab

Acapatamab and Abiraterone: Dose Exploration

Experimental group

Description:

The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone.

Treatment:

Drug: Acapatamab

Drug: Abiraterone

Acapatamab and Abiraterone: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: Acapatamab

Drug: Abiraterone

Acapatamab and AMG 404: Dose Exploration

Experimental group

Description:

The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404.

Treatment:

Drug: AMG 404

Drug: Acapatamab

Acapatamab and AMG 404: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: AMG 404

Drug: Acapatamab

AMG 404 Monotherapy

Active Comparator group

Description:

AMG 404 monotherapy is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population.

Treatment:

Drug: AMG 404

Acapatamab and Enzalutamide: Dose Expansion Asia Cohort

Experimental group

Description:

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.

Treatment:

Drug: Enzalutamide

Drug: Acapatamab

Acapatamab and Abiraterone: Dose Expansion Asia Cohort

Experimental group

Description:

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.

Treatment:

Drug: Acapatamab

Drug: Abiraterone

Acapatamab and AMG 404: Dose Expansion Asia Cohort

Experimental group

Description:

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.

Treatment:

Drug: AMG 404

Drug: Acapatamab

Acapatamab Monotherapy

Experimental group

Description:

Acapatamab monotherapy is being conducted to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Acapatamab in subjects with mCRPC.

Treatment:

Drug: Acapatamab