Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Interventions
- Registration Number
- NCT04631601
- Lead Sponsor
- Amgen
- 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).
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 65
- ≥ 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))
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Acapatamab and AMG 404: Dose Expansion Acapatamab 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. Acapatamab and Abiraterone: Dose Expansion Asia Cohort Acapatamab 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. Acapatamab and AMG 404: Dose Expansion Asia Cohort Acapatamab 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. Acapatamab Monotherapy Acapatamab Acapatamab monotherapy is being conducted to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Acapatamab in subjects with mCRPC. Acapatamab and Enzalutamide: Dose Exploration Acapatamab The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide. Acapatamab and Enzalutamide: Dose Expansion Acapatamab 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. Acapatamab and Abiraterone: Dose Exploration Acapatamab The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone. Acapatamab and Enzalutamide: Dose Expansion Asia Cohort Acapatamab 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. Acapatamab and Abiraterone: Dose Expansion Acapatamab 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. Acapatamab and AMG 404: Dose Exploration Acapatamab The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404. Acapatamab and AMG 404: Dose Exploration AMG 404 The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404. Acapatamab and AMG 404: Dose Expansion AMG 404 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. AMG 404 Monotherapy AMG 404 AMG 404 monotherapy is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population. Acapatamab and AMG 404: Dose Expansion Asia Cohort AMG 404 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. Acapatamab and Enzalutamide: Dose Exploration Enzalutamide The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide. Acapatamab and Enzalutamide: Dose Expansion Enzalutamide 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. Acapatamab and Abiraterone: Dose Exploration Abiraterone The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone. Acapatamab and Abiraterone: Dose Expansion Abiraterone 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. Acapatamab and Enzalutamide: Dose Expansion Asia Cohort Enzalutamide 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. Acapatamab and Abiraterone: Dose Expansion Asia Cohort Abiraterone 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Duration of response Up to 3 years Overall survival (OS) Up to 3 years Progression-free survival 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 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 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 Time to progression Up to 3 years Time to subsequent therapy 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 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
Trial Locations
- Locations (14)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California at Irvine Medical Center
🇺🇸Orange, California, United States
University of California San Francisco Mission Bay Campus
🇺🇸San Francisco, California, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Rigshospitalet
🇩🇰Kobenhavn O, Denmark
St Vincents Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Skanes universitetssjukhus
🇸🇪Lund, Sweden
Karolinska Universitetssjukhuset Solna
🇸🇪Stockholm, Sweden
Akademiska sjukhuset
🇸🇪Uppsala, Sweden
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States