Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
- Interventional
- Recruiting
- NCT04631601
Contact Information
A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
This is a master protocol designed to evaluate the safety and efficacy of investigational therapies in participants with metastatic castration-resistant prostate cancer (mCRPC).
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).
Gender
Male
Age Group
18 Years to 99 Years
Accepting Healthy Volunteers?
No
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
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