safety and efficacy of therapies for metastatic castration-resistant prostate cancer (mcrpc)

Conditions: Metastatic Castration-resistant Prostate Cancer

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).

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).

Eligibility 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

Keywords: acapatamab half-life extended (hle) bite mcrpc metastatic castration-resistant prostate cancer 68 gallium (68ga)-prostate-specific membrane antigen (psma)-11 positron emission tomography(pet)/computed tomography (ct) and 18 f-fluorodeoxyglucose (fdg) pet/ct based response evaluation bispecific t cell engager bite