A Phase 2, Open-label, Study of Vobramitamab Duocarmazine in Participants With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

CP-MGC018-03

Study CP-MGC018-03 is an open-label, two-part, Phase 2 study. Part 1 of the study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT). ARAT includes abiraterone, enzalutamide, or apalutamide. Participants may have received up to 1 prior docetaxel-containing regimen, but no other chemotherapy agents. This part of the study will assess the efficacy and tolerability of vobramitamab duocarmazine (MGC018) in two experimental arms (2.0 mg/kg every 4 weeks \[Q4W\] and 2.7 mg/kg Q4W) . Approximately 100 participants will be randomized 1:1. Part 2 of the study will enroll participants with locally advanced or metastatic squamous cell carcinoma (SCC) of the anus, melanoma, head and neck squamous cell carcinoma (HNSCC), squamous non-small cell lung carcinoma (NSCLC), and small cell lung carcinoma (SCLC). Participants must have progressive following at least 1 prior line of standard chemotherapy for advanced or metastatic disease. Participants will receive vobramitamab docarmazine at a dose of 2.7 mg/kg every 4 weeks. Up to 200 participants may be enrolled in Part 2. In both parts, vobramitamab duocarmazine will be administered intravenously (IV) in clinic on Day 1 of each 4-week cycle. Vobramitamab duocarmazine will be administered for up to 26 cycles, approximately 2 years, until criteria for treatment discontinuation are met. Participants will undergo regular testing for signs of disease progression using computed tomography (CT) scans, magnetic resonance imaging (MRI), bone scans, and prostate-specific antigen (PSA) blood tests. Routine examinations and blood tests will be performed and evaluated by the study doctor.

2023-06-13

2027-05-01

2027-05-01

Active (not recruiting)

Early phase I

382

Inclusion Criteria: * Part 1 only: Histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features. * Part 2 only: Histologically confirmed SCC or the anus, melanoma, HNSCC, squamous NSCLC, or SCLC. * Part 1 only: Received 1 prior ARAT for metastatic or non-metastatic, castration-sensitive or castration-resistant prostate cancer. A second ARAT regimen of \<60 days used as bridging to lutetium-177 is permitted. * Part 2 only: At least 1 prior line of systemic therapy for unresectable or metastatic disease and no more than 2 prior lines of cytotoxic chemotherapy. Participants with HNSCC or melanoma must have received prior PD-1 or PD-L1 inhibitor for advanced or metastatic disease. * All participants must have ≥ 1 metastatic lesion, according to RECIST 1.1 or PCWG3 criteria, that is present on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan obtained ≤ 28 days prior to initiation of study treatment. * All participants must have tumor progression, according to disease-specific criteria, following their most recent anti-cancer therapy. * All participants must have and available archival or formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for participants with metastasis to internal organs * All participants have acceptable physical condition and laboratory values. * All participants of childbearing potential must agree to use highly effective methods of birth control. * All participants must not be pregnant, planning to be pregnant, or breastfeeding. Exclusion Criteria: * Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures. * Part 1 only: Received \>1 prior taxane-containing regimen for prostate cancer. A second taxane regimen of \<60 days used as bridging for lutetium-177 is permitted. * Part 1 only: Received \>3 total prior therapies for mCRPC * Part 1 only: Participants with known BRCA or ATM mutation (germline or somatic) are not eligible unless they received prior treatment with a PARP inhibitor where available, indicated and tolerated. * Another hematologic or solid tumor ≥ stage 1 malignancy that completed surgery, last dose of radiotherapy, or last dose of systemic anti-cancer therapy ≤ 2 years from first dose of study treatment. Participants who had curative therapy for non-melanomatous skin cancer or for localized malignancy are eligible. * Untreated, symptomatic central nervous system (CNS) metastasis. * Prior treatment with any B7-H3 targeted agent for cancer, * Contradictions to the use of corticosteroid treatment * Prior stem cell, tissue, or solid organ transplant. * Part 1 only: Use of products that have published anti-prostate cancer activity or are known to decrease PSA.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 382, 'type': 'ESTIMATED'}}

2024-04-09