MGC018 Versus Androgen Receptor Axis-targeted Therapy in Participants With Metastatic Castration Resistant Prostate Cancer

• Status: Not yet recruiting
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: Male

Summary

Study CP-MGC018-03 is a randomized, open-label, seamless, Phase 2/3 study. The study will enroll participants with metastatic castration-resistant prostate cancer (mCRPC) previously treated with one prior androgen receptor axis-targeted therapy (ARAT) and one prior taxane-containing regimen. ARAT includes abiraterone, enzalutamide, or apalutamide. Participants may have received up to 1 prior cabazitaxel regimen, but no other chemotherapy agents.

The Phase 2 stage will assess efficacy and tolerability of two MGC018 experimental arms (2.0 mg/kg Q4W and 2.7 mg/kg Q4W) compared to the control arm (abiraterone or enzalutamide). Approximately 150 participants will be randomized 1:1:1 in Phase 2 among the three study treatment arms (two MGC018 experimental arms and one control arm). An interim analysis will be performed to select the Phase 3 dose regimen for the MGC018 experimental arm for Phase 3 after approximately 150 participants enrolled in Phase 2 have been followed for at least 2 months (60 days).

The Phase 3 stage will assess efficacy of the selected dose regimen for the MGC018 experimental arm versus the control arm (abiraterone or enzalutamide). Approximately 270 additional participants will be randomized 1:1 between each study treatment arm in Phase 3 (one MGC018 experimental arm and the control arm).

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MacroGenics

Criteria

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features.

• Participants must have ≥ 1 metastatic lesion that is present on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan obtained ≤ 28 days prior to initiation of study treatment.

• Tumor progression at study entry documented by PSA or imaging per PCWG3 criteria

• Received 1 prior ARAT for metastatic prostate cancer (mPC) with lack of progression for at least 12 months

• Received 1 prior taxane-containing regimen for mPC.

• May have received up to 1 prior cabazitaxel regiment for mPC.

• Availability of archival or formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for participants with metastasis to internal organs

• Acceptable physical condition and laboratory values.

Exclusion Criteria:

• Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.

• Prior chemotherapy other than docetaxel or cabazitaxel. Prior immunotherapy and radiopharmaceutical therapy is allowed.

• Known history of documented BRCA or ATM mutation (germline or somatic). Participants with known BRCA or ATM mutation who had disease progression or unacceptable toxicity on a PARP inhibitor are eligible.

• 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.