eligibility_summary
Adults (≥18) with unresectable/metastatic HER2+ mCRPC (IHC 3+/2+ or FISH+), CDK12 mutation with ERBB amplification or HER2 IHC, measurable disease, ECOG 0–2, life expectancy ≥12 weeks, prior novel AR therapy and PARP inhibitor (or platinum-resistant AVPC/NEPC), no prior HER2 therapy, adequate organ function (LVEF ≥50%). Exclude: drug allergies, recent other cancers, brain mets/meningitis, transplants, immunodeficiency, major comorbidities, active infections (HIV/HBV/HCV/TB), severe heart disease, psychiatric/substance issues, other trials.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1/2, single-arm, multi-cohort study in mCRPC with CDK12 alterations and HER2 positivity. Interventions: Disitamab vedotin (RC48), an antibody-drug conjugate targeting HER2 (ERBB2), its anti-HER2 mAb delivers the microtubule inhibitor MMAE via a cleavable linker, causing internalization, microtubule disruption, apoptosis, and bystander killing. Envafolimab, a subcutaneous anti–PD-L1 checkpoint inhibitor (single-domain antibody-Fc), blocks PD-1/PD-L1 to restore cytotoxic T-cell activity. Cohort A: RC48 + envafolimab, Cohort B: RC48 alone in chromosomal instability profiles (e.g., 11q13, MDM2/4, FGFRs amps). Targets/pathways: HER2 on tumor cells, ERBB signaling, microtubules, PD-1/PD-L1 immune checkpoint on tumor/immune cells, context of CDK12 loss (genomic instability/neoantigen load). Primary endpoint: ORR. Secondary: PSA50, PFS, OS, safety.