Prostate

BNT324-03 A Phase III, randomized, open-label trial of BNT324 versus docetaxel with prednisone/prednisolone in metastatic castration-resistant prostate cancer

MOA: BNT324 is an ADC composed of a anti-human B7-H3 IgG1 mAb covalently linked to a topo I inhibitor (P1021) via a tetrapeptide based cleavable linker.

Key Eligibility Criteria:

• Subjects must have histological, pathological, and/or cytological confirmation of prostate cancer that is progressive
• Subjects must have previously received at least one 1-2 prior ARPI in either non-metastatic HSPC, mHSPC, non-metastatic CRPC, or mCRPC and had progressive disease during or after at least 8 weeks of treatment
• Subjects must have ≥1 metastatic lesion
• Subjects with a positive 68Ga-PSMA-11 PET/CT scan may have received prior 177Lu-PSMA or investigational PSMA-targeted radioligand therapy if treatment was completed more than 8 weeks before trial dosing
• Subjects must have had prior orchiectomy and/or have ongoing ADT and a castrate-level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L)
• Subjects that previously received an ADC with a topoisomerase inhibitor, B7-H3 targeted therapy, or cytotoxic chemotherapy are excluded

Open-Label, Phase 1/1b Study of ORIC-944 as a Single Agent or in Combination with an Androgen Receptor Pathway Inhibitor in Patients with Metastatic Prostate Cancer (ORIC-944-01)

MOA: ORIC-944 is a highly selective, allosteric, small molecule inhibitor of PRC2 via binding the EED subunit.

Key Eligibility Criteria:

• Documented progressive metastatic prostate cancer
• Must have undergone bilateral orchiectomy or be willing to continue
  GnRH analogue or antagonist to maintain castrate levels of testosterone
• Food effect substudies: only 1 prior line of ARPI in any setting and may have received up to 1 prior line of chemo in the mHSPC setting
• Subjects with pure SCC or prostate are excluded
• Dose optimization: Received up to 1 prior line of chemotherapy in the
  mHSPC setting AND:
  • Cohorts A and B: received only one 1 prior line of abiraterone
  • Cohorts C and D: received only one 1 prior line of apalutamide, darolutamide, or enzalutamide

Randomized Phase 2b Study of ZEN003694 in Combination with Enzalutamide versus Enzalutamide Monotherapy in Patients with Metastatic Castration-Resistant Prostate Cancer (ZEN003694-201)

MOA: ZEN003694 epigenetically regulates gene expression through bromodomain and extra-terminal domain (BET) inhibition.

Key Eligibility Criteria:

• Metastatic, castration-resistant, histologically confirmed prostate cancer that has progressed on prior abiraterone treatment
• Patient must meet definition of poor responder to abiraterone by one of the following:
  • Cohort A: In HSPC setting, <12 months on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL; In CRPC setting, <6 months on abiraterone or failure to achieve a PSA50 response
  • Cohort B: In HSPC setting, ≥12 months duration on abiraterone and nadir PSA ≤ 0.2 ng/mL; In CRPC setting, ≥6 months duration on abiraterone and PSA50 response
• Subjects whose disease is not aggressive or progressing rapidly enough to prefer chemotherapy over second-line ARSI, as per investigator's opinion
• Subjects that have received second-generation androgen receptor inhibitors are excluded
• Subjects that have received prior chemotherapy in the metastatic castration-resistant setting are excluded