NCT04926181

Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer

A Phase 2 Study of Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Rahul Aggarwal · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Despite the low androgen receptor (AR) transcriptional activity of treatment-emergent small cell neuroendocrine prostate cancer, there is persistent AR expression observed in the majority of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) biopsies. This indicates that epigenetic dysregulation leads to reprogramming away from an AR-driven transcriptional program. Therefore, continuation of AR blockade in the form of apalutamide may provide additive benefit compared to immune checkpoint blockade alone. The investigators hypothesize that the combination of apalutamide plus cetrelimab will achieve a clinically significant composite response rate with sufficient durability of response in mCRPC patients with evidence of treatment-emergent small cell neuroendocrine prostate cancer

Detailed description

This is a phase 2, single arm, Simon's two-stage evaluation of the combination of apalutamide plus cetrelimab in patients with mCRPC and histologic and/or genomic evidence of treatment-emergent small cell neuroendocrine prostate cancer who have previously progressed on at least one prior androgen signaling inhibitor. Participants may continue study treatment from the time of treatment initiation until confirmed radiographic progressive disease (PD) per PCWG3 and RECIST 1.1 criteria, unequivocal clinical progression, unacceptable toxicity, or patient withdrawal, whichever occurs first, for a maximum of 24 months. PRIMARY OBJECTIVE: I. To determine the composite response rate as defined by achieving one or more of the following at any time point during study treatment: 1. Decline from baseline in serum PSA of \>= 50% (PSA50), confirmed by repeat measurement \>= 4 weeks later and/or 2. Objective response by RECIST 1.1 criteria SECONDARY OBJECTIVES: I. To determine safety of the combination as determined by CTCAE version 5.0. II. To determine the median radiographic progression-free survival by PCWG3 criteria. III. To determine the PSA50 and decline from baseline in serum PSA of \>= 90% (PSA90) response proportion achieved. IV. To determine the median PSA progression-free survival. V. To determine the median overall survival. VI. To determine the objective response rate and median duration of response by RECIST 1.1 criteria. Patients will be followed up for safety evaluations 30 days and 100 days after treatment completion. Patients will be followed for overall survival every 90 days (+/- 30 days) from last dose of study treatment, until death, withdrawal of consent, or the end of the study, whichever occurs first.

Conditions

• Small Cell Neuroendocrine Carcinoma
• Prostate Cancer
• Small Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Apalutamide	240 mg once daily, for a 28 day cycle
BIOLOGICAL	Cetrelimab	480 mg given through intravenous infusion (IV) on day 1 of every 28-day treatment cycle and administered over a 60-minute infusion

Timeline

• Start date: 2022-03-16
• Primary completion: 2024-03-31
• Completion: 2024-03-31
• First posted: 2021-06-15
• Last updated: 2025-05-15
• Results posted: 2025-05-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study