Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostat… (NCT04926181) | Clinical Trial Compass
TerminatedPhase 2
Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer
Stopped: Funding
United States2 participantsStarted 2022-03-16
Plain-language 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
Who can participate
Age range18 Years
SexMALE
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Inclusion criteria
✓. Participants must have histologically confirmed prostate adenocarcinoma at the time of diagnosis, with subsequent development of metastatic castration-resistant prostate cancer. Prostate adenocarcinoma with neuroendocrine features (e.g. positive chromogranin and/or synaptophysin expression by IHC) is allowed.
✓. Evidence of disease progression (PD) by PSA and/or radiographic progression by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria at the time of study entry.
✓. Prior progression on at least one androgen signaling inhibitor (e.g. abiraterone acetate, apalutamide, enzalutamide, darolutamide ). Treatment with prior androgen signaling inhibitor may have been initiated in either the castration-sensitive prostate cancer (CSPC) and/or CRPC setting.
✓. Patients must be evaluable for the primary endpoint of composite response and must have either serum Prostate-specific antigen (PSA) \> 2 ng/mL during screening and/or measurable disease by RECIST 1.1 criteria.
✓. Participants must have clinicogenomic evidence of treatment emergent small cell neuroendocrine prostate cancer as defined by one or more of the following:
✓. Histologic evidence of small cell neuroendocrine prostate cancer on evaluation of castrate resistant prostate cancer (CRPC) tissue by centralized pathology review and/or
✓. Presence of loss-of-function mutation or deletion of Retinoblastoma (RB1) gene on a Clinical Laboratory Improvement Amendments (CLIA)-approved genomic-sequencing platform. Either monoallelic or biallelic mutations in RB1 are allowed.
✓. No more than one prior line of taxane-based chemotherapy administered in the metastatic castrate resistant prostate cancer (mCRPC) setting. Chemotherapy administered in the castration-sensitive setting does not count towards this limit. Prior carboplatin is allowed and does not count as an additional line of therapy when given in conjunction with taxane.
Exclusion criteria
✕. De novo small cell carcinoma of the prostate.
✕. Has participated in a study of an investigational product and received study treatment or used an investigational device other than those specified in the protocol within 2 weeks of C1D1.
✕. Hypersensitivity to cetrelimab, apalutamide, or any of its excipients.
✕. Has received prior radiotherapy within 2 weeks of C1D1. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
✕. Receipt of prior cetrelimab or another immune checkpoint inhibitor targeting PD-1/PD-L1 and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (e.g. pembrolizumab, nivolumab, ipilimumab). Prior treatment with sipuleucel-T is allowed.
✕. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients on low dose oral weekly methotrexate are allowed. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or treatment with drugs (e.g. methimazole, neomercazole, carbimazole, etc.) that function to decrease the generation of thyroid hormone by a hyper-functioning thyroid gland (e.g., in Graves' disease) is not considered a form of systemic treatment of an autoimmune disease.
✕. Individuals with concurrent second malignancy requiring active treatment at study entry that could affect safety or efficacy endpoints. Non-melanoma skin cancer, non-muscle invasive bladder cancer, and other carcinomas-in-situ are allowable exceptions.