690TiP A phase III, randomized, double-blind trial of nivolumab or placebo combined with docetaxel for metastatic castration-resistant prostate cancer (mCRPC; CheckMate 7DX)

Abstract

Treatment with docetaxel, a recommended first-line chemotherapy for mCRPC, may enhance antitumor immune responses by (1) increasing neoantigen presentation, (2) stimulating proinflammatory cytokine secretion, and (3) downregulating suppressive immune cell populations. Immunotherapy may augment these effects, providing a strong rationale for combining immune checkpoint blockade with docetaxel in patients with mCRPC. In support of this hypothesis, the phase 2 CheckMate 9KD trial showed that combining the anti–PD-1 antibody nivolumab with docetaxel had promising clinical activity in patients with mCRPC. In this randomized, double-blind phase III trial (CheckMate 7DX), we will evaluate the combination of nivolumab plus docetaxel versus placebo plus docetaxel for men with mCRPC (NCT04100018). Key inclusion criteria are histologically confirmed adenocarcinoma of the prostate with current evidence of metastatic disease, ECOG performance status 0–1, ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analogue or bilateral orchiectomy, documented progression per PCWG3 criteria within 6 months before screening, no prior chemotherapy in the mCRPC setting, 1–2 prior second-generation hormonal therapies, and available tumor tissue for biomarker analysis. Key exclusion criteria are active brain metastases, conditions requiring systemic corticosteroid/immunosuppressive treatment, autoimmune disease, and prior treatment targeting T-cell co-stimulation or checkpoint pathways. Patients are randomized 1:1 to nivolumab + docetaxel (arm A) or placebo + docetaxel (arm B), followed by nivolumab (arm A) or placebo (arm B) alone. Docetaxel will be administered for a maximum of 10 cycles; nivolumab will be administered for a maximum of 2 years. Primary endpoints are radiographic progression-free survival per PCWG3 and overall survival. Secondary endpoints include objective response rate and duration of response per PCWG3, prostate-specific antigen response rate, safety, and pain progression (assessed by the Brief Pain Inventory-Short Form). Enrollment is ongoing with a target of 984 randomized patients. NCT04100018. Professional medical writing assistance was provided by Richard Daniel, PhD, of Parexel, funded by Bristol-Myers Squibb Company. Bristol-Myers Squibb Company.