Bristol-Myers Squibb Company announced data evaluating Opdivo (nivolumab) in combination with Yervoy (ipilimumab) in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from an interim analysis of the Phase 2 CheckMate -650 trial showed that among 32 asymptomatic or minimally symptomatic patients whose disease had progressed after second-generation hormone therapy and who had not received chemotherapy (cohort 1), with a median follow-up of 11.9 months, the objective response rate (ORR) was 25%. Additionally, among 30 patients whose disease progressed after taxane-based chemotherapy (cohort 2), with a median follow-up of 13.5 months, the ORR was 10%.
Across both cohorts, higher response rates were seen in certain patient sub-groups, including patients with high (above median) tumor mutational burden and patients with homologous recombination deficiency.
The overall safety profile was consistent with prior studies of Opdivo in combination with Yervoy with this dosing schedule. Grade three to five treatment-related adverse events occurred in 42% of patients in cohort 1 and 53% of patients in cohort 2.
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“The results from CheckMate -650 provide strong rationale for the development of combination immune checkpoint therapy for the treatment of prostate cancer, which is considered a cold tumor with few tumor-infiltrating lymphocytes,” said Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology at The University of Texas MD Anderson Cancer Center. “The clinical results from this study are encouraging and provide the foundation to test the combination strategy in a larger cohort of patients.”
“Assessing the effect of biomarkers on treatment outcomes is an important part of our ongoing multidisciplinary approach to research in translational medicine,” said Arvin Yang, M.D., Ph.D., development lead, melanoma and genitourinary cancers, Bristol-Myers Squibb. “These interim results are exciting and reinforce our commitment to identifying the patient populations most likely to derive benefit from Immuno-Oncology-based regimens across tumor types and in hard-to-treat patient populations.”
CheckMate -650 is an ongoing Phase 2 open-label trial, evaluating the safety and efficacy of Opdivo in combination with Yervoy in patients with metastatic castration-resistant prostate cancer (mCRPC). The trial includes two cohorts: asymptomatic or minimally symptomatic patients who progressed after second-generation hormone therapy and have not received chemotherapy for mCRPC; and patients who progressed after taxane-based chemotherapy. Patients received Opdivo 1 mg/kg plus Yervoy 3 mg/kg for four doses, followed by Opdivo 480 mg every four weeks. Co-primary endpoints include objective response rate (ORR) and radiographic progression-free survival (rPFS). Safety is a secondary endpoint. Exploratory endpoints include correlation of biomarkers with efficacy and prostate-specific antigen (PSA) response.
Prostate cancer is the second most frequently diagnosed cancer in men, with almost 1.28 million new cases diagnosed worldwide in 2018. Unlike many early-stage prostate cancers that need normal levels of testosterone to grow, castration-resistant prostate cancer (CRPC) continues to grow even when the amount of testosterone in the body is reduced to castrate levels. CRPC patients have a very high likelihood of having or developing metastases, meaning the cancer has spread to other areas of the body. While the five-year survival rate for most stages of prostate cancer is almost 100%, the five-year survival rate for prostate cancer that has spread to distant lymph nodes, bones or other organs is approximately 29%.