At a minimum follow-up of 7.9 months for the expanded cohort of patients receiving O1:Y3, the ORR was 38% (95% Confidence Interval [CI]: 28-49). For patients receiving O3:Y1, at a minimum follow-up of 38.8 months the ORR was 27% (95% CI: 19-37), and for patients receiving Opdivo alone, at a minimum follow-up of 37.7 months the ORR was 26% (95% CI: 16-37).
Median progression-free survival (PFS) and overall survival, secondary endpoints in the study, were numerically longer in the O1:Y3 treatment cohort (4.9 and 15.3 months, respectively [95% CI: 2.7-6.6 and 10.1-27.6]) compared to the O3:Y1 (2.6 and 7.4 months, respectively [95% CI: 1.4-3.9 and 5.6-11.0]) and Opdivo monotherapy (2.8 and 9.9 months, respectively [95% CI: 1.5-5.3 and 7.3-21.1]) cohorts.
These data from CheckMate -032 will be featured today in a late-breaking oral session (Presentation #LBA32) at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany.
“These results from CheckMate -032 point to the combination of nivolumab and ipilimumab as a potentially promising treatment option for patients with metastatic urothelial carcinoma who are pretreated with platinum-based chemotherapy,” said Jonathan E. Rosenberg, M.D., Chief, Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, Enno W. Ercklentz Chair, Memorial Sloan Kettering Cancer Center, New York. “These data also support the ongoing CheckMate -901 trial of the combination in patients with untreated metastatic bladder cancer, and we look forward to ongoing research to further benefit this population.”The overall safety profile was consistent with prior studies of Opdivo in combination with Yervoy with these dosing schedules. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 27%, 31% and 39% of patients treated with Opdivo monotherapy, O3:Y1 and O1:Y3, respectively; grade 5 TRAEs (pneumonitis) were observed in one patient each in the Opdivo monotherapy and O3:Y1 groups; no grade 5 TRAEs were observed in the O1:Y3 group. The combination of Opdivo plus Yervoy was also well tolerated, with 13% discontinuation rate due to TRAEs in the O1:Y3 group and 13% discontinuation rate in the O3:Y1 group. The discontinuation rate due to TRAEs in the Opdivo monotherapy group was 4%.
“The combination of Opdivo and Yervoy has shown durable efficacy across a broad range of tumor types and treatment settings, and we are equally encouraged by these data for the combination in patients living with metastatic urothelial carcinoma,” said Arvin Yang, M.D., Ph.D., development lead, melanoma and genitourinary cancers, Bristol-Myers Squibb. “We are committed to fully exploring the potential of I-O-based regimens and look forward to seeing how this important combination regimen can benefit this patient population.”
CheckMate - 032 is a multi-center, open-label Phase 1/2 trial, evaluating the safety and efficacy of Opdivo as a single agent or in combination with Yervoy in 274 patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC), RECIST v1.1 measurable disease, and ECOG performance status ≤1. Patients were heavily pretreated, with most receiving at least two prior treatment regimens. Patients received either Opdivo 3 mg/kg every two weeks (Q2W), Opdivo 3 mg/kg plus Yervoy 1 mg/kg (O3:Y1) every three weeks (Q3W) for four cycles followed by Opdivo 3 mg/kg Q2W, or Opdivo 1 mg/kg plus Yervoy 3 mg/kg Q3W for four cycles followed by Opdivo 3 mg/kg Q2W until disease progression or unacceptable toxicity. Patients in the Opdivo 3 mg/kg Q2W cohort could cross over to O3:Y1 upon progression. The primary endpoint of CheckMate -032 is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS) and the number of treatment-related adverse events leading to drug discontinuation.
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Complete ESMO 2018 Conference Coverage