CHECKMATE 214 trial success for Opdivo + Yervoy (low dose) v. sunitinib for renal cell carcinoma.

Bristol-Myers Squibb Company announced patient-reported outcomes data from the Phase III CheckMate -214 trial in intermediate- and poor-risk patients with advanced renal cell carcinoma (RCC) treated with the Immuno-Oncology combination Opdivo (nivolumab) plus low-dose (1mg/kg) Yervoy (ipilimumab) versus sunitinib over a two-year follow-up period. Patients in the study treated with Opdivo plus low-dose Yervoy reported significant benefits in disease-related symptoms and improvements to their cancer-related quality of life and well-being. These benefits occurred early during Opdivo plus low-dose (1mg/kg) Yervoy combination therapy and were largely maintained throughout the treatment period and through Opdivo maintenance therapy.

Relative to the current standard of care, patients in the Opdivo plus low-dose Yervoy arm reported fewer kidney cancer symptoms as measured by the NCCN Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19). This benefit was significant at all but one post-baseline time point through two years of follow-up (P<0.05). Time to deterioration (TTD) in FKSI-19 total score was also significantly delayed with Opdivo plus low-dose Yervoy versus sunitinib (HR 0.54; 95% CI, 0.46–0.63; P < 0.0001). An additional analysis showed similar results with a significant benefit seen for Opdivo plus low-dose Yervoy relative to sunitinib on change from baseline at a pre-planned 25-week landmark. Assessed by FKSI-19 total score, with a mean difference of 3.55 (1.65 vs -1.9; P<0.0001), the analysis showed that patients in the Opdivo plus low-dose Yervoy arm experienced significantly better health-related quality of life scores in regard to disease-related symptoms, treatment side effects and functioning.

Additionally, longitudinal changes from baseline in health-related quality of life between treatment arms at 25 weeks, as assessed by the Functional Assessment of Cancer Therapy-General (FACT-G), also demonstrated a significant advantage for Opdivo plus low-dose Yervoy, with a mean difference of 3.71 (1.52 vs -2.19; P<0.0009) in the total score between arms. Confirmatory results from FACT-G also showed significantly higher scores in the combination arm across a number of measures, including physical, functional and emotional well-being.

Collectively, these data suggest a significant and consistent patient reported benefit of the combination relative to standard of care. Findings will be presented during the Developmental Therapeutics—Immunotherapy poster session on Monday, June 4 from 8:00-11:30 AM CDT at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018 in Chicago (Abstract #3073).

About CheckMate -214 : CheckMate -214 is a Phase III, randomized, open-label study evaluating the combination of Opdivo plus Yervoy versus sunitinib in patients with previously untreated advanced RCC. In the intermediate- and poor-risk study population, 425 patients received Opdivo 3 mg/kg plus Yervoy 1 mg/kg every three weeks for four doses, followed by Opdivo 3 mg/kg every two weeks, and 422 patients received sunitinib 50 mg once daily for four weeks, followed by two weeks off every cycle. The recommended dosing for the Opdivo plus Yervoy combination is Opdivo 3 mg/kg followed by Yervoy 1 mg/kg each infused intravenously over 30 minutes on the same day every three weeks for four doses. After completing four doses of the combination, Opdivo should be administered intravenously 240 mg every two weeks or 480 mg every four weeks over 30 minutes until disease progression or unacceptable toxicity.

The primary efficacy outcome measures of the trial were OS, ORR (CR+PR) and PFS as determined by an independent radiographic review committee (IRRC) in intermediate- and poor-risk patients. Patients were included regardless of their PD-L1 status. Data from CheckMate -214 were previously presented at the European Society for Medical Oncology Congress in September 2017 and the Society for Immunotherapy of Cancer Annual Meeting in November 2017 and were published in the New England Journal of Medicine in March 2018.