Nivolumab Alone or in Combination With Ipilimumab in Patients With Platinum-Pretreated Metastatic Urothelial Carcinoma, Including the Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg Expansion From CheckMate 032

Bristol-Myers Squibb
Study Design: 
Open-label, multicenter, phase 1/2 study
Immunotherapy has become the recommended treatment for patients with previously treated metastatic urothelial cancer. Preclinical and clinical data indicate that the combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) can improve antitumor activity in advanced melanoma, NSCLC, and mRCC.
Primary endpoints were investigator-assessed confirmed ORR by RECIST v1.1 and duration of response. Secondary endpoints included PFS, OS and safety. Exploratory endpoint was ORR by PD-L1 expression status.
CheckMate 032 is a multicenter, phase 1/2 study and not a randomized trial and one cannot compare across studies. The study reproduces previously presented preliminary results. Selected toxicities were higher but do not preclude treatment. A 38% RR is encouraging. Follow up is not mature but long-term outcomes (tail on curve) may be important. PD-L1 positive tumors may benefit the most (58%). It is still uncertain whether PD-L1 is a good predictive biomarker, as it has been problematic. More detailed interrogation of tumors beyond just PD-L1 would be ideal. A phase III trial is needed and ongoing (CheckMate 901; NCT03036098)
35 patients responded for a 38% RR with 6 CR and 29 PR. The overall response rate by the investigator in patients with baseline PD-L1 >1% status was 58.1% and 54.8% by independent review. PFS assessed by the investigator was 4.9 (2.7–6.6) months. Median OS was 15.3 (10.1–27.6) months. ORR was numerically higher in patients with „1% tumor PD-L1 treated with NIVO1IPI3 (58%), and efficacy was observed across PD-L1 expression levels in all treatment arms.