Safety and efficacy of ipilimumab with or without prophylactic budesonide in treatment-naive and previously treated patients with advanced melanoma

9010 Background: Ipilimumab (ipi), an anti cytotoxic T-lymphocyte antigen-4 monoclonal antibody, has shown activity in small, phase I/II melanoma trials. The purpose of this study was to explore whether prophylactic budesonide (PB) would decrease the rate of diarrhea, a frequent immune-related adverse event (irAE), and assess clinical responses to the regimen. Methods: Patients (pts) with unresectable stage III or stage IV melanoma received ipi 10 mg/kg every 3 weeks (Q3W)×4 induction dosing in combination with placebo (Group A) or PB, an oral steroid with minimal systemic exposure used to treat inflammatory bowel disease (Group B; QD at 9 mg to Week 12, 6 mg to Week 14, and 3 mg to Week 16) in this randomized, double-blind, multicenter, phase II study. Pts were either treatment-naive or treated with prior systemic therapy for advanced melanoma. Eligible pts could enter maintenance treatment with ipi 10 mg/kg Q12W at Week 24. Response was assessed by an Independent Review Committee (IRC) using mWHO criteria. Follow-up tumor evaluation beyond progressive disease (PD) and before the administration of non-ipi anticancer therapy was permitted as per protocol. Results: 115 pts were treated. The rates 95% CI of Grade 2+ diarrhea (regardless of causality) during the initial trial period were 35.1% 22.9 - 48.9 and 32.8% 21.0 - 46.3 for Groups A and B, respectively. Ipi was generally well tolerated; most pts had at least 1 irAE. There were no bowel perforations observed. There was no clinically meaningful difference in the best overall response rate (BORR), disease control rate (DCR), or safety events. BORRs were 15.8% and 12.1% in Groups A and B, respectively. Conclusions: Ipi is well tolerated and efficacious in pts with advanced melanoma. While therapeutic budesonide has activity in the management of low-grade gastrointestinal ipi-related irAEs, PB in advanced melanoma did not meaningfully impact the benefit to risk profile, and is not recommended. Group A (ipilimumab + placebo) Group B (ipilimumab + prophylactic budesonide) BORR (CR + PR) - % 95% CI CR - n (%) 15.8 7.5–27.9 0 (0) 12.1 5.0 - 23.3 1 (1.7) DCR (CR + PR + SD) - % 95% CI 35.1 22.9- 48.9 31.0 19.5 - 44.5 Any irAE - % 84.2 81.0 Grade 3/4 irAE - % Any Gastrointestinal Hepatobiliary Endocrine Skin 38.6 22.8 8.8 5.3 0 41.4 24.1 6.9 5.2 5.2 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Medarex Medarex