Efficacy and safety of ipilimumab induction and maintenance dosing in patients with advanced melanoma who progressed on one or more prior therapies

9021 Background: Ipilimumab (ipi) is a monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4. The current study was designed to determine the efficacy and safety of ipi in patients (pts) with advanced melanoma who developed progressive disease (PD) on prior therapies. Methods: Advanced melanoma pts with PD during or after >1 prior therapeutic regimen were eligible for enrollment into this single-arm, multicenter, phase II study. Ipi induction was given at 10 mg/kg every 3 weeks (Q3W)×4; eligible pts received maintenance Q12W starting at Week (Wk) 24. The primary objective was to evaluate the best overall response rate (BORR, complete + partial response [CR+PR]). Efficacy endpoints were assessed with modified World Health Organization (mWHO) criteria; the first assessment was at Wk 12. Follow-up tumor evaluation beyond PD (defined by an overall tumor burden increase of >25%) by mWHO and before the administration of non-ipi anticancer therapy was permitted as per protocol. Results: The study included 155 treated pts. The median number of prior therapies was 2. The BORR as per an Independent Review Committee (IRC) was 5.8% (9/155) [95% CI, 2.7 - 10.7]. The disease control rate (DCR, best response of CR + PR + stable disease [SD]) was 27.1% (42/155) [95% CI, 20.3 - 34.8]. New exploratory response criteria revealed a >25% reduction of measurable total tumor burden in 25.8% of patients. The progression free survival rate at Wk 24 was 49.1% [95% CI 41.2, 57.9]. Immune-related adverse events (irAEs) occurred in 70.3% of pts. Most patients (46.5%) had Grade 1/2 irAEs. The rates of patients with Grade 3/4 irAEs were: gastrointestinal 8.4%; hepatobiliary 7.1%; endocrine 1.3%; and skin 3.2%. Most irAEs were medically manageable. There were no bowel perforations. Conclusions: Ipi 10 mg/kg induction/maintenance dosing is effective and well tolerated in pts with PD on prior therapies. Clinical activity, in the form of either objective response or SD occurred in 27% of patients. Based on preliminary results from previous studies (eg, MDX010–15), we expect pts with a BOR of SD or better to remain progression free for months to years. Follow up of these pts is ongoing; survival data will be presented at the meeting.