Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets).
Georgina V. Long, Victoria Atkinson, Serigne Lo, Alexander Guminski, Shahneen Sandhu, Michael P. Brown, Maria Gonzalez, Richard A. Scolyer, Louise Emmett, Grant A. McArthur, Alexander M. Menzies
Abstract
9508 Background: Preliminary data from the ABC (76 pts) and CheckMate 204 (94 pts) trials showed that nivo and nivo+ipi have activity in active melanoma brain metastases, with durable responses in a subset of pts. Here, we report updated 5-yr data from all pts enrolled on the ABC trial (NCT02374242). Methods: This open-label ph2 trial enrolled 3 cohorts of pts with active melanoma brain mets naïve to anti-PD1/PDL1/PDL2/CTLA4 from Nov 2014-Apr 2017. Pts with asymptomatic brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3Wx4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets i) that failed local therapy, ii) with neuro symptoms and/or iii) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed. The primary endpoint was best intracranial response (ICR) ≥wk12. Key secondary endpoints were IC PFS, overall PFS, OS, & safety. Results: A total of 76 pts (med f/u 54 mo) were enrolled; median age 59y, 78% male. For cohorts A, B and C: elevated LDH 51%, 58% and 19%; V600BRAF 54%, 56% and 81%; prior BRAFi 23%, 24%, 75%. Efficacy and toxicity are shown in the table. There were no treatment-related deaths. 1/17 deaths in cohort A & 4/16 in cohort B were due to IC progression only. Conclusions: Nivo monotherapy and ipi+nivo are active in melanoma brain mets, with durable responses in the majority of patients who received ipi+nivo upfront. A study of upfront ipi+nivo+/-SRS is underway (NCT03340129). Clinical trial information: NCT02374242. [Table: see text]