Preliminary data from the ABC (76 pts, med f/u 17mo) and CheckMate 204 (94 pts, med f/u 14mo) 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 the survival and updated response data from all pts enrolled (Nov 2014-Apr 2017) on the randomised Ph2 ABC trial (NCT02374242) of 3 cohorts of pts with active melanoma brain mets naïve to anti-PD1/PDL1/CTLA4.
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. Secondary endpoints were best extracranial response (ECR), best overall response, IC PFS, EC PFS, overall PFS, OS, & safety.
76 pts (med f/u 34 mo) were enrolled; median age 59y, 78% male. For cohorts A, B and C: elevated LDH 51%, 58% and 19%; V600 BRAF 54%, 56% and 81%; prior BRAFi 23%, 24%, 75%. The ICR/ECR in A, B and C were 51%/57%, 20%/29% and 6%/25%, respectively, with complete ICR in 26%, 16% and 0%. The 12- and 24-mo IC PFS were cohort A: 49% and 49%, B: 20% and 15% and C: 6% and 6%, and the 12- and 24-mo OS were A: 63% and 63%, B: 60% and 51% and C: 31% and 19%. ICR and 24-mo IC PFS in cohort A drug treatment naïve (n = 27) were 59% and 56%, respectively. Treatment-related AEs gd 3/4 toxicity in A, B and C were 54%, 20% and 13%, respectively. There were no treatment-related deaths. Quality of life was assessed using EQ-5D-5L, QOL C30 and BM-20 questionnaires.
With longer follow up, upfront ipi+nivo demonstrates durable IC responses in the majority of patients, with no new AEs. A study of upfront ipi+nivo+SRS vs ipi+nivo is planned (NCT03340129).
Clinical trial identification
Legal entity responsible for the study
Melanoma Institute Australia.
G.V. Long: Advisory / Consultancy: Aduro, Amgen, BMS, Mass-Array, Merck MSD, Novartis, ONcosec, Pierre Fabre, Roche. V.G. Atkinson: Honoraria (self): BMS, MSD, Merck Serono, Pierre Fabre, Roche, Novartis; Advisory / Consultancy: BMS, MSD, Merck Serono, Pierre Fabre, Roche, Novartis; Speaker Bureau / Expert testimony: BMS, MSD, Merck Serono, Roche, Novartis; Travel / Accommodation / Expenses: BMS, MSD, Roche, Onco-Sec. S.K. Sandhu: Honoraria (self): Janssen, Bristol-Myers Squibb, Roche/Genentech, Merck Sharp and Dohme and Merck Serono; Research grant / Funding (institution): Merck, Merck Serono, Bristol-Myers Squibb, Amgen,Tolmar; Travel / Accommodation / Expenses: Genentech, Janssen, Merck. M. Brown: Honoraria (institution): BMS. A. Guminski: Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Kga, SunPharm; Advisory / Consultancy: Eisai, Regeneron, Sandofi. R.A. Scolyer: Advisory / Consultancy: Merck, Sharp & Dohme, Novartis, Myriad, NeraCare. A.M. Menzies: Advisory / Consultancy: BMS, MSD, Novartis, Roche, Pierre Fabre. G.A. McArthur: Honoraria (institution): - Genentech/Roche - MSD - BMS - Array BioPharm - Amgen - Pfizer. All other authors have declared no conflicts of interest.