1134P Safety and efficacy of low dose (LD) ipilimumab (Ipi) + pembrolizumab (pem) in checkpoint inhibitor (CPI) naïve patients (pts) with melanoma brain metastases (MBM)

The CPI combination of standard dose (SD) Ipi (3mg/kg) and nivolumab 1mg/kg (N) has dramatically improved outcomes in pts with MBM but is associated with frequent grade (gr) 3/4 adverse events (AEs). In pts without MBM, LD Ipi (at 1mg/kg) + anti-PD1 with N or Pem has demonstrated promising efficacy with reduced toxicity. We hypothesized this approach would have activity in pts with MBM. We conducted a phase II, single arm and site trial (NCT03873818) evaluating LD Ipi + Pem in pts with MBM. Pts received up to 4 cycles of LD Ipi + Pem, followed by Pem only. At least 1 MBM >/= 5mm was required. CPI naïve (Cohort A) and prior PD-1 (Cohort B) were allowed. Primary objective included intracranial (IC) benefit rate (CBR) – complete response (CR) + partial response (PR) + stable disease (SD) ≥ 6 months (mos) by mRECIST 1.1. Secondary objectives were overall (OS) and progression free (PFS) survival. Study was terminated early due to accrual challenges. Here we report the efficacy results of cohort A. A total 19 of a planned 25 (76%) pts were treated in Cohort A. 58% (11) were male, median age was 63 years (23-88), 7 had BRAF V600 mutation. Median number of MBM was 3 (1-20), median diameter of largest MBM 8 mm (5-28). Pts received a median 4 cycles (1-4) of the combination, median total cycles received was 6 (1-35). IC CBR was 58% (32% CR, 11% PR, 16% SD). At a median follow-up of 14.5 mos (0.5-43), median IC PFS was 8.0 mos (95% CI 1.4- not reached) and median OS has not been reached. 11 (58%) pts in cohort A are alive at time of data lock. 25% (4/16) of pts stopped tx due to progression. 7 pts (37%) stopped tx for AEs. 16 pts experienced AEs at least possibly related to tx, most commonly rash (53%), fatigue (42%), and elevated liver enzymes (32%). Gr 3/4 AEs were observed in 6 (32%) pts, including rash (16%), elevated liver enzymes (11%), nausea, pneumonitis, anorexia, and colitis (5% each). LD Ipi/Pem was well tolerated in CPI naïve pts with MBM, with no new or unexpected AEs, and with promising efficacy. The results support a larger study to confirm benefit.