Antitumor activity and safety of MK-1308 (anti-CTLA-4) plus pembrolizumab (pembro) in patients (pts) with non-small cell lung cancer (NSCLC): Updated interim results from a phase I study.

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2558 Background: An ongoing multicenter, open-label, phase 1 study of the anti–CTLA-4 antibody MK-1308 in combination with pembro in advanced solid tumors (NCT03179436) revealed a manageable safety profile and promising efficacy in pts with first-line (1L) advanced NSCLC. Data from a larger sample size and longer follow-up are presented. Methods: In dose escalation (DE), pts with advanced solid tumors received MK-1308 by IV administration at 25, 75, or 200 mg Q3W ×1 cycle then in combination with pembro 200 mg Q3W ×4 cycles followed by pembro monotherapy (up to 35 cycles). In dose confirmation (DC), pts with 1L advanced NSCLC received MK-1308 at 25 or 75 mg—Q3W or Q6W—plus pembro 200 mg Q3W (up to 35 cycles). Safety (all treated pts), efficacy (subset of 1L NSCLC pts), pharmacokinetics (PK, all treated pts), and PD-L1 tumor expression (subset of 1L NSCLC pts) were analyzed. Results: 213 pts were treated (DE, n=39; DC, n=174). All pts were included in the safety analyses (median follow-up, 8 months); 113 pts from DC were included in the efficacy analyses (median follow-up, 8 months). PK showed a dose-dependent increase in MK-1308 exposure. Neither target dose-limiting toxicity (≥10%) nor maximum tolerated dose were reached for MK-1308 plus pembro; however, toxicity increased with increasing MK-1308 dose and shorter dosing intervals. Treatment-related adverse events grade ≥3 occurred at the lowest rates at 25 mg Q3W in DE (0%) and 25 mg Q6W in DC (25%) and at the highest rates at 200 mg Q3W in DE (75%) and 75 mg Q3W in DC (50%). Efficacy was observed at all MK-1308 dose levels and intervals: confirmed ORR per RECIST 1.1 by central review in 1L advanced NSCLC was 39% at 25 mg Q3W, 33% at 25 mg Q6W, 22% at 75 mg Q6W, and 25% at 75 mg Q3W; 6-month PFS and OS rates are 67% and 89% for the 25 mg Q6W arm. There was a 25% ORR in PD-L1–negative 1L advanced NSCLC pts. Conclusions: MK-1308 plus pembro was generally well tolerated with no unexpected toxicity and conferred encouraging antitumor activity in 1L advanced NSCLC pts. Efficacy, safety, and PK data suggest that 25 mg given Q6W is the recommended phase 2 dose for MK-1308 in combination with pembro. Clinical trial information: NCT03179436.