Safety and Efficacy of Quavonlimab, a Novel Anti-CTLA-4 Antibody (MK-1308), in Combination with Pembrolizumab in First-Line Advanced Non-Small Cell Lung Cancer.

ABSTRACT Background Quavonlimab (MK-1308), a novel anti–CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. Patients and methods Dose-escalation phase (DE): patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy (25 mg [cohort 1], 75 mg [cohort 2], or 200 mg [cohort 3]) followed by 4 treatments of the same quavonlimab dose plus pembrolizumab Q3W. Dose-confirmation phase (DC): patients with stage IIIB/IV NSCLC received first-line quavonlimab (25 mg Q3W [arm A], 25 mg Q6W [arm B], 75 mg Q6W [arm C], or 75 mg Q3W [arm E]) plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. ORR was a secondary end point. Efficacy based on PD-L1 expression, TMB, and changes in circulating CD4+/CD8+ cells were exploratory end points. Results Thirty-nine patients were enrolled in DE (n=14 [cohort 1]; n=17 [cohort 2]; n=8 [cohort 3]) and 134 in DC (n=40 [arm A]; n=40 [arm B]; n=40 [arm C]; n=14 [arm E]). Maximum-tolerated dose was not reached. Grade 3–5 treatment-related AEs occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% (95% CI, 24.9-56.7; arm A), 37.5% (95% CI, 22.7–54.2; arm B), 27.5% (95% CI, 14.6–43.9; arm C), and 35.7% (95% CI, 12.8–64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. Conclusions Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.