Background: Within this first-in-human phase 1 study (NCT02964013 MK-7684-001), we investigated the security and effectiveness from the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in conjunction with pembrolizumab.

Patients and techniques: Medicare Part A enrolled patients with advanced solid tumors, and medicare part b enrolled patients with non-small-cell cancer of the lung (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg partly A and vibostolimab 200 mg alone or with pembrolizumab 200 mg partly B. Primary endpoints were safety and tolerability. Secondary endpoints incorporated pharmacokinetics and objective response rate (ORR) per RECIST v1.1.

Results: Medicare Part A enrolled 76 patients (monotherapy, 34 combination therapy, 42). No dose-restricting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatment-related adverse occasions (TRAEs) grade 3-4 TRAEs happened in 9% and 17% of patients, correspondingly. The most typical TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was % with monotherapy and sevenPercent with combination therapy. Partly B, 39 patients had anti-PD-1 (programmed cell dying protein 1)/PD-L1 (programmed dying-ligand 1)-naive NSCLC (all received combination therapy), and 67 had anti-PD-1/PD-L1-refractory NSCLC (monotherapy, 34 combination therapy, 33). In patients with anti-PD-1/PD-L1-naive NSCLC: 85% had TRAEs-the most typical were pruritus (38%) and hypoalbuminemia (31%) confirmed ORR was 26%, with responses occurring both in PD-L1-positive and PD-L1-negative tumors. In patients with anti-PD-1/PD-L1-refractory NSCLC: 56% receiving monotherapy and 70% receiving combination therapy had TRAEs-the most typical were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy confirmed ORR was 3% with monotherapy and threePercent with combination therapy.

Conclusions: Vibostolimab plus pembrolizumab was well tolerated and shown antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.