First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer☆

Abstract

Background: In this first-in-human phase 1 study (NCT02964013; MK-7684-001), we investigated the safety and efficacy of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in combination with pembrolizumab. Patients and methods: Part A enrolled patients with advanced solid tumors, and part B enrolled patients with nonsmall-cell lung cancer (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg in part A and vibostolimab 200 mg alone or with pembrolizumab 200 mg in part B. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective response rate (ORR) per RECIST v1.1. Results: Part A enrolled 76 patients (monotherapy, 34; combination therapy, 42). No dose-limiting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatmentrelated adverse events (TRAEs); grade 3-4 TRAEs occurred in 9% and 17% of patients, respectively. The most common TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was 0% with monotherapy and 7% with combination therapy. In part B, 39 patients had anti-PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-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 TRAEsethe most common were pruritus (38%) and hypoalbuminemia (31%); confirmed ORR was 26%, with responses occurring in both 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 TRAEsethe most common were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy; confirmed ORR was 3% with monotherapy and 3% with combination therapy. Conclusions: Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.

Update in TIGIT Immune-Checkpoint Role in Cancer

“…Patients with advanced solid tumors who received vibostolimab alone or combined with the anti-PD-1 pembrolizumab in a phase I clinical trial (NCT02964013) showed controllable tolerance across escalating doses and all types of advanced solid tumors assessed. Increased NK cell activation of CD8 + T cells was found to have an anticancer effect in the study ( 180 ).…”

The Landscape of Actionable Genomic Alterations by Next-Generation Sequencing in Tumor Tissue Versus Circulating Tumor DNA in Chinese Patients With Non-Small Cell Lung Cancer

“…Tumor responses (CR, complete remission; PR, partial response; SD, stable disease; and PD, progressive disease) were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) (43)(44)(45)(46). The disease control rate (DCR) was defined as all positive responders (including complete, partial, and stable responders) divided by the total number of response-evaluable patients.…”

Immunotherapy in Lung Cancer: Current Landscape and Future Directions

“…A confirmatory phase III trial is ongoing in this patient population (ClinicalTrials.gov identifier: NCT04294810). Early results from a phase I trial of another anti-TIGIT antibody vibostolimab has shown clinical activity in combination with pembrolizumab in PD-1/PD-L1 naïve and refractory patients with advanced NSCLC ( 61 ). An ongoing phase III trial is comparing combination of vibostolimab plus pembrolizumab with pembrolizumab alone in patients with PD-L1 positive advanced NSCLC (ClinicalTrials.gov identifier: NCT04738487).…”