2023 World Conference on Lung Cancer (Posters)-P2.06. Study Design to Assess Anti-TIGIT Mab Combination with Dostarlimab vs Pembrolizumab or Dostarlimab Monotherapy in NSCLC

P2.06. Study Design to Assess Anti-TIGIT Mab Combination with Dostarlimab vs Pembrolizumab or Dostarlimab Monotherapy in NSCLC - PDF(Abstract)

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This document provides an overview of a study design for assessing the combination of anti-TIGIT Mab with dostarlimab compared to pembrolizumab or dostarlimab monotherapy in non-small cell lung cancer (NSCLC). The study aims to evaluate the efficacy, safety, and pharmacokinetics of different doses of GSK4428859A, an antibody that inhibits TIGIT, when combined with the anti-PD-1 antibody dostarlimab.<br /><br />The introduction section discusses the role of immune checkpoint blockade in NSCLC and the need for new approaches due to varying patient responses and resistance. The CD226 axis, involving the receptor CD226 and the checkpoints TIGIT, CD96, and PVRIG, has emerged as a critical regulator of anticancer response. TIGIT expression is upregulated in activated CD8 T cells, and its higher binding affinity for CD155 can suppress T-cell and NK cell function. Data suggest that TIGIT could act as a checkpoint inhibitor for tumor-infiltrating lymphocytes, and dual blockade of TIGIT and PD-1 may enhance therapeutic activity. Phase 2 trials have shown improved outcomes with TIGIT inhibition in NSCLC patients with high PD-L1 expression.<br /><br />The methods section describes the ongoing open-label, randomized, phase 2 study. Patients with previously untreated, locally advanced/metastatic NSCLC and high PD-L1 expression are eligible for enrollment. The primary endpoint is the objective response rate at 6 months minimum follow-up. Secondary endpoints include progression-free survival, overall survival, duration of response, safety measures, and pharmacokinetics.<br /><br />In summary, this study aims to assess the combination of anti-TIGIT Mab with dostarlimab in NSCLC. The rationale is based on the potential of TIGIT inhibition to enhance the anticancer response when combined with PD-1 inhibition. The study design and endpoints will evaluate the efficacy, safety, and pharmacokinetics of this combination therapy. Enrollment for the study began in October 2022 and is ongoing.

Asset Subtitle

Byoung Chul Cho

Meta Tag

Speaker Byoung Chul Cho

Topic Metastatic NSCLC: Immunotherapy - Prospective

Keywords

anti-TIGIT Mab

dostarlimab

pembrolizumab

dostarlimab monotherapy

non-small cell lung cancer

NSCLC

GSK4428859A

immune checkpoint blockade

CD226 axis

TIGIT inhibition