iTeos and GSK Launch Phase 3 Study of Belrestotug and Dostarlimab in PD-L1 Non-Small Cell Lung Cancer

On June 17, 2024, iTeos Therapeutics, Inc. (Nasdaq: ITOS) and GSK announced the commencement of a pivotal Phase 3 clinical trial for their innovative immuno-oncology treatment combining belrestotug and dostarlimab. This global study will evaluate the efficacy of this combination therapy versus a placebo paired with pembrolizumab in patients with previously untreated, unresectable, locally advanced or metastatic PD-L1 selected non-small cell lung cancer (NSCLC).

iTeos Therapeutics, a biopharmaceutical company headquartered in Watertown, MA, USA, with a research center in Gosselies, Belgium, focuses on developing next-generation immuno-oncology treatments. The company's president and CEO, Michel Detheux, Ph.D., expressed optimism about this new phase in their oncology endeavors. He highlighted the significance of the Phase 3 trial, noting that nearly 70% of patients with first-line PD-L1 high NSCLC benefit from chemotherapy-free treatments. Detheux emphasized that the belrestotug and dostarlimab combination has the potential to enhance therapeutic regimens for these patients and set new standards in cancer care.

The trial, known as GALAXIES Lung-301, is a randomized, double-blind, placebo-controlled, multicenter study. It aims to enroll around 1,000 patients from North America, South America, Europe, and Asia. Participants will be randomly assigned in a 1:1 ratio to receive either the belrestotug and dostarlimab combination or a placebo with pembrolizumab. The primary objectives of the study are to measure progression-free survival and overall survival.

This Phase 3 trial follows promising results from the Phase 2 GALAXIES Lung-201 study. In May 2024, iTeos announced that the interim assessment of this earlier trial had exceeded predefined efficacy criteria for clinically relevant activity. The belrestotug and dostarlimab combination demonstrated an acceptable safety profile consistent with the TIGIT:PD-1 class and showed meaningful tumor reduction across all dosages compared to dostarlimab monotherapy.

Belrestotug, also known as EOS-448 or GSK4428859A, is a human immunoglobulin G1 (IgG1) monoclonal antibody that targets TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains). This receptor plays a significant role in suppressing innate immune responses against cancer. As an optimized, high-affinity anti-TIGIT monoclonal antibody, belrestotug is designed to boost antitumor responses through a multifaceted immune modulatory mechanism. It engages with TIGIT and FcγR, a crucial immune response regulator, inducing cytokine release and antibody-dependent cellular cytotoxicity (ADCC). This therapeutic candidate is being developed for multiple indications in partnership with GSK.

iTeos Therapeutics leverages deep insights into tumor immunology and immunosuppressive pathways to create novel treatments aimed at restoring the immune system's ability to combat cancer. Their pipeline includes three clinical-stage programs targeting novel, validated immunosuppressive pathways with optimized pharmacologic properties for improved clinical outcomes. These include the TIGIT/CD226 axis and the adenosine pathway.

The initiation of the Phase 3 trial marks a critical step for iTeos and GSK in their ongoing efforts to advance cancer treatment. By exploring the potential of belrestotug and dostarlimab to improve outcomes for patients with PD-L1 selected NSCLC, they aim to pave the way for new standards in oncology therapeutics.