iTeos Therapeutics and partner GSK have discontinued development of the investigational therapy belrestotug based on updated interim results from the Phase II GALAXIES Lung-201 (NCT05565378) and GALAXIES H&N-202 (NCT06062420) trials.^1-4

Why Did iTeos and GSK Discontinue Belrestotug Development?

In these trials, belrestotug in combination with Jemperli (dostarlimab) doublet fell short of critical efficacy thresholds in patients with previously untreated, unresectable, locally advanced or metastatic PD-L1 high non-small cell lung cancer (NSCLC) and PD-L1-positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), respectively. The decision will halt all ongoing belrestotug trials, including enrollment in the Phase III GALAXIES Lung-301 trial (NCT06472076).⁵

“We are truly disappointed by the results from GALAXIES Lung-201,” said Michel Detheux, PhD, president and CEO of iTeos, in a press release. “Following the analysis of the TIGIT data generated to-date with GSK, we have made the mutual decision to discontinue development of all ongoing TIGIT studies. We are grateful to all patients, caregivers, and investigators involved in the GALAXIES studies and believe it is important to share these data with the scientific community at an upcoming medical meeting in order to advance our collective understanding of immuno-oncology and TIGIT.”¹

Belrestotug is an Fc active human immunoglobulin G1 monoclonal antibody that targets T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT), which inhibit the immune response against cancer. The drug was developed to improve the antitumor response by engaging TIGIT and FcγR, which regulates immune responses that induce cytokine release and antibody-dependent cellular cytotoxicity.¹

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. It has shown potential both as a monotherapy and in combination with standard of care and novel cancer therapies, particularly in patients who have limited treatment options.

In August 2023, the FDA approved Jemperli with carboplatin and paclitaxel, followed by Jemperli as a monotherapy, for the treatment of adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test, or microsatellite instability high based on findings from an interim analysis of the first part of the RUBY/ENGOT-EN6/GOG3031/NSGO trial.⁶ The FDA previously approved Jemperli as a single agent in adults with dMMR recurrent or advanced endometrial cancer that has progressed on or after prior treatment with a platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation.

Trial Design

GALAXIES Lung-201 enrolled patients with previously untreated, unresectable, locally advanced or metastatic NSCLC with a PD-L1 tumor proportion score of at least 50%.

The trial’s primary endpoint was objective response rate (ORR) determined by RECIST v1.1 criteria and investigator assessment. Key secondary endpoints included progression-free survival (PFS), overall survival, duration of response, safety, pharmacokinetics, and antidrug antibodies.

GALAXIES H&N-202 is analyzing the antitumor activity and safety of novel immunotherapy combinations compared with Jemperli in patients with PD-L1-positive recurrent or metastatic HNSCC. The trial’s primary endpoint is to compare confirmed ORR between substudies and Jemperli monotherapy.

Interim results from GALAXIES Lung-201 show the combination continued to produce clinically meaningful improvements in ORR. However, data show the combination did not reach the established criteria for clinically meaningful improvements for PFS compared to Jemperli monotherapy. Meanwhile, interim data from GALAXIES H&N-202 trial show a trend below the meaningful threshold for ORR with belrestotug plus Jemperli compared to Jemperli monotherapy in patients with PD-L1-positive HNSCC.

Based on these data, iTeos and GSK will terminate the belrestotug development program and all belrestotug-containing clinical trial cohorts will stop. GSK stated it will collaborate with institutional review boards, researchers, health authorities, and ethics committees to provide appropriate treatment for patients currently enrolled in these trials.

“Since founding this company over a decade ago, I could not be prouder of the team we have built, the quality of science produced, and our collective commitment to improving the lives of cancer patients in need,” Detheux said in the release. “However, given current market conditions and our appreciation of the responsibility to our valued shareholders, we believe the best path forward is to promptly evaluate a full range of strategic alternatives to unlock the value of our assets. With a strong balance sheet and a commitment to disciplined execution, we are well positioned to pursue opportunities that maximize shareholder value.”¹

References

1. iTeos Reports Topline Interim Results from GALAXIES Lung-201 Study of Belrestotug + Dostarlimab in First-Line, PD-L1 High Non-Small Cell Lung Cancer Patients. News release. iTeos Therapeutics Inc. May 13, 2025. Accessed May 14, 2025. https://www.globenewswire.com/news-release/2025/05/13/3080020/0/en/iTeos-Reports-Topline-Interim-Results-from-GALAXIES-Lung-201-Study-of-Belrestotug-Dostarlimab-in-First-Line-PD-L1-High-Non-Small-Cell-Lung-Cancer-Patients.html

2. GSK provides update on belrestotug development programme. News release. GSK. May 13, 2025. Accessed May 14, 2025. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-belrestotug-development-programme/

3. A Study of Belrestotug Plus Dostarlimab Compared With Placebo Plus Pembrolizumab in Previously Untreated Participants With Programmed Death Ligand 1 (PD-L1) High Non-small-cell Lung Cancer (NSCLC). ClinicalTrials.gov. Updated November 11, 2024. Accessed May 14, 2025. https://clinicaltrials.gov/study/NCT05565378?cond=NCT05565378&rank=1

4. A Platform Study of Novel Immunotherapy Combinations as First-Line Treatment in Participants With PD-L1 Positive Recurrent/​Metastatic Squamous Cell Carcinoma of the Head and Neck- GALAXIES H&N-202. ClinicalTrials.gov. Updated November 26, 2024. Accessed May 14, 2025. https://clinicaltrials.gov/study/NCT06062420

5. A Platform Study of Novel Immunotherapy Combinations in Participants With Previously Untreated, Advanced/​Metastatic Non-Small-Cell Lung Cancer. ClinicalTrials.gov. Updated November 12, 2024. Accessed May 14, 2025. https://clinicaltrials.gov/study/NCT05565378?cond=NCT05565378&rank=1

6. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GlaxoSmithKline. July 31, 2023. Accessed May 14, 2025. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-in-us-for-new-indication/