Belrestotug Program Terminated After Mixed Phase 2 Results in NSCLC

The combination of belrestotug (formerly EOS 448), an anti-TIGIT antibody, with the anti–PD-1 agent dostarlimab-gxly (Jemperli) did not demonstrate a clinically meaningful improvement in progression-free survival (PFS) compared with dostarlimab monotherapy in patients with previously untreated, unresectable, locally advanced or metastatic PD-L1–high non–small cell lung cancer (NSCLC), according to updated interim findings from the phase 2 GALAXIES Lung-201 trial (NCT05565378).¹

While the combination regimen did not achieve a PFS benefit, it continued to show a clinically meaningful improvement in objective response rate (ORR), the trial’s primary end point. Despite this signal, the overall efficacy data did not support continued development.

An interim analysis from the phase 2 GALAXIES H&N-202 trial (NCT06062420), which evaluated the combination in PD-L1–positive head and neck squamous cell carcinoma (HNSCC), showed that ORR trends fell below the threshold of clinical significance when compared with dostarlimab monotherapy.

With this, iTeos Therapeutics and GSK have jointly announced the termination of the belrestotug development program. All clinical trial cohorts including belrestotug will be closed, and enrollment in the phase 3 GALAXIES Lung-301 trial (NCT06472076) has been halted.

“We are truly disappointed by the results from GALAXIES Lung-201,” said Michel Detheux, PhD, president and chief executive officer 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.”

About GALAXIES Lung-201

In the phase 2, randomized, open-label GALAXIES Lung-201 trial, patients with previously untreated, unresectable, locally advanced or metastatic NSCLC were enrolled.² Investigators sought to evaluate efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PDy) of novel immunotherapy combinations, including regimens with belrestotug, compared with immunotherapy monotherapy in this patient population.

Enrollment was open to patients with a PD-L1 tumor proportion score of at least 50, those who had received no prior systemic therapy for their locally advanced or metastatic NSCLC, and those with measurable disease based on RECIST 1.1, as determined by the investigator. Patients needed to have an ECOG performance status of 0 or 1, adequate baseline organ function, and EGFR and ALK wild-type disease with no actionable driver mutations. In addition, patients were required to be a current or former smoker, and those who had asymptomatic and treated brain metastases were eligible to enroll in the study.³

In the first substudy, substudy 1A, patients were treated with dostarlimab at a dose of 500 mg given every 3 weeks alone (n = 32) or in combination with belrestotug at a dose of either 100 mg (n = 30), 400 mg (n = 32), or 1000 mg (n = 30).² These made up the 4 arms of the study

At a data cutoff of June 7, 2024, the ORRs in the 4 arms were 37.5% (95% CI, 21.1%-56.3%), 63.3% (95% CI, 43.9%-80.1%), 65.6% (95% CI, 46.8%-81.4%), and 76.7% (95% CI, 57.7%-90.1%). In these respective arms, the confirmed ORR rates were 28.1% (95% CI, 13.7%-46.7%), 60.0% (95% CI, 40.6%-77.3%), 59.4% (95% CI, 40.6%-76.3%), and 63.3% (95% CI, 43.9%-80.1%). All responses were partial, the overall median follow-up was 7.3 months, and 65% of patients remain on treatment.

Safety results showed treatment-emergent adverse effects (AEs) to be seen in 91% (grade ≥3, 44%), 97% (grade ≥3, 63%), 97% (grade ≥3, 50%), and 100% (grade ≥3, 53%) of patients in each of the 4 arms, respectively. In these arms, treatment-related AEs were seen in 59% (grade ≥3, 16%), 80% (grade ≥3, 33%), 84% (grade ≥3, 22%), and 97% (grade ≥3, 43%) of patients, respectively.

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://tinyurl.com/4rsyex2m

2. 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

3. Spigel DR, Korbenfeld EP, Hayashi H, et al. Interim analysis of GALAXIES Lung-201: phase II, randomized, open-label platform study of belrestotug plus dostarlimab in patients (pts) with previously untreated locally advanced/metastatic (LA/M) PD-L1 high (TPS >/=50%) non-small cell lung cancer (NSCLC). Ann Oncol. 2024;35(suppl 2):S1242-S1243. doi:10.1016/j.annonc.2024.08.2294