Frontline Belrestotug Plus Dostarlimab Misses PFS End Point in PD-L1–High NSCLC

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Belrestotug (formerly EOS 448) plus dostarlimab-gxly (Jemperli) failed to elicit a clinically meaningful progression-free survival (PFS) improvement vs dostarlimab monotherapy in patients with previously untreated, unresectable, locally advanced or metastatic, PD-L1–high non–small c/ell lung cancer (NSCLC), according to topline findings from an updated interim analysis of the phase 2 GALAXIES Lung-201 trial (NCT05565378).1

Notably, in this analysis, the combination continued to generate clinically meaningful improvements in objective response rate (ORR)—the trial’s primary end point. Furthermore, an interim analysis of the phase 2 GALAXIES H&N-202 trial (NCT06062420) showed a trend below the meaningful threshold for ORR with belrestotug plus dostarlimab vs dostarlimab monotherapy in patients with PD-L1–positive HNSCC.

However, based on currently available data, iTeos Therapeutics and GSK plan to terminate the belrestotug development program. All belrestotug-containing clinical trial cohorts will end, and enrollment to the phase 3 GALAXIES Lung-301 trial (NCT06472076) has ceased. GSK plans to communicate with institutional review boards, investigators, health authorities, and ethics committees about next steps regarding the appropriate treatment of patients who are currently enrolled in belrestotug trials.

“We are truly disappointed by the results from GALAXIES Lung-201,” Michel Detheux, PhD, president and chief executive officer of iTeos, stated in a news 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.”

GALAXIES Lung-201 enrolled patients with previously untreated, unresectable, locally advanced or metastatic NSCLC who had a PD-L1 tumor proportion score of at least 50%.2 Patients needed to have EGFR and ALK wild-type disease with no actionable driver mutations, and patients were also required to be a current or former smoker. Patients with asymptomatic and treated brain metastases were eligible to enroll.

In substudy 1, patients were randomly assigned to receive dostarlimab at 500 mg every 3 weeks alone (n = 32) or in combination with belrestotug at 100 mg (n = 30), 400 mg (n = 32), or 1000 mg (n = 30). At a data cutoff of June 7, 2024, and an overall median follow-up of 7.3 months, the ORRs in these respective 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%). The respective 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.

Furthermore, belrestotug plus dostarlimab was associated with a greater reduction in tumor size and a greater depth of response vs dostarlimab alone. Investigators also observed a trend toward a numerically greater magnitude of circulating tumor DNA (ctDNA) level decreases that was associated with the dose of belrestotug. Among evaluable patients who received dostarlimab alone (n = 19), belrestotug at 100 mg (n = 18), belrestotug at 400 mg (n = 22), and belrestotug at 1000 mg (n = 20), the median rate of ctDNA change at week 7 was –65%, –55%, –94%, and –97%, respectively.

Regarding safety, treatment-emergent adverse effects (AEs) were reported in 91% (grade ≥3, 44%), 97% (grade ≥3, 63%), 97% (grade ≥3, 50%), and 100% (grade ≥3, 53%) of patients, respectively. Treatment-related AEs were reported 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 13, 2025. https://investors.iteostherapeutics.com/news-releases/news-release-details/iteos-reports-topline-interim-results-galaxies-lung-201-study
2. 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