Iteos Therapeutics (ITOS) Study Update summary

Study design and objectives

• Phase II GALAXIES-Lung-201 is the largest TIGIT antibody study in lung cancer, designed for dose optimization and component assessment in first-line PD-L1 high non-small cell lung cancer patients.

• The study is a randomized, open-label, global trial in PD-L1 ≥50%, previously untreated, unresectable, locally advanced or metastatic NSCLC patients, evaluating belrestotug + dostarlimab versus monotherapy.

• Primary endpoint is investigator-assessed objective response rate (ORR) per RECIST 1.1; secondary endpoints include safety, progression-free survival, overall survival, and duration of response.

• The study supports FDA Project Optimus principles and informs the ongoing phase III GALAXIES-Lung-301 trial.

• A pembrolizumab arm is included for future direct comparison.

Efficacy results

• Belrestotug + dostarlimab achieved unconfirmed ORR of 63.3%-77% and confirmed ORR of about 60%, compared to 37.5%-38% and 28% for dostarlimab monotherapy.

• Tumor reduction was deeper and more consistent in the doublet arms, with clusters of patients achieving >60% reduction.

• Median ctDNA reduction was highest in Dose B (94%) and Dose C (97%) of the combination, compared to 65% for monotherapy.

• Durable stable disease was observed in the monotherapy arm, indicating benefit beyond response rate.

• No complete responses observed; partial responses and stable disease rates favored the combination arms.

Safety and tolerability

• Safety profile of belrestotug plus dostarlimab was broadly consistent with approved IO combinations, with manageable immune-mediated adverse events.

• Most common treatment-related adverse events were skin/subcutaneous tissue disorders (~50%) and endocrine disorders (~25%), mostly low-grade.

• Three treatment-related deaths occurred (pneumonitis, hepatitis, myocarditis), all immune-related and in the combination arms.

• No new grade 5 adverse events or categories observed in expanded cohorts; safety management improvements are being implemented in phase III.

• Higher immune-mediated adverse event rates were seen at the 1,000 mg dose, but events were generally manageable.