8-K: iTeos Therapeutics Announces Positive Interim Results for Belrestotug Combination Therapy in Lung Cancer

iTeos Therapeutics reported clinically meaningful objective response rates in a Phase 2 trial for its belrestotug and dostarlimab combination therapy for non-small cell lung cancer.

Summary

• iTeos Therapeutics announced interim data from the GALAXIES Lung-201 Phase 2 study, evaluating belrestotug in combination with dostarlimab for previously untreated, advanced non-small cell lung cancer with high PD-L1 expression.
• The study showed a clinically meaningful objective response rate (ORR) ranging from 63.3% to 76.7% across different doses of belrestotug combined with dostarlimab.
• The confirmed ORR (cORR) was approximately 60% for each dose of the combination therapy, compared to 28.1% for dostarlimab alone.
• There was a greater than 30% difference in cORR between the belrestotug and dostarlimab combination and dostarlimab monotherapy.
• The combination therapy also showed a numerically greater reduction in circulating tumor DNA (ctDNA) compared to dostarlimab alone, particularly at the 400mg and 1000mg doses of belrestotug.
• The safety profile of the combination was broadly consistent with known safety profiles of checkpoint inhibitor combinations, with manageable immune-related adverse events.
• The company has initiated a Phase 3 registration study, GALAXIES Lung-301, in the same indication and setting.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results with a significant improvement in response rates and manageable safety, suggesting a strong potential for the drug combination. The initiation of a Phase 3 trial further boosts the positive outlook.

Positives

• The combination therapy demonstrated a significant improvement in ORR compared to dostarlimab alone.
• The consistent cORR across different doses of belrestotug suggests a robust treatment effect.
• The numerically greater reduction in ctDNA indicates a deeper response to the combination therapy.
• The safety profile was manageable and consistent with other checkpoint inhibitor combinations.
• The initiation of the Phase 3 trial, GALAXIES Lung-301, indicates confidence in the therapy's potential.

Negatives

• The combination therapy led to an increase in immune-related adverse events compared to dostarlimab monotherapy.
• Some patients experienced serious treatment-related adverse events, including fatal cases of immune-mediated pneumonitis, hepatitis, and myocarditis.
• Treatment-related adverse events led to discontinuation of therapy in some patients.

Risks

• The success of the Phase 2 trial does not guarantee success in the Phase 3 trial.
• Interim data may change as more patient data becomes available.
• The company may face challenges in manufacturing and regulatory approvals.
• Negative developments in the field of immuno-oncology could impact the therapy's success.
• The company's financial resources may be limited.

Future Outlook

The company plans to present longer-term follow-up data from the GALAXIES Lung-201 study in 2025 and is currently enrolling patients in the Phase 3 GALAXIES Lung-301 trial. They also expect to have data from the Phase 2 TIG-006 and GALAXIES H&N-202 trials in 2025.

Management Comments

• Michel Detheux, Ph.D., president and chief executive officer of iTeos, stated that the data underscores the potential differentiation of their TIGIT:PD-1 doublet.
• Brian Henick, M.D., from Columbia University Irving Medical Center, noted the medical community's need for new treatment options and the promising progress of the belrestotug + dostarlimab doublet.

Industry Context

This announcement is significant in the immuno-oncology space, as it highlights the potential of TIGIT inhibitors in combination with PD-1 inhibitors for treating non-small cell lung cancer. The results suggest a potential improvement over existing checkpoint inhibitor monotherapies, which are a standard of care for this disease.

Comparison to Industry Standards

• The confirmed ORR of approximately 60% for the belrestotug + dostarlimab combination is notably higher than the 28.1% observed with dostarlimab monotherapy in this study, and also appears to be higher than historical results for PD-1 monotherapy in similar patient populations.
• While direct comparisons are difficult without head-to-head trials, the results suggest a potential advantage over other TIGIT inhibitors in development, such as Merck's vibostolimab and Arcus' domvanalimab, particularly given the observed Treg depletion with belrestotug.
• The study's results are also being compared to other checkpoint inhibitor combinations, such as pembrolizumab plus chemotherapy, which have shown efficacy in first-line NSCLC, but the belrestotug combination may offer a chemotherapy-free option.
• The ongoing Phase 3 trial, GALAXIES Lung-301, will provide a more definitive comparison to the current standard of care, which often includes pembrolizumab.

Stakeholder Impact

• Shareholders are likely to react positively to the strong clinical data and the initiation of the Phase 3 trial.
• Patients with advanced non-small cell lung cancer may benefit from this new treatment option.
• The company's employees may be motivated by the positive results and the potential for commercial success.
• The company's development partner, GSK, will likely be encouraged by the data and continue to support the program.

Next Steps

• The company will present longer-term follow-up data from the GALAXIES Lung-201 study in 2025.
• The company is currently enrolling patients in the Phase 3 GALAXIES Lung-301 trial.
• The company expects to have data from the Phase 2 TIG-006 and GALAXIES H&N-202 trials in 2025.

Key Dates

Keywords

belrestotug, dostarlimab, non-small cell lung cancer, NSCLC, TIGIT, PD-L1, immuno-oncology, objective response rate, ORR, clinical trial, GALAXIES Lung-201, GALAXIES Lung-301, ctDNA