iTeos-GSK TIGIT combo yields 30% greater tumor shrinkage than Jemperli in phase 2

iTeos and GSK are progressing their collaborative efforts, unveiling promising results from their phase 2 TIGIT trial, which has transitioned into the phase 3 GALAXIES Lung-301 trial. The midstage findings, revealed during the European Society for Medical Oncology conference in Barcelona, show a significant improvement in overall response rates for the combination treatment compared to monotherapy.

The phase 2 trial, GALAXIES Lung-201, included patients with untreated, advanced, or metastatic PD-L1-high non-small cell lung cancer (NSCLC). At the June 7 data cutoff, 124 patients were eligible for evaluation, divided into four cohorts. One cohort did not receive TIGIT treatment, while groups A, B, and C received belrestotug at varying doses (100 mg, 400 mg, and 1,000 mg, respectively), alongside 500 mg of dostarlimab for all patients.

The trial's primary endpoint was overall response rate (ORR), showing a meaningful improvement across all TIGIT cohorts. Group A reported a 63.3% ORR, group B had 65.6%, and group C showed 76.7%, compared to 37.5% for the dostarlimab-only group. The median follow-up time varied slightly among groups, with the monotherapy at seven months, groups A and B at 8.5 months, and group C at 6.7 months.

Additionally, the confirmed overall response rate (cORR)—a measure of complete or partial response confirmed by repeat imaging after at least four weeks—was about 60% across all TIGIT doses, against 28.1% for monotherapy. These results highlight a significant 30% difference in response rates between the combination therapy and dostarlimab alone.

Michel Detheux, Ph.D., President and CEO of iTeos, emphasized the potential therapeutic benefits, stating that the depth of tumor response in patients treated with the combination therapy was promising. He confirmed the commitment to leveraging scientific advancements to impact cancer treatment, with a focus on progression-free survival data expected in 2025.

Safety data illustrated a higher incidence of manageable immune-related adverse events with the combination therapy versus monotherapy. The most common treatment-related adverse events were skin and subcutaneous tissue disorders. The safety profile of the combination therapy was consistent with known profiles of checkpoint inhibitor combination therapies.

In May, iTeos and GSK announced that promising interim analysis results had prompted the launch of the phase 3 GALAXIES Lung-301 trial. The phase 3 trial began in July, aiming to enroll around 1,000 patients. It will compare the belrestotug-Jemperli combination against a placebo-Keytruda arm, with a primary completion date expected in 2028.

Despite Roche’s setbacks with its TIGIT tiragolumab in late-stage trials, iTeos and GSK remain optimistic about their development path. The companies had to reassess their strategies after a phase 3 Roche flop but continue to push forward, with belrestotug currently under investigation in six separate clinical trials.

GSK’s initial investment in the co-development and co-commercialization of belrestotug included a $625 million upfront payment to iTeos, with potential milestones totaling up to $1.45 billion. While Roche’s challenges have caused some reconsideration in the field, iTeos and GSK are committed to advancing their investigational therapy, aiming to offer new hope for patients with limited treatment options.