GSK and iTeos Achieve Phase II Success for Jemperli-TIGIT Combo in NSCLC

High response rates reported by GSK and iTeos at the 2024 European Society for Medical Oncology Congress offer a ray of light for anti-TIGIT therapies after a string of failures.

GSK and iTeos Therapeutics disclosed data from the Phase II GALAXIES Lung-201 platform Phase II study, revealing that Jemperli, coupled with the experimental anti-TIGIT therapy belrestotug, induced promising response rates in patients with non-small cell lung cancer. After a follow-up period of at least 5.6 months, the combined treatment achieved a verified objective response rate of approximately 60% across all dosages. In a news release, the partners described this outcome as a “clinically meaningful improvement,” highlighting an approximately 30% increase compared to Jemperli (dostarlimab) alone.

The study also demonstrated significant reductions in circulating tumor DNA levels, which fell by 94% and 97% from baseline to week 7 in patients administered 400 mg and 1,000 mg doses of belrestotug, respectively. In contrast, patients receiving only Jemperli experienced a 65% reduction in circulating tumor DNA during the same period.

These findings were presented at the 2024 European Society for Medical Oncology Congress (ESMO 2024). According to Michel Detheux, iTeos’ president and CEO, the partners are “encouraged” by these results, which indicate the “potential differentiation” of combining an anti-TIGIT therapy with a PD-1 treatment. Detheux further stated that the enhanced depth of response in tumor measurement in patients treated with the combination therapy, compared to those treated with PD-1 alone, suggests promising therapeutic potential for a patient population with limited options.

The GALAXIES Lung-201 study is a randomized, open-label trial that compared the doublet therapy to Jemperli monotherapy in non-small cell lung cancer patients with high PD-L1 expression levels. To qualify for the study, patients needed to be previously untreated and have unresectable, locally advanced, or metastatic disease.

Besides efficacy, the study also examined the safety profile of Jemperli plus belrestotug. Results indicated that the combined treatment led to higher rates of immune-related adverse events, which were “generally manageable.” Common treatment-related toxicities included skin and subcutaneous disorders, and endocrine disorders.

GSK and iTeos are advancing the combination regimen toward registration with the newly initiated GALAXIES Lung-301 study, which will concentrate on the same treatment setting and indication. Belrestotug is an IgG1 monoclonal antibody designed to target TIGIT, a crucial inhibitory receptor that cancer cells use to suppress the body's immune responses. By inhibiting TIGIT, belrestotug enhances the body's anti-tumor response, aiding the release of cytokines and activating antibody-dependent cell-killing mechanisms.

With the ESMO 2024 presentation, belrestotug brings renewed optimism to the TIGIT field, which has faced setbacks recently. In May 2024, Merck terminated its Phase III melanoma program after the anti-TIGIT antibody vibostolimab, when combined with Keytruda (pembrolizumab), resulted in high dropout rates due to side effects. In July, Roche also had to discontinue a Phase II/III study after its anti-TIGIT therapy tiragolumab, combined with Tecentriq (atezolizumab), failed to improve progression-free survival in non-squamous NSCLC patients compared to Keytruda plus chemotherapy. In August 2024, BMS withdrew from a $1.5 billion agreement with Agenus and returned the rights to the anti-TIGIT bispecific antibody AGEN1777.