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 revealed data Saturday from the Phase II GALAXIES Lung-201 platform Phase II study, showing that Jemperli and the investigational anti-TIGIT therapy belrestotug elicited promising response rates in patients with non-small cell lung cancer.
After at least 5.6 months of follow-up, the combination treatment resulted in a confirmed objective response rate of approximately 60% for every dose. In iTeos’ news release of the data drop, the partners called this effect a “clinically meaningful improvement,” noting that it represented an increase of around 30% versus Jemperli (dostarlimab) alone.
Circulating tumor DNA levels also dropped by 94% and 97% from baseline to week 7 in patients who received 400 mg and 1,000 mg of belrestotug, respectively. Jemperli monotherapy counterparts, on the other hand, saw a 65% dip in circulating tumor DNA during this time frame.
GSK and iTeos presented these data at the 2024 European Society for Medical Oncology Congress (ESMO 2024).
Michel Detheux, iTeos’ president and CEO, noted in a statement that the partners are “encouraged” by these data, which points to the “potential differentiation” of combining an anti-TIGIT therapy with a PD-1 treatment.
“The improvement in depth of response in tumor measurement in patients treated with the doublet compared to those treated with PD-1 alone holds promising therapeutic potential for a patient population with limited options,” Detheux added.
GALAXIES Lung-201 is a randomized and open-label study that pit the doublet therapy against Jemperli monotherapy in non-small cell lung cancer patients deemed to have high expression levels of PD-L1. To be eligible for inclusion, patients should have been previously untreated and have unresectable and locally advanced or metastatic disease.
Aside from efficacy, GALAXIES Lung-201 also looked at the safety of Jemperli plus belrestotug. Results showed that the doublet resulted in higher rates of immune-related adverse events, though these were “generally manageable,” according to Saturday’s news release. Common treatment-related toxicities include skin and subcutaneous disorders, and endocrine disorders.
GSK and iTeos are continuing to push the combo regimen toward registration with the recently launched GALAXIES Lung-301 study, which will focus on the same treatment setting and indication.
Belrestotug is an IgG1 monoclonal antibody designed to target TIGIT, a crucial inhibitory receptor that cancer cells exploit to suppress the body’s innate and adoptive immune responses. By blocking TIGIT, belrestotug boosts the body’s anti-tumor response, helping to release cytokines and activate antibody-dependent cell-killing mechanisms.
With the ESMO 2024 readout, belrestotug returns some much-needed enthusiasm in the TIGIT space, which in recent months has hit a rough patch. In May 2024, Merck scrapped its Phase III melanoma program after the anti-TIGIT antibody vibostolimab, when combined with Keytruda (pembrolizumab), elicited high rates of study dropout due to side effects.
In July, Roche was also forced to end a Phase II/III study after its anti-TIGIT therapy tiragolumab, plus Tecentriq (atezolizumab), failed to boost progression-free survival in non-squamous NSCLC patients versus Keytruda plus chemotherapy. A month later, in August 2024, BMS turned its back on a $1.5 billion contract with Agenus and gave back the rights to the anti-TIGIT bispecific antibody AGEN1777.
