iTeos' TIGIT Drug Reduces Lung Tumors in Trial

A small biotechnology company, iTeos Therapeutics, has showcased promising results that could potentially rejuvenate interest in a challenging area of cancer treatment where larger pharmaceutical companies have struggled. iTeos presented data from a mid-stage clinical trial at a recent cancer research conference, revealing that their investigational drug, when combined with an existing GSK immunotherapy, demonstrated a notable reduction in lung tumors. This combination therapy outperformed the GSK immunotherapy alone, doubling the response rate.

The findings have been eagerly awaited since May, when iTeos announced that their two-drug regimen had exceeded expectations in treating a prevalent form of lung cancer. The trial involved 124 participants with advanced or metastatic non-small cell lung cancer who had not received prior treatment. They were divided into groups receiving different doses of iTeos' drug, belrestotug, alongside GSK’s Jemperli, and another group receiving only Jemperli.

The initial overall response rates, which measure tumor shrinkage, ranged from 63% to 77% across the different combination doses, compared to 38% for Jemperli alone. Follow-up imaging confirmed these responses, with approximately 60% response rates in the combination groups versus 28% for Jemperli.

Despite the promising efficacy, there are safety concerns. Three patients in the trial died from treatment-related immune-related inflammation, specifically in the combination therapy groups. No deaths were reported among those receiving only Jemperli. Such inflammatory reactions are known risks with immunotherapies and have been observed in other studies. iTeos anticipates their regimen's safety profile to align with existing immunotherapy combinations.

iTeos’ drug targets a protein called TIGIT, believed to hinder the immune system's ability to attack cancer. Blocking TIGIT is thought to enhance the effects of immunotherapies like Jemperli. While several major pharmaceutical companies, including Roche, Merck, Gilead Sciences, and Bristol Myers Squibb, have explored this hypothesis, many have not succeeded, leading to skepticism about TIGIT as a target.

However, iTeos’ data might reignite interest in TIGIT. The response rates they presented align with what Wall Street analysts expected for success. For instance, analysts from Piper Sandler and Leerink Partners suggested that response rates needed to be significantly higher than those associated with standard treatments, like Merck's Keytruda, which typically shows a 40% response rate in similar patient groups.

All responses recorded in the iTeos trial were partial, meaning the tumors were reduced but not entirely eradicated. Additionally, iTeos evaluated the levels of tumor DNA circulating in the blood and found that higher combination doses led to greater reductions.

The true impact of combining iTeos and GSK’s drugs on survival and disease progression remains uncertain. The study continues, and iTeos plans to release more data in the future. Serious side effects were noted in 25% to 37% of patients in the combination groups, compared to 9% in the Jemperli group. The discontinuation rate due to adverse events was also higher in the combination arms.

These results come on the heels of disappointing trials for other TIGIT-targeting drugs from Roche and Merck earlier this year. Bristol Myers Squibb also ended a TIGIT research collaboration recently, contributing to a general skepticism about TIGIT.

However, the most critical pending trial is Roche's SKYSCRAPER-01, which has been ongoing for years. The final survival data are expected this year, and preliminary results indicated a potential benefit, though not statistically significant at the time. Roche’s previous interim analysis showed that adding their TIGIT-targeting drug, tiragolumab, to Tecentriq did not significantly delay tumor progression compared to Tecentriq alone.

iTeos, along with GSK, has already initiated a Phase 3 trial comparing the combination of belrestotug and Jemperli against Keytruda, seeking to further validate their approach.