Small biotechnology company iTeos Therapeutics could succeed where larger drugmakers have fallen short, should study results it presented Saturday at a cancer research conference hold up in further testing.The results, from a mid-stage clinical trial, show that adding iTeos drug to an approved GSK immunotherapy shrank lung tumors in roughly twice as many people as GSKs therapy alone. They have been anticipated since May, when iTeos said the two-drug regimen surpassed its expectations treating a common form of lung cancer.ITeos may face some questions on the safety of combining the two medicines, which both ramp up the bodys immune attack on tumors. Three patients in the trial died from immune-related inflammation that study investigators judged as related to treatment. All three were in study arms involving ITeos drug; none of the 32 trial participants given only GSKs therapy, Jemperli, died from treatment-related side effects.This kind of inflammatory reaction is a known risk of medicines like Jemperli and has resulted in deaths in other immunotherapy studies. ITeos, in an email to BioPharma Dive, said that it expects the safety profile of its regimen to be in line with existing immunotherapy combinations.ITeos drug has drawn attention in large part due to the protein that it targets. Called TIGIT, the protein is thought to stifle the immune response to cancer, suggesting that blocking it could supercharge the anti-tumor effects of Jemperli and other similar immunotherapies.Pharmaceutical companies, among them Roche, Merck & Co., Gilead Sciences and Bristol Myers Squibb, have spent years chasing that hypothesis, with little to show for their efforts. Several important studies failed to show blocking TIGIT helps, sparking doubts about the target that led some companies to pull back on further research.While early, iTeos' data could rekindle some of that interest. The tumor responses it presented Saturday at the European Society for Medical Oncology's annual meeting in Barcelona generally meet the bar Wall Street analysts had set for success.In the trial, which enrolled 124 people with untreated advanced or metastatic non-small cell lung cancer, iTeos tested three doses of its drug, belrestotug, alongside Jemperli. Another group received Jemperli monotherapy. Initial overall response rates, which assess how much tumors shrink, ranged between 63% and 77% across the three combination arms, compared to 38% for Jemperli alone.ITeos repeated tumor imaging scans four weeks or later following those initial responses. On this confirmed basis, overall response rates were roughly 60% in each of the combination groups, versus 28% for Jemperli.This is why were so excited to come to Barcelona, said Michel Detheux, iTeos president and CEO. We are really reaching a stage where we can confirm our best-in-class strategy.In notes to clients ahead of ESMO, analysts at Piper Sandler and Leerink Partners sketched out slightly different scenarios by which iTeos could claim a positive outcome. Christopher Raymond, at Piper Sandler, described the data bogey as response rates in the range of 55% to 60%. Leerink PartnersDaina Graybosch set a somewhat higher range, of 60% to 70%.Mercks immunotherapy Keytruda, which is standard treatment for the group of lung cancer patients iTeos enrolled in its trial, is associated with overall response rates of around 40%. Both analysts thought iTeos would need to show response rates between 20 to 30 percentage points higher than that.All of the responses recorded by iTeos were considered partial, meaning treatment did not completely eradicate tumors. ITeos also analyzed the amount of DNA shed by tumors and circulating in the blood, and found greater reductions at higher combination doses.Its unclear whether the combination of Iteos and GSKs drugs will prolong survival or slow disease progression compared to Jemperli, both of which are stronger measures of a cancer drugs impact. The study is ongoing, and Iteos intends to report further data in the future.About one-quarter to 37% of the patients in each combination dose group experienced serious side effects related to treatment, compared to 9% in the Jemperli group. Discontinuation rates from these adverse events ranged from 16% to 40% in the combination arms, versus 6% in the control. The three deaths were due to immune-mediated pneumonitis, immune-mediated hepatitis and immune-mediated myocarditis.ITeos data come after negative trials earlier this year for TIGIT drugs from Roche and Merck. In August, Bristol Myers Squibb ended a TIGIT research alliance with Agenus. This has contributed to what Leerinks Graybosch described as TIGIT exhaustion and skepticism.But the most important trial result is still pending. Roches SKYSCRAPER-01 study has been running for years and final survival data are expected this year. Preliminary data that was inadvertently disclosed in 2023suggested a benefit was emerging, but at the time wasnt strong enough to be statistically clear. A prior look had found that adding Roches drug, tiragolumab, to the immunotherapy Tecentriq didnt delay tumor progression over Tecentriq alone in lung cancer patients.With GSK, Iteos has also already begun a Phase 3 test of belrestotug and Jemperli against Keytruda. '
