Tiragolumab

iTeos and GSK are launching their spaceship into another galaxy, touting phase 2 findings that prompted the late-stage GALAXIES Lung-301 trial. After announcing a phase 3 launch based on positive midstage results, iTeos and GSK are finally sharing the highlights from the phase 2 TIGIT trial, revealing a more than 30% difference in confirmed overall response rates between the investigational treatment versus monotherapy.The interim data cut assesses belrestotug, an anti-TIGIT antibody, plus dostarlimab, GSK’s anti-PD-1 treatment sold under the name Jemperli. Findings were shared in a late-breaking abstract on Sept. 14 at this year’s European Society for Medical Oncology conference in Barcelona.The midstage trial, dubbed GALAXIES Lung-201, evaluated the combo among patients with previously untreated, unresectable, locally advanced or metastatic PD-L1-high non-small cell lung cancer (NSCLC).At the June 7 data cutoff, 124 patients were eligible for evaluation. Patients were split into four cohorts. One group of patients didn't receive any TIGIT treatment, while groups A, B and C received belrestotug at 100 mg, 400 mg and 1,000 mg, respectively. All patients received dostarlimab at 500 mg.  Clinically meaningful improvement in the overall response rate (ORR)—the trial’s primary endpoint—was seen across each TIGIT cohort, with a 63.3% ORR reported for group A, a 65.6% ORR seen for arm B and 76.7% for dose C. This compares with the 37.5% ORR observed for dostarlimab alone. The median follow-up time varied by arm, with dostarlimab at 7 months, group A and B both at 8.5 months and dose C at 6.7 months.The confirmed ORR (cORR), defined as a complete or partial response confirmed by repeat imaging at four or more weeks after the response criteria were first met, was about 60% for each dose. This is compared to a 28.1% cORR for dostarlimab as a monotherapy.The ORR and meaningful difference of 30% compared to dostarlimab by itself separates the TIGIT/PD-1 doublet from others, iTeos President and CEO Michel Detheux, Ph.D., said in a Sept. 14 release.“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 said. “Based on these results, we are committed to leveraging our science to impact the lives of people living with cancer and are excited to see progression free survival data in 2025.” As for safety, the investigational combo was tied to “a higher incidence of manageable immune-related adverse events,” compared to dostarlimab alone, according to the release. The most frequent treatment-related adverse events reported were skin and subcutaneous tissue disorders.The combo’s safety profile has been “broadly consistent” with the known profile of combination therapy with checkpoint inhibitors, according to iTeos.In May, GSK and iTeos announced that a positive interim analysis had bolstered confidence, prompting the companies to launch a phase 3 study called GALAXIES Lung-301 in the same setting. The companies didn’t reveal any data at the time, just noting that the investigational combo met the predefined criteria for meaningful clinical activity and tumor reductions.Dosing for GALAXIES Lung-301 started in July, with the trial expected to enroll around 1,000 patients. The study is testing the belrestotug-Jemperli combo against a placebo-Keytruda arm and has a primary completion date slated for 2028, according to ClinicalTrials.gov. The partners have not disclosed the dosing level of belrestotug in the phase 3 trial. Analyst group William Blair previously said it would be interested in comparing the findings to those from Roche’s phase 2 CITYSCAPE study in NSCLC. That study saw success combining Roche’s TIGIT tiragolumab with Tecentriq, with an objective response in 31.3% of patients versus 16.2% with Tecentriq plus placebo.However, Roche’s tiragolumab has hit trouble in late-stage trials, failing to hit the primary endpoint in a phase 3 SCLC study dubbed SKYSCRAPER-02. More recently, the Swiss pharma halted the SKYSCRAPER-06 study evaluating the combo plus chemotherapy in front-line nonsquamous NSCLC after the pair was beat by Keytruda and chemotherapy. Roche still has ongoing tiragolumab-Tecentriq studies, and even pocketed a win for the TIGIT in a phase 3 SKYSCRAPER-08 esophageal study, though the use of an outdated control therapy have left doubts about clinical significance.  However, the earlier flops shook TIGIT players, with GSK and iTeos assessing “how best to proceed with additional clinical development” of their rival asset after a phase 3 Roche flop in 2022. GSK paid iTeos $625 million upfront for the right to co-develop and co-commercialize belrestotug in 2021, tacking on up to $1.45 billion in milestones. While Roche’s setbacks may have led to some soul-searching, it doesn’t appear to have too big of an impact—belrestotug is currently being studied in six separate clinical trials.iTeos will be holding a call on at 8 a.m. ET regarding the data, according to the company release.

BARCELONA — GSK and iTeos have unveiled positive mid-phase data for their PD-1 plus TIGIT doublet in certain lung cancer patients, bolstering expectations for an ongoing Phase 3 trial that is testing the combination against Merck’s Keytruda. The readout is one of the first catalysts for iTeos “after years of lying low,” Leerink analysts said last month. It is also an opportunity for the Watertown, MA-based biotech to prove it has a best-in-class TIGIT drug amid broader investor pessimism for class, they added. The open-label Phase 2 GALAXIES Lung-201 trial set GSK’s Jemperli plus iTeos’ TIGIT drug belrestotug against Jemperli alone in people with previously untreated PD-L1 high locally advanced or metastatic non-small cell lung cancer (NSCLC).​ The primary endpoint was objective response rate (ORR) measured at up to 24 months. In the 124 patients evaluable at data cut-off, the doublet achieved a confirmed ORR of around 60% in all three dose cohorts compared with 28.1% for Jemperli monotherapy. The result represents a delta of more than 30 percentage points, according to data presented Saturday at the European Society of Medical Oncology annual meeting in Barcelona. Both figures were made up of partial responses, with no complete responses reported yet. If you compare these results with historical data for Keytruda, which is the standard of care, “we believe we have set up a new threshold for response rates in this patient population,” iTeos CEO Michel Detheux told Endpoints News in an interview ahead of the meeting. For context, a multicenter retrospective analysis of Keytruda monotherapy in 187 people with first-line, PD-L1 high NSCLC showed the drug achieved a 44.4% ORR. iTeos said adding belrestotug to Jemperli led to a rise in immune-related adverse events but these were manageable. The most common side effects associated with the doublet were skin and subcutaneous tissue disorders (50%) and endocrine disorders (26%), the company added. Back in June, GSK and iTeos kicked off the Phase 3 GALAXIES Lung-301 trial, which is testing Jemperli plus belrestotug against Keytruda plus placebo in the same patient population. The study will enroll around 1,000 participants and evaluate progression-free survival and overall survival as primary endpoints. “We think the [Phase 2] data is going to be critically important to help support a rapid readout that gets us closer every day to the ultimate [Phase 3] readout,” iTeos Chief Financial Officer Matthew Gall said in the same interview. GSK and iTeos first started collaborating on belrestotug under the terms of a 2021 deal that saw iTeos get $625 million upfront and the potential of up to $1.45 billion in milestones. In the real world, around 70% of patients with PD-L1 high NSCLC are treated with immunotherapy alone, according to iTeos. It’s this group that the biotech plans to target initially, although Detheux said there’s also potential for belrestotug to benefit PD-L1 low lung cancer patients in theory when combined with other agents, although this would require a biomarker strategy to select patients most likely to benefit. TIGIT drugs have been the subject of much skepticism following a spate of recent setbacks. Last month, Merck ended a late-stage test of its TIGIT candidate, vibostolimab, in small-cell lung cancer after it proved unlikely to succeed. Shortly before that, Bristol Myers Squibb returned a TIGIT bispecific drug to Agenus. In July, Roche’s tiragolumab failed to meet the primary endpoints in a Phase 2/3 lung cancer test. Detheux said belrestotug is differentiated from other candidates because of its potency in the signaling pathway and the “multifaceted” way in which it modulates immune responses, engaging with both TIGIT and the Fc gamma receptor.