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.
Michel DetheuxIf 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.
Matthew GallIn 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.