GSK, iTeos Revive TIGIT Field with Positive Phase 2 Jemperli Combo Data in Lung Cancer

GSK and iTeos have announced encouraging mid-phase results for their combination therapy of PD-1 and TIGIT inhibitors in specific lung cancer patients. This positive outcome supports the upcoming Phase 3 trial, which compares the combination therapy to Merck’s Keytruda.

The recently released data is a significant milestone for iTeos, a Watertown, MA-based biotechnology company that has been relatively quiet in recent years. Leerink analysts describe this as a potential turning point for the company, which aims to demonstrate that it possesses a superior TIGIT drug despite general investor skepticism about this class of drugs.

The open-label Phase 2 GALAXIES Lung-201 trial evaluated GSK’s Jemperli combined with iTeos’ TIGIT inhibitor belrestotug, against Jemperli alone in patients with previously untreated, PD-L1 high, locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary metric was the objective response rate (ORR) within a 24-month timeframe.

Among the 124 patients assessed at the data cut-off point, the combination therapy exhibited a confirmed ORR of approximately 60% across three different dose levels. In contrast, Jemperli monotherapy showed an ORR of 28.1%. This marks a notable improvement of over 30 percentage points, based on data shared at the European Society of Medical Oncology annual meeting in Barcelona. Both results were based on partial responses, as no complete responses were reported.

Comparing these outcomes with historical data for Keytruda, the current standard of care, iTeos CEO Michel Detheux expressed confidence in having established a new benchmark for response rates in this patient group. A retrospective analysis of Keytruda monotherapy in 187 patients with first-line, PD-L1 high NSCLC showed an ORR of 44.4%.

Adding belrestotug to Jemperli did lead to an increase in immune-related adverse events, but these were manageable. The most frequent side effects were skin and subcutaneous tissue disorders (50%) and endocrine disorders (26%).

In June, GSK and iTeos initiated the Phase 3 GALAXIES Lung-301 trial, which will compare Jemperli plus belrestotug against Keytruda plus placebo. The trial aims to enroll around 1,000 participants and will assess both progression-free survival and overall survival as primary endpoints.

Matthew Gall, iTeos Chief Financial Officer, emphasized the importance of the Phase 2 data in accelerating progress towards the Phase 3 readout. GSK and iTeos began collaborating on belrestotug in 2021, under an agreement that provided iTeos with $625 million upfront and the potential for up to $1.45 billion in milestone payments.

According to iTeos, approximately 70% of patients with PD-L1 high NSCLC are currently treated with immunotherapy alone. This is the initial target group for belrestotug. However, Detheux sees potential for the drug to benefit PD-L1 low lung cancer patients when combined with other agents, pending the development of a biomarker strategy to identify the patients most likely to benefit.

The TIGIT drug class has faced skepticism due to several recent failures. Last month, Merck halted a late-stage trial of its TIGIT candidate, vibostolimab, in small-cell lung cancer due to poor prospects. Similarly, Bristol Myers Squibb returned a TIGIT bispecific drug to Agenus, and Roche’s tiragolumab did not meet the primary endpoints in a Phase 2/3 lung cancer trial.

Detheux argues that belrestotug stands out from other TIGIT candidates due to its strong signaling pathway and its “multifaceted” approach to modulating immune responses, engaging both TIGIT and the Fc gamma receptor.