GSK Faces Setbacks in Oncology Pipeline as Anti-TIM-3 and Anti-TIGIT Programs Falter

GSK, the British pharmaceutical giant, has encountered significant challenges in its oncology pipeline, with two high-profile programs failing to meet expectations. The company's second-quarter earnings report revealed disappointing results for its anti-TIM-3 antibody cobolimab and the discontinuation of its anti-TIGIT antibody belrestotug, resulting in substantial financial implications.

Cobolimab Fails Phase 3 Trial in Non-Small Cell Lung Cancer

GSK's cobolimab, an anti-TIM-3 antibody acquired through the $5.1 billion Tesaro takeover in 2018, has failed to meet its primary endpoint in a crucial phase 3 study. The trial, which evaluated cobolimab in combination with GSK's oncology drug Jemperli and chemotherapy docetaxel, aimed to improve overall survival in advanced non-small cell lung cancer (NSCLC) patients who had previously received immuno-oncology therapies.

Despite the setback, GSK reported that all regimens were well-tolerated, with toxicities consistent with known safety profiles of docetaxel and immune checkpoint inhibitors. The company acknowledged the challenging nature of this treatment setting, where novel combinations have struggled to improve outcomes for most patients.

While the phase 3 failure is a significant blow, GSK continues to evaluate cobolimab in other settings. The drug remains under investigation in a phase 1/2 trial for various pediatric cancers and a midstage trial for advanced liver cancer.

Anti-TIGIT Program Discontinued, Resulting in $629 Million Impairment

In another setback for GSK's oncology efforts, the company announced the discontinuation of its anti-TIGIT antibody belrestotug. This decision has resulted in a substantial impairment charge of 471 million pounds sterling ($629 million).

GSK had initially acquired the rights to belrestotug four years ago, paying iTeos $625 million upfront. Following the phase 2 failure of belrestotug, iTeos planned to wind down operations before accepting a buyout offer from Concentra Biosciences earlier this month.

Broader Implications for the TIM-3 and TIGIT Landscapes

The failures of GSK's TIM-3 and TIGIT programs reflect broader challenges in these areas of cancer immunotherapy. Several other major pharmaceutical companies have also faced setbacks in their pursuit of TIM-3 and TIGIT-targeted therapies:

• Novartis's anti-TIM-3 candidate failed a late-stage study in myelodysplastic syndrome and leukemia in early 2024.
• Roche removed a PD-1xTIM-3 bispecific from its pipeline in 2022.
• Bristol Myers Squibb terminated a phase 1 trial of its TIM-3 candidate, BMS-986299, in 2022.
• Eli Lilly and Incyte have also discontinued their respective TIM-3 drugs.

Despite these setbacks, some companies continue to explore the potential of TIM-3 targeted therapies. AstraZeneca, for instance, still has a PD-1xTIM-3 bispecific in development, with a phase 1/2 study expected to complete this year.