GSK has suffered a significant setback in its oncology pipeline after its anti-TIM-3 monoclonal antibody cobolimab failed to meet the primary endpoint in a Phase III trial for advanced non-small cell lung cancer (NSCLC). The COSTAR study was unable to demonstrate improved overall survival in patients previously treated with PD-1/PD-L1 inhibitor-based cancer immunotherapies.
Trial Design and Results
The COSTAR Lung study (NCT04655976) compared three treatment arms: a triple therapy combination of cobolimab, Jemperli (dostarlimab), and docetaxel; a double combination of dostarlimab and docetaxel; and docetaxel alone. Neither the triple nor double combination therapy met the primary efficacy endpoint of overall survival in advanced NSCLC patients.
According to GSK, all treatment regimens were well tolerated, with toxicities consistent with the known safety profiles of docetaxel and immune checkpoint inhibitors. The company has not disclosed whether the study met any secondary endpoints, including objective response rate, progression-free survival, or duration of response.
Broader TIM-3 Development Challenges
The failure represents another disappointment in the challenging field of TIM-3 checkpoint inhibition. GSK acknowledged that advanced NSCLC "remains a challenging treatment setting where novel combinations have yet to improve outcomes for most patients."
This setback is particularly notable given that cobolimab showed promise in Phase II studies using the same triple combination approach. The drug was acquired by GSK as part of its $5.1 billion takeover of Tesaro in 2018.
Industry-Wide TIM-3 Struggles
GSK joins a growing list of pharmaceutical companies facing difficulties with TIM-3-targeted therapies. In early 2024, Novartis ended development of its TIM-3 antibody sabatolimab in myelodysplastic syndromes after a disappointing late-stage trial readout. The company had also been testing sabatolimab in acute myeloid leukemia.
Other discontinued TIM-3 programs include Roche's TIM-3/PD-1 inhibitor bispecific antibody RO7121661, Bristol Myers Squibb's antibody-based drugs developed with Five Prime, a bispecific from Eli Lilly, and an Incyte antibody. Bristol Myers Squibb also discontinued its TIM-3 candidate BMS-986299 from Phase I trials in 2022.
Financial Impact and Future Plans
GSK took a £471 million ($630 million) charge in the second quarter related to its decision to abandon another checkpoint inhibitor program targeting TIGIT, including ending its alliance with iTeos for belrestotug development.
Despite the COSTAR failure, cobolimab remains in Phase II studies for liver cancer, cervical cancer, and melanoma, according to the clinicaltrials.gov registry. However, GSK has not provided guidance on whether it intends to continue the drug's development, and only the NSCLC trial appears in the company's current pipeline listing.
Market Context
The NSCLC market across seven major markets is predicted to reach $56.5 billion by 2032, according to GlobalData. PD-1/PD-L1 and CTLA-4 inhibitors, including Merck's Keytruda (pembrolizumab) and Bristol Myers Squibb's Opdivo (nivolumab), are forecast to generate $21.9 billion in sales by 2032. EGFR inhibitors such as AstraZeneca's Tagrisso (osimertinib) and Johnson & Johnson's Rybrevant (amivantamab-vmjw) are expected to contribute $8.6 billion in the same timeframe.
Despite the clinical setback, GSK reported strong financial performance with £8 billion in second-quarter sales, representing 6% growth that exceeded analyst consensus estimates. CEO Emma Walmsley expressed confidence in the company's outlook, stating: "With the breadth of our current business and the growth opportunities we have in our pipeline, we are highly confident in our outlook for sales of more than £40 billion by 2031."
