The recent failure of a Phase 3 clinical trial has led Gilead Sciences and Arcus Biosciences to halt a mid-stage study of their investigational TIGIT drug, domvanalimab, designed for lung cancer treatment. This decision marks a significant setback for both companies and initiates a reevaluation of their longstanding partnership.
Trial Outcomes Prompt Discontinuation
Gilead and Arcus have announced the discontinuation of the STAR-121 trial, which was assessing the efficacy of domvanalimab when combined with a PD-1 blocker and chemotherapy for metastatic non-small cell lung cancer (NSCLC). The study’s independent data monitoring committee concluded that the trial was futile, especially in comparison to Merck’s Keytruda combined with chemotherapy. Although safety assessments were performed regularly, the latest futility analysis did not include new safety concerns.
Impact on Collaboration
This recent setback has prompted Gilead to withdraw from its cancer collaboration with Arcus, which has been ongoing for several years. Following the announcement, Arcus disclosed in a securities filing that Gilead opted not to proceed with an option continuation payment. This decision effectively terminates Gilead’s access to a range of early-stage TIGIT therapies and will officially end its involvement in the development of new Arcus programs by July 14.
Retained Interests
Despite the setbacks, Gilead will maintain certain existing options related to specific programs such as the small-molecule AXL blocker AB801, the anti-CD39 antibody AB598, and the MRGPRX2 antagonist AB102. However, the exact timelines for these options’ expiration remain unspecified.
Further Trial Cancellations
The failure of the STAR-121 trial has also led to the termination of the Phase 2 EDGE-Lung study, which was similarly assessing domvanalimab in NSCLC. This series of failures marks a significant downturn for Gilead and Arcus, shaking the foundation of their collaboration that began in May 2020 to develop next-generation cancer therapies centered around TIGIT programs.
Initial Successes and Industry Context
Initially, Gilead and Arcus experienced some success with their TIGIT programs, even as other companies faced challenges. For instance, data from the Phase 2 EDGE-Gastric study released in June 2024 revealed a notable 58.5% overall response rate in patients with upper gastrointestinal cancers treated with domvanalimab and an anti-PD-1 therapy.
However, the broader landscape for TIGIT therapies has been tumultuous. Other companies like Roche and Merck have faced similar failures with their respective TIGIT candidates, leading to the abandonment of late-stage studies. Last year, GSK and iTeos Therapeutics also halted their TIGIT therapy, belrestotug, following disappointing results.
Financial Implications
The challenges in the TIGIT class have not only resulted in clinical failures but have also led to considerable financial losses. An analysis indicates that companies have collectively invested at least $1.4 billion in upfront costs related to TIGIT partnerships, with many of these investments yielding no returns. Potential milestone payments, which could total $5 billion, remain largely unpaid.
Conclusion
The recent trials have highlighted the unpredictable nature of drug development in oncology, particularly within the TIGIT landscape. As Gilead and Arcus navigate these challenges, the future of their collaboration and the potential of TIGIT therapies remain uncertain. The industry will be closely watching how both companies adapt to these setbacks and what their next steps will be in the evolving landscape of cancer treatment.
- Gilead and Arcus halt key TIGIT trial due to futility.
- The partnership faces significant challenges as a result.
- Financial implications of clinical failures are substantial.
- The broader landscape for TIGIT therapies is under scrutiny.
- Future collaborations and developments remain uncertain.
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