BeiGene announced Thursday it will no longer pursue development of ociperlimab, its investigational anti-TIGIT antibody, after disappointing results in a Phase III lung cancer trial. The decision followed a pre-planned futility analysis of the AdvanTIG-302 study, where an independent data monitoring committee determined the therapy was "unlikely to meet the primary endpoint of overall survival" in patients with non-small cell lung cancer (NSCLC).
The company has not released specific data from the trial but indicated detailed results would be shared "at a later date." No new safety signals were reported in the announcement.
The Failed Trial Design
The AdvanTIG-302 study was a double-blind Phase III trial evaluating ociperlimab (BGB-A1217) plus tislelizumab versus pembrolizumab in adult patients with PD-L1-high, locally advanced, recurrent, or untreated metastatic NSCLC. Patients were randomized to receive either tislelizumab plus ociperlimab, pembrolizumab plus placebo, or tislelizumab plus placebo.
Treatment in the experimental arm consisted of tislelizumab at 200 mg intravenously plus ociperlimab at 900 mg intravenously once every three weeks. The trial's primary endpoint was overall survival, with secondary endpoints including progression-free survival, overall response rate, and duration of response.
"We evaluate our clinical programs to focus our resources on the most promising clinically differentiated candidates while thoughtfully de-prioritizing others," said Dr. Mark Lanasa, Chief Medical Officer for Solid Tumors at BeiGene. "Our commitment remains steadfast: to discover and develop innovative treatments that are more affordable and accessible to cancer patients worldwide."
Mechanism of Action and Development History
Ociperlimab is a humanized IgG1 monoclonal antibody designed to target the TIGIT receptor found on T cells and natural killer cells. When triggered, TIGIT suppresses immune cell activity, a pathway cancer cells exploit to evade immune response. By blocking this interaction, ociperlimab was intended to enhance immune system activity against cancer cells.
The drug's development history includes a significant partnership with Novartis, which paid BeiGene $300 million in December 2021 to license ociperlimab for North America, Europe, and Japan. At that time, BeiGene had an extensive development program for the molecule, with ongoing studies in NSCLC, cervical cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and other advanced solid tumors.
However, less than two years later, in July 2023, Novartis terminated the partnership after reviewing "the totality of the current information, including Phase II data, benefit/risk, competitive space, timing, development programs, and future investments." This withdrawal forced BeiGene to reevaluate its development strategy for ociperlimab.
Broader Challenges in the TIGIT Space
BeiGene's setback with ociperlimab adds to mounting challenges in the anti-TIGIT therapeutic landscape. In May 2024, Merck discontinued a Phase III study of its anti-TIGIT antibody vibostolimab in combination with Keytruda in patients with resected, high-risk melanoma, citing a high rate of toxicity-related dropouts. Months later, Merck terminated another late-stage trial of the same combination in NSCLC following recommendations from an independent data review panel.
These consecutive failures raise questions about the viability of TIGIT as a therapeutic target, despite its promising biological rationale. The pathway remains of interest to researchers, but developers may need to reconsider drug design, combination strategies, or patient selection criteria to overcome the challenges that have plagued recent clinical trials.
Impact on BeiGene's Pipeline
For BeiGene, the discontinuation of ociperlimab represents a significant setback to its immuno-oncology portfolio. The company will likely redirect resources to other promising candidates in its pipeline, including further development of tislelizumab, its PD-1 inhibitor marketed as Tevimbra.
The company's decision to terminate the program reflects the challenging reality of oncology drug development, where promising mechanisms of action don't always translate to clinical benefit. BeiGene's transparent approach to communicating trial failures aligns with growing industry emphasis on data integrity and responsible resource allocation in drug development.
