Tislelizumab

What was once a promising area of cancer immunotherapy has had another late-stage failure. BeiGene said Thursday that a Phase 3 study for its anti-TIGIT drug, called ociperlimab, was halted for futility after a recommendation from the trial’s independent data monitoring committee. The study’s primary endpoint was overall survival in patients with certain forms of metastatic non-small cell lung cancer. BeiGene has now elected to terminate development of ociperlimab. Researchers were testing a combination of BeiGene’s PD-1 inhibitor Tevimbra with ociperlimab against Merck’s Keytruda. A third study arm also administered Tevimbra as an active comparator. There were no new safety signals, BeiGene said in a release. The failure is the latest in a long-running list of recent TIGIT flops. Last year, Roche and Merck reported late-stage misses for their TIGIT programs, and Merck announced in December that it was discontinuing its drug. Bristol Myers Squibb returned the rights of a partnered TIGIT program to Agenus last year, and Gilead reworked a deal with Arcus to leave TIGIT out of their collaboration. Additionally, ociperlimab’s miss wasn’t the first time it ran into headwinds. Back in 2023, Novartis backed out of a partnership with BeiGene for the program. There is still some hope for the field. GSK and iTeos said in September that an anti-TIGIT drug combined with the PD-1 inhibitor Jemperli improved overall response rates in an advanced form of lung cancer. But the buzz is considerably smaller than a few years ago, when money was flowing toward research into these drugs.

iStock, Liudmila Chernetska An independent data monitoring board found that BeiGene’s ociperlimab was unlikely to significantly boost overall survival in patients with untreated NSCLC. BeiGene will no longer invest in its anti-TIGIT therapy ociperlimab, which it had been developing as a treatment for lung cancer, the biotech announced Thursday. The decision to discontinue ociperlimab’s development was driven by the results of a pre-planned futility analysis for BeiGene’s ongoing Phase III AdvanTIG-302 study in non-small cell lung cancer (NSCLC). An independent data monitoring committee found that ociperlimab was “unlikely to meet the primary endpoint of overall survival,” as per the biotech’s news release. BeiGene did not provide specific data from AdvanTIG-302 in its Thursday announcement but promised to do so “at a later date.” Ociperlimab is a humanized IgG1 monoclonal antibody that belongs to a class of checkpoint inhibitor drugs called anti-TIGIT therapies . These molecules work by targeting the TIGIT receptor, which is found on T cells and natural killer cells and which, when triggered, suppresses the activity of these cells. Cancer cells exploit this pathway to weaken and escape the immune response. In December 2021, Novartis paid BeiGene $300 million to license ociperlimab, giving it the right to develop, manufacture and commercialize the anti-TIGIT asset in North America, Europe and Japan. At the 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. Less than two years later, in July 2023, Novartis backed out of the deal after looking at “the totality of the current information, including Phase II data, benefit/risk, competitive space, timing, development programs, and future investments,” Fierce Biotech reported at the time, citing a company spokesperson. Losing a powerhouse partner forced BeiGene to “carefully evaluate all available data to inform future development opportunities with ociperlimab,” the biotech said in an SEC filing at the time, also noting that it was discontinuing one NSCLC study that combined ociperlimab with its own PD-1 blocker tislelizumab and pitted the combination against AstraZeneca’s Imfinzi. The broader TIGIT space has suffered several setbacks in recent months. In May 2024, citing a high rate of toxicity-related dropouts, Merck discontinued a Phase III study of its anti-TIGIT antibody vibostolimab, which it was trialing in combination with Keytruda in patients with resected, high-risk melanoma. A few months later, the pharma axed another late-stage trial of vibostolimab plus Keytruda in NSCLC, this time as per the recommendation of an independent data review panel. In July 2024, Roche also terminated a Phase II/III study for its anti-TIGIT therapy tiragolumab in NSCLC after a disappointing survival readout. Meanwhile, BMS in August 2024 abandoned its TIGIT pact with Agenus as part of a strategic push.