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Roche’s TIGIT drug tiragolumab fails Phase 3 lung cancer trial

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Roche will halt a late-stage study of tiragolumab after it failed to help certain lung cancer patients, adding to a string of registrational disappointments for the drug in recent years.

The anti-TIGIT drug candidate, combined with Roche’s PD-L1 drug Tecentriq and chemotherapy, did not meet the progression-free survival  and overall survival primary endpoints when compared to Merck’s Keytruda plus chemotherapy in the Phase 2/3 SKYSCRAPER-06 test. The trial enrolled first-line patients with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer.

The treatment arm showed “reduced efficacy” in both PFS and OS versus control in the intent-to-treat population, Roche said in a Thursday release. The company plans to unblind and end the trial, which enrolled 542 people with NSCLC, and “evaluate any relevant changes needed” to other trials in the tiragolumab program. It will also share the data with health authorities and present them at an upcoming medical meeting.

Roche’s share price on the Swiss stock exchange was down by more than 2% when the market opened Thursday.

The Swiss drugmaker’s registrational development program for tiragolumab has had very limited success to date. Back in 2022, tiragolumab plus Tecentriq missed the PFS co-primary endpoint in the Phase 3 SKYSCRAPER-01 test in first-line PD-L1 high NSCLC patients, although data later showed the treatment arm trended toward improvement in OS.

Earlier in 2022, tiragolumab as a single agent flunked the Phase 3 SKYSCRAPER-02 study in extensive-stage small cell lung cancer.

Things started to look better in January when the drug combined with Tecentriq and chemotherapy clinched a Phase 3 success versus chemotherapy and placebo in the SKYSCRAPER-08 trial of Asian patients with locally advanced, unresectable recurrent or metastatic esophageal squamous cell carcinoma. But by that time, standard of care for the disease setting had already evolved to include checkpoint inhibitors.

Elsewhere, the drug candidate is being given after Tecentriq versus Tecentriq plus placebo or placebo alone in the Phase 3 SKYSCRAPER-07 trial in esophageal cancer patients who have not progressed after chemoradiotherapy.

Several companies have been exiting or changing course in the TIGIT space of late, including Coherus BioSciences, which terminated a three-year pact on the target with Shanghai Junshi Biosciences in January after obtaining a separate TIGIT drug as part of its acquisition of Surface Oncology. Merck also recently shuttered a TIGIT/PD-1 combo trial due to safety-related dropouts.

In September, Bristol Myers Squibb axed a mid-stage anti-TIGIT program in solid tumors, although it’s continuing to work on an early-phase TIGIT bispecific.


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