- A drug combination including Roche’s experimental immunotherapy tiragolumab failed one of two main goals in a Phase 3 trial in a common form of lung cancer, a setback that casts doubt on the potential of a closely watched group of medicines aimed at a cellular target called TIGIT.
- In an interim look at a study known as SKYSCRAPER-01, investigators found tiragolumab and a second Roche immunotherapy, Tecentriq, didn’t meaningfully slow tumor progression compared to Tecentriq alone in patients with advanced, newly diagnosed non-small cell lung cancer. The study will continue to the next analysis to assess whether the drug combination extends survival, its other main goal.
- Tiragolumab has now fallen short in two Phase 3 lung cancer trials, having already missed its study objectives in a particularly tough-to-treat form of the disease in March. Roche remains committed to the drug and noted in a statement Wednesday that a “numerical improvement” was observed on both study goals. The rest of its studies in other tumor types will continue as planned, Roche said.
Tiragolumab is closely watched by drugmakers, investors and Wall Street analysts. It’s the most advanced prospect among a group of medicines with high expectations, viewed as having potential to extend the reach of cancer immunotherapy.
That goal has been particularly tough for drugmakers to achieve. Companies have so far largely relied on chemotherapy and other targeted medicines to boost the effects of immunotherapy. While Bristol Myers Squibb won approval of a new kind of immunotherapy in March, such successes have been rare. Several high-profile immunotherapy combinations have failed in late-stage testing in recent years after showing early promise.
These setbacks often occurred after drugmakers “aggressively pursued development with minimal early-phase data,” wrote Daina Graybosch, an analyst at SVB Securities, in a note Wednesday. Roche didn’t, “derisking” the drug, Graybosch wrote, by taking a "traditional approach" and recording positive results in a placebo-controlled, Phase 2 study.
Those results, combined with encouraging findings from a rival program from Merck & Co., made immunotherapies aimed at TIGIT seem like a surer bet. GlaxoSmithKline, Bristol Myers and Gilead each recently acquired TIGIT-targeted drugs that are in human trials.
Those programs could face greater scrutiny now that Roche’s program — the first to reach Phase 3 testing — has had two significant setbacks since March.
Wall Street analysts had low expectations for the first study, in extensive small cell lung cancer, because it’s an aggressive form of the disease that's historically harder to treat. Roche also didn’t limit enrollment to only those patients who are viewed by many as most likely to benefit from immunotherapy.
Anticipation was greater for SKYSCRAPER-01. Roche enrolled 534 patients with high levels of the protein PD-L1, a group who responded well to treatment in its Phase 2 trial. Immunotherapies have also had notable successes in non-small cell lung cancer, for which drugs like Merck’s Keytruda and Roche’s Tecentriq are now considered standard treatments.
Roche's study still has a chance to succeed if the trends reported at the first interim analysis translate to a survival benefit over time. Nonetheless, the results are a blow to Roche, which is relying heavily on tiragolumab combinations to compete. They are also "likely to cast doubt on whether the TIGIT class has additive efficacy in oncology, and on the translatability of early data to later-stage trials," wrote Brian Abrahams, an analyst at RBC Capital Markets.
Yet, Umer Raffat, an analyst at Evercore ISI, argued in a note to clients Wednesday that the way Roche designed its statistical analysis for SKYSCRAPER-01 might mean there's still a chance results turn positive later on.
Share prices of Arcus Biosciences and iTeos, two TIGIT drug developers respectively aligned with Gilead and GSK, dropped significantly in premarket trading Wednesday.
Two other Phase 3 study results of tiragolumab are expected this year in esophageal and cervical cancers. Arcus, meanwhile, is expecting data from a mid-stage trial in 2022 and earlier this week said, without specifics, that a combination involving its TIGIT blocker “continued to show meaningful differentiation” from the control group in that study.