- Roche is betting a new type of cancer immunotherapy could help to improve on the benefit offered by the first generation of immune-boosting drugs. Preliminary study results unveiled for the first time Wednesday give some reason for optimism in the Swiss drugmaker's approach, although the data fall short of showing a clear advantage over existing drug combinations.
- The results, included in a trial abstract released ahead of the American Society of Clinical Oncology's virtual meeting later this month, suggest adding Roche's experimental drug tiragolumab to its approved immunotherapy Tecentriq is more effective than Tecentriq alone in treating people with advanced lung cancer.
- Wednesday's data offer the first substantive look at how well tiragolumab works. Roche executives have talked up the drug's potential at recent events, raising expectations that it, along with other drugs that work similarly, could offer a path to amplify the tumor-killing effects of immunotherapies like Tecentriq.
For several years now, drugmakers have hunted for a way to improve on cancer immunotherapy, which, while strikingly effective in some, still doesn't benefit most patients.
Their quest has run into several dead-ends in the nearly 10 years since the U.S. approval of Bristol Myers Squibb's Yervoy, a therapeutic cousin to Bristol Myers' Opdivo and Merck & Co.'s now dominant Keytruda. All three work by blocking proteins that dampen the body's immune response to tumor cells — CTLA4 in the case of Yervoy and PD-1 in the case of Opdivo and Keytruda.
With tiragolumab, Roche is targeting another inhibitor protein called TIGIT that the company's researchers discovered in its Genentech laboratories. The pharma argues that blocking TIGIT and PD-L1, a related ligand of PD-1, together will result in greater tumor control than either drug would alone.
The data released Wednesday are from a Phase 2 study of 135 patients with non-small cell lung cancer who tested positive for PD-L1.
Treatment with tiragolumab and Tecentriq together shrank tumors in a little less than a third of previously untreated patients with metastatic lung cancer, results showed. That's double the 16% response rate observed with Tecentriq alone, and compares with a 27% response rate for Keytruda in a similar group of patients. But, it's well below the response rates to Keytruda when paired with chemotherapy, a drug regimen which has become a standard treatment for most lung cancer patients.
Measured by how long patients went without their tumors growing, treatment with the two-drug combination resulted in a median progression-free survival of 5.4 months compared to 3.6 months for Tecentriq.
While the combination bested Tecentriq, investors and cancer specialists polled by Cowen & Co. at a 2020 conference indicated they were expecting to see response rates in a higher range of between 40% and 60%.
Tiragolumab's benefit in patients with higher levels of PD-L1 might offer greater grounds for optimism. In that smaller subset of 58 patients, 55% given the combination saw their tumors shrink, versus only 17% who received Tecentriq.
The frequency of side effects was similar between the two groups, Roche said.
Interest in TIGIT as a potential drug target has grown over the past two years, and some half dozen therapies aimed at the receptor are now in various stages of clinical development across the industry. Last month, Gilead was rumored to be in talks to buy Arcus Biosciences, a small biotech also exploring TIGIT, but no deal ever emerged.
Outside of an early update from Merck in the fall of 2018, however, little clinical data has ever been presented on a TIGIT-targeting compound, making Roche's data of particular interest.
In February, Daina Graybosch, an analyst at SVB Leerink, called Roche's study "arguably the biggest test of synergy" between two cancer immunotherapies since a 2018 failure of an Incyte drug that many had hoped would signal a path forward for the field.
Since then, another big bet by Bristol Myers on an IL-2 targeting drug from Nektar Therapeutics also disappointed, spurring further caution to runaway expectations for the success of immunotherapy combinations.
With TIGIT, however, Roche appears convinced. The pharma has recently launched two Phase 3 studies testing tiragolumab and Tecentriq in two types of lung cancer. Tiragolumab is also being tested in "umbrella" studies of multiple drugs in pancreatic, esophageal and bladder cancer.
Merck too is advancing studies of its own TIGIT compound, dubbed MK-7684.
Correction: A previous version of this article incorrectly referred to PD-1, rather than PD-L1 in the third paragraph.