If at first you don’t entirely succeed, try your immune-boosting cancer drug in combination with another treatment. That seems to be the motto driving much of immuno-oncology research these days, and now Roche is adding another combo trial for its checkpoint inhibitor, Tecentriq.
Massachusetts-based Tesaro announced Monday that it will test its PARP inhibitor Zejula alongside Tecentriq in patients with metastatic bladder cancer. Roche unit Genentech, which initially nabbed FDA approval for Tecentriq as a second-line bladder cancer treatment in 2016, will launch the combo trial midyear, according to the Tesaro statement.
Tecentriq, which inhibits the immune checkpoint PD-L1, won an additional approval from the FDA last year for the first-line treatment of patients with advanced bladder cancer who are not eligible for cisplatin chemotherapy. But then the drug failed to show it could prolong patients’ lives in a phase 3 trial, raising questions about the true value of Tecentriq in bladder cancer—and that of other PD-1/L1 inhibitors.
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Roche didn’t lose its FDA approval in first-line bladder cancer as a result of the disappointing trial, but it did cede some market share. Barclays analysts reported in October that use of Tecentriq in bladder cancer was declining, with Roche’s share of the market losing ground to Merck’s Keytruda, which was approved last May for both first-line and second-line use in bladder cancer. Merck’s market position was boosted by one of its second-line trials showing that Keytruda extended overall survival by 10.3 months, vs. just 7.4 months for patients on chemo.
But Keytruda is far from the only challenger facing Tecentriq in the bladder cancer market. AstraZeneca picked up FDA approval in bladder cancer for its checkpoint inhibitor, Imfinzi, as did Merck KGaA and Pfizer for their entrant, Bavencio—and they all hit the market at around the same time last spring.
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Now it’s time for the influx of combo trials. The idea behind combinations is to boost the immune system’s ability to recognize and attack cancer beyond what can be achieved with monotherapy—ideally extending survival and expanding the population of patients who respond to immuno-oncology treatments. Pairing Tecentriq with Tesaro’s PARP inhibitor “could provide a potential option for patients with advanced bladder cancer, for whom mechanisms of immune escape, despite significant recent advances with anti-PD(L)-1 agents, remain a clinically relevant unmet need,” said Mary Lynne Hedley, Ph.D., president and COO of Tesaro, in the statement.
That said, there will be just as much competition in the race for good bladder cancer combos as there has been in the monotherapy market. Keytruda is being tested in combination with chemotherapy as a first-line bladder cancer treatment, for example, and Imfinzi is in testing along with a drug that blocks the checkpoint CTLA-4.
And plenty of companies are testing the PARP-PD-1/L1 theory in other cancers. Last summer, Merck and AstraZeneca inked an $8.5 billion partnership partly centered on testing combos of AZ’s PARP inhibitor Lynparza and both companies’ checkpoint inhibitors. Clovis Oncology teamed up with Bristol-Myers Squibb to pair Clovis’ PARP inhibitor Rubraca with BMS’s PD-1 blocker Opdivo in prostate, breast and ovarian cancer trials.
As for Tesaro, its alliance with Roche in bladder cancer could take it a long way toward meeting high expectations for Zejula. The drug is approved to treat ovarian, fallopian tube, or primary peritoneal cancer, and it brought in $65.3 million in sales in the first nine months of 2017. Analysts are expecting sales of the product to hit $1.9 billion a year by 2022. Zejula’s growth prospects will no doubt be a major topic of conversation during Tesaro’s full-year 2017 earnings report later Tuesday afternoon.