Roche, Exelixis' Tecentriq-Cabometyx pair fails again—this time in kidney cancer

Roche and Exelixis’ combination of Tecentriq and Cabometyx just can't win. After stumbling in liver cancer and lung cancer, the regimen has failed again.

Pairing Tecentriq with Cabometyx couldn’t further stave off cancer progression or death compared with Cabometyx alone in kidney cancer patients who’ve progressed on initial immunotherapy. The negative result came from the phase 3 Contact-03 trial. Exelixis announced the flop Thursday in a short release without many details other than stating that the data will be presented at an upcoming conference.

Exelixis’ stock price at some point dropped nearly 9% because of the news during after-hours trading on Thursday. The price decreased about 4% Friday morning. But William Blair analyst Andy Hsieh, Ph.D., argued that investors were overreacting. To Hsieh, the trial flop has a different significance for each drug.

The combo’s flop, depending on detailed data, may buttress Cabometyx as the most appropriate tyrosine kinase inhibitor (TKI) in kidney cancer, Hsieh said. Before Contact-03’s readout, Calithera Biosciences’ now-discontinued glutaminase inhibitor telaglenastat also failed to improve upon Cabometyx in a randomized clinical trial, he noted. 

A success would likely mean a relatively small addition to Cabometyx’s business anyway, given the drug already holds about half of the second-line market share, Hsieh noted. The TKI earned its initial approval in 2016 in previously treated kidney cancer following anti-angiogenic therapy. Besides, Roche is actually the sponsor of Contact-03, whereas Exelixis is a collaborator.

For Roche, Contact-03 may add to the growing body of evidence that suggests PD-L1 inhibitors such as Tecentriq could be inferior to their anti-PD-1 counterparts at least in kidney cancer, Hsieh said.

Combining PD-1 or PD-L1 inhibitors and TKIs have been widely adopted in newly diagnosed kidney cancer. FDA-approved therapies in the frontline setting include Cabometyx coupled with Bristol Myers Squibb’s PD-1 inhibitor Opdivo. Merck & Co. and Eisai’s pairing of Keytruda and Lenvima is also viewed as a strong regimen, whereas Pfizer and Merck KGaA’s combination of PD-L1 inhibitor Bavencio and TKI Inlyta wasn’t competitive.

Exelixis recently partnered with BMS for Opdivo again in kidney cancer. The biotech in December 2022 launched Stellar-304, a phase 3 trial evaluating its next-generation TKI zanzalintinib in tandem with Opdivo in advanced non-clear cell renal cell carcinoma.

Contact-03’s flop comes after two other trial setbacks for the Tecentriq-Cabometyx combo. In a similar failure that showed adding Cabometyx probably wouldn’t resensitize tumors to immunotherapy treatment, the Tecentriq-Cabometyx pairing didn’t help non-small cell lung cancer patients who had progressed on or after PD-1/L1 inhibitors in the Contact-01 trial. In 2021, the regimen also failed to beat Bayer’s Nexavar in previously untreated liver cancer.

Roche and Exelixis are also collaborating on Contact-02, testing whether Tecentriq and Cabometyx could beat either Astellas and Pfizer’s Xtandi or Johnson & Johnson’s Zytiga in previously treated metastatic castration-resistant prostate cancer. The study bears a primary completion date in June.