A fresh flop in metastatic non-small cell lung cancer (NSCLC) marks the latest in a string of clinical losses for the pairing of Exelixis and Ipsen's tyrosine kinase inhibitor Cabometyx and Roche’s immuno-oncology star Tecentriq.
Friday, Ipsen issued a sparse press release revealing the combo missed the mark on its primary endpoint in the phase 3 study Contact-01. The 366-patient trial pitted Cabometyx and Tecentriq against the chemotherapy docetaxel in patients with unmutated NSCLC whose disease progressed on or after treatment with an immune checkpoint inhibitor and platinum chemotherapy.
To succeed, the combo needed to show it could help patients live longer than chemotherapy alone. Secondary endpoints in the study looked at measures such as progression-free survival, objective response rate and duration of response.
Detailed results weren’t included in the company’s release. Ipsen did not say whether the partners plan to continue developing the Cabometyx-Tecentriq combo in NSCLC.
Ipsen did note that the combo regimen’s side effect profile was on par with the drugs’ independent safety signals, with no new concerns emerging during the trial. The company added that it will submit detailed findings to present at a future medical meeting.
The results are a blow not just to Roche and Ipsen, but also Takeda and Exelixis, the original developer of Cabometyx. Exelixis has granted Ipsen rights to sell and develop the TKI inhibitor outside the U.S. and Japan, where Takeda holds a similar marketing and R&D deal.
In the U.S., the drug is approved alone and in combination with Bristol Myers Squibb’s Opdivo for renal cell carcinoma. It’s also approved as a monotherapy in hepatocellular carcinoma and thyroid cancer.
The trial update comes as a “disappointment,” and likely spells the end for the combo in this indication—though the financial “consequences are limited,” ODDO BHF analysts wrote in a note to clients Friday.
Given the prevalence of the form of cancer represented in Contact-01, today’s outcome likely “prevents any potential” for Cabometyx in that disease, they added.
A Roche spokesperson said the update is "disappointing, particularly in this difficult to treat setting where people have already experienced disease progression following previous therapies."
Roche remains "committed to addressing the numerous unmet needs to provide an effective treatment option for every person with lung cancer," she said over email Monday. Learnings from the CONTACT-01 study "will be used to inform existing and future studies for Tecentriq in lung cancer," she added.
This isn’t the first time the Roche and Ipsen combo has stumbled this year. Back in March, Cabometyx and Tecentriq dropped the ball in a phase 3 study against Bayer’s Nexavar in newly-diagnosed liver cancer, prompting Exelixis to call it quits on plans for a Cabometyx label expansion in that use.
That trial loss came on the heels of the combo’s surprise failure to prolong the lives of patients with previously untreated hepatocellular carcinoma—the most common type of liver cancer—back in June 2021.
Last year’s trial failure came as something of a shock, given Cabometyx and Tecentriq’s previous liver cancer wins. Cabometyx has been approved in previously-treated liver cancer since early 2019, while Tecentriq plus Roche’s Avastin in 2020 became the first immuno-oncology therapy approved for newly diagnosed patients.
Editor's note: This story has been updated with comments from Roche