Exelixis/Roche Combo Fails to Improve Overall Survival in NSCLC

A combination of Exelixis’ cabozantinib and Roche’s Tecentriq missed the primary endpoint of overall survival in a Phase III study.

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Exelixis’ cancer portfolio stumbled Thursday as the Alameda, CA-based company reported that a Phase III study of cabozantinib in combination with Roche’s Tecentriq (atezolizumab) failed to hit the primary endpoint of overall survival in second-line non-small cell lung cancer.

In the CONTACT-01 study, 366 patients with squamous and non-squamous NSCLC were randomized 1:1 to receive cabozantinib in combination with Tecentriq versus docetaxel, a commonly used chemotherapy. All patients had progressed during or following treatment with anti-PD-1/PD-L1 therapy.

Exelixis reported no new safety signals and stated the safety profile was consistent with that of both cabozantinib and Tecentriq.

Exelixis plans to present further details of the study at a future medical meeting, according to the Thursday press release. Ipsen and Takeda were also involved in funding this trial per their collaboration agreements with Exelixis.

The Phase III trial did not follow the trajectory the partners had hoped for after the combination showed an objective response rate of 19% in Cohort 7 of the COSMIC-021 trial in patients with stage IV non-squamous NSCLC.

These results were presented at the 2022 American Society of Clinical Oncology (ASCO) annual meeting in June and Exelixis called the activity “encouraging.”

Cabozantinib (Cabometyx), a tyrosine kinase inhibitor, was approved by the FDA in January 2021 in tandem with Bristol Myers Squibb’s Opdivo in first-line advanced renal cell carcinoma.

The approval was granted on the strength of a “significant” overall survival advantage. At the time of the approval, median OS had not yet been reached in either the Cabometyx/Opdivo treatment arm or the comparative sunitinib cohort. Median progression-free survival was double that of sunitinib at 16.6 months versus 8.3 months.

Collaboration Spree

Exelixis made news in November with a series of collaborations. In the first, Exelxis gained the exclusive right to acquire CBX-12 (alphalex exatecan), a first-in-class peptide-drug conjugate from Cybrexa. Exelixis paid $60 million upfront for access to CBX-12.

In a second deal, Exelixis entered into an exclusive clinical development and option agreement with Netherlands-based Sairopa for ADU-1805. The monoclonal antibody targets signal regulatory protein alpha (SIRPα), in order to improve the immune system’s ability to attack tumors.

Finally, Exelixis struck an exclusive licensing agreement with Catalent for three target programs with antibody and antibody-drug conjugates.

At the time, Peter Lamb, Ph.D., Exelixis EVP, scientific strategy and chief scientific officer, said the targets have “broad potential” in a range of solid tumor indications including bladder, breast, lung, ovarian and pancreatic cancer.

With such a deep collaborative pipeline, the NSCLC flop cannot be expected to keep Exelixis down for long.

Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.