Roche, Exelixis Suffer Another Late-Stage Cancer Combo Failure

Photo of Exelixis building/company courtesy

Pictured: an Exelixis building/Company courtesy

Data from the Phase III CONTACT-03 study showed the combination of Roche’s Tecentriq (atezolizumab) and Exelixis’ Cabometyx (cabozantinib) fell short of its primary endpoint of progression-free survival in renal cell carcinoma (RCC).

While details were sparse, Exelixis reported Thursday that the Cabometyx-Tecentriq combination failed to significantly improve PFS in patients with locally advanced, metastatic clear cell or non-clear RCC, when compared with Cabometyx alone.

The company will present full findings and analyses at an upcoming medical meeting.

CONTACT-03 is a randomized and open-label study that enrolled 522 participants to determine whether a multi-tyrosine kinase inhibitor combined with an immune checkpoint inhibitor had clinical benefit in RCC after disease progression.

Aside from PFS, CONTACT-03 also evaluated overall survival, though data were immature at the time of the interim analysis, a Roche spokesperson told BioSpace.

The combination treatment had a safety profile consistent with the known side effects for the individual agents. No new safety signals were identified.

Roche and Exelixis entered into a clinical trial collaboration in 2017 when the two initiated a Phase Ib dose-escalation study to assess the safety and tolerability of the combination treatment in locally advanced or metastatic solid tumors.

The partnership is built on the synergistic promise between the two therapies. Cabometyx is a tyrosine kinase inhibitor that, in pre-clinical studies, has been shown to foster an “immunopermissive environment,” according to Exelixis, making tumor cells more sensitive to immune responses. 

This mechanism of action makes Cabometyx a good candidate for combination therapy with an immune agent such as Tecentriq, a monoclonal antibody that inhibits the PD-1/PD-L1 pathway and facilitates a stronger cytotoxic immune response.

Over the years, however, this synergy has yielded mixed results.

In December 2022, Roche and Exelixis suffered a late-stage defeat when the regimen failed to improve overall survival in the Phase III CONTACT-01 study in non-small cell lung cancer. The combo was given as a second-line treatment and compared against the combination of Cabometyx and docetaxel.

More promising results have recently emerged from the combination of Cabometyx and Bristol Myers Squibb’s Opdivo (nivolumab).

In February, three-year follow-up data from the Phase III CheckMate -9ER study showed Cabometyx could induce long-term survival and response rates in RCC when given as a front-line treatment with Opdivo. The treatment combination was compared against Pfizer's Sutent (sunitinib).

In January 2021, the FDA approved the combination of Cabometyx and Opdivo for the first-line treatment of advanced renal cell carcinoma. Cabometyx is also indicated as a monotherapy for previously untreated advanced renal cell carcinoma.

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