In combination with Roche’s PD-L1 blocker Tecentriq, zanzalintinib bested Bayer’s Stivarga. Exelixis is positioning the drug candidate as a successor to cabozantinib, which is set to lose patent exclusivity in 2030.
Exelixis’ third-generation tyrosine kinase inhibitor zanzalintinib, when used in combination with Roche’s PD-L1 blocker Tecentriq, outperforms Bayer’s Stivarga for the treatment of certain patients with colorectal cancer, according to a release from Exelixis.
These findings, announced Sunday, mark “the first pivotal success from the zanzalintinib program,” William Blair analysts wrote in a Monday note. Exelixis did not provide specific data, noting only that the zanzalintinib combo significantly improved overall survival versus Stivarga in previously treated patients with metastatic colorectal cancer whose tumors have high levels of microsatellite instabilities.
Exelixis is up about 10% in Monday morning trading.
Zanzalintinib is an orally available tyrosine kinase inhibitor that blocks signaling pathways central to the growth and spread of cancer. Exelixis is positioning the investigational drug as a successor to cabozantinib, an oral drug marketed as Cabometyx for renal cell carcinoma and hepatocellular carcinoma and as Cometriq for medullary thyroid cancer.
Last year, the cabozantinib franchise hit $1.81 billion in net U.S. sales—earnings that could be at risk once the drug loses patent exclusivity in 2030.
“We think the topline success of this trial likely provides additional fundamental and strategic value to shares, suggesting [zanzalintinib] may be able to extend the company’s revenue stream beyond the [cabozantinib] loss of exclusivity in 2030,” analysts at Leerink Partners wrote of the new readout in a Monday note to investors.
Exelixis studied zanzalintinib in the open-label Phase III STELLAR-303 trial, which enrolled more than 900 patients. The survival benefit of the zanzalintinib regimen was observed in the study’s intention-to-treat (ITT) analysis, which encompasses all randomized participants regardless of liver metastases. According to William Blair, the ITT population represents “the largest commercial opportunity” for Exelixis, with risk-adjusted U.S. peak sales of $875 million.
STELLAR-303 did not report any new safety signals of concern.
Exelixis is also studying zanzalintinib in renal cell carcinoma (RCC) and head and neck cancer, for which Sunday’s STELLAR-303 readout could have some “incremental” positive read-through, Leerink added. Both programs have milestones in the back half of this year, the analysts noted, including a Phase III topline readout for RCC and a go/no-go decision for using zanzalintinib as a frontline therapy for head and neck cancer.
