Exelixis' Zanzalintinib Outperforms Bayer's Stivarga in Pivotal Colorectal Cancer Trial

Exelixis has announced a significant victory in the field of colorectal cancer treatment, as its experimental drug zanzalintinib, in combination with Roche's PD-L1 inhibitor Tecentriq, has demonstrated superior overall survival compared to Bayer's Stivarga in a pivotal Phase III trial. This breakthrough marks a crucial step forward for Exelixis as it positions zanzalintinib to potentially succeed its flagship oncology medicine, Cabometyx.

STELLAR-303 Trial Results and Implications

The open-label Phase III STELLAR-303 trial, which enrolled over 900 patients, evaluated zanzalintinib in combination with Tecentriq against Stivarga in previously treated patients with metastatic colorectal cancer. The study focused on patients whose tumors exhibit high levels of microsatellite instabilities, a key subgroup in colorectal cancer treatment.

While specific data points were not disclosed, Exelixis reported that the zanzalintinib combination significantly improved overall survival compared to Stivarga. This improvement was observed in the intention-to-treat (ITT) analysis, which includes all randomized participants regardless of liver metastases status. According to William Blair analysts, the ITT population represents the largest commercial opportunity for Exelixis, with estimated risk-adjusted U.S. peak sales of $875 million.

Importantly, the STELLAR-303 trial did not reveal any new safety concerns for zanzalintinib, further solidifying its potential as a viable treatment option.

Strategic Implications for Exelixis

Zanzalintinib, an orally available tyrosine kinase inhibitor, is being developed as a successor to cabozantinib, which is marketed as Cabometyx for renal cell carcinoma and hepatocellular carcinoma, and as Cometriq for medullary thyroid cancer. With cabozantinib set to lose patent exclusivity in 2030, the success of zanzalintinib is crucial for Exelixis' long-term strategy.

The cabozantinib franchise generated $1.81 billion in net U.S. sales last year, underscoring the significant market potential for its successor. Exelixis has set ambitious goals for zanzalintinib, aiming to develop it into a $5 billion-a-year product by 2033. To achieve this, the company is targeting a broader range of indications, with gastrointestinal cancers, including colorectal tumors, expected to account for 45% of projected sales.

In response to the positive trial results, Exelixis' stock price surged by approximately 25% in premarket trading, reflecting investor optimism about the drug's potential.

Future Prospects and Ongoing Development

While the STELLAR-303 results mark a significant milestone for zanzalintinib, Exelixis is also pursuing additional indications to fully realize the drug's potential. The company is currently conducting studies in renal cell carcinoma (RCC) and head and neck cancer, with important milestones expected in the latter half of this year.

These upcoming results, including a Phase III topline readout for RCC and a go/no-go decision for zanzalintinib as a frontline therapy in head and neck cancer, will be crucial in determining the full scope of the drug's applications and its ability to meet Exelixis' ambitious sales projections.

As zanzalintinib progresses through clinical development, it may face competition from other established and emerging treatments in the colorectal cancer space, including Amgen's Lumakras, Taiho Oncology's Lonsurf, and Takeda's Fruzaqla. However, the positive STELLAR-303 results position zanzalintinib as a strong contender in this competitive landscape.