Exelixis' Zanzalintinib Shows Promise in Colorectal Cancer, Positioning as Potential "Franchise Molecule"

Exelixis has unveiled promising data for its oral tyrosine kinase inhibitor (TKI) zanzalintinib, demonstrating a significant reduction in death risk for colorectal cancer patients compared to Bayer's Stivarga. The results, presented at the European Society for Medical Oncology (ESMO) Congress in Berlin, mark a potential breakthrough in the treatment of non-microsatellite instability-high metastatic colorectal cancer.

Zanzalintinib Outperforms Stivarga in Phase 3 Trial

In a phase 3 study involving 901 patients, the combination of zanzalintinib and Roche's checkpoint inhibitor Tecentriq showed a 20% reduced risk of death compared to Stivarga. The median overall survival (OS) at an 18-month follow-up was 10.9 months for the zanzalintinib-Tecentriq combination, surpassing the 9.4 months observed in the Stivarga-Tecentriq arm.

Dana Aftab, Ph.D., Executive Vice President of Research and Development at Exelixis, hailed the results as "an absolute win," noting that this marks the first time a TKI has demonstrated improvement with an immune checkpoint inhibitor in this specific patient population.

Safety Profile and Future Prospects

While the efficacy data is encouraging, the study also revealed that 59% of patients receiving the zanzalintinib combination experienced grade 3 or 4 treatment-related adverse events, compared to 37% in the Stivarga regimen. Aftab commented that this safety profile aligns with expectations for TKI-immune checkpoint inhibitor combination treatments.

Exelixis is positioning zanzalintinib as a successor to its flagship oncology medicine Cabometyx (cabozantinib). The company believes zanzalintinib has the potential to become a "franchise molecule" for gastrointestinal cancers, with projected revenues reaching $5 billion by 2033.

Regulatory Plans and Expansion

Exelixis is preparing to submit an approval application to the FDA for zanzalintinib in colorectal cancer this year. The company is also evaluating the drug in a phase 3 study for non-clear cell renal cell carcinoma, signaling its intent to expand the drug's indications.

"Just like cabozantinib, which we built into a very large franchise, we have huge plans for zanza[lintinib]," Aftab stated. "This is just the start."

As Exelixis continues to develop zanzalintinib, the pharmaceutical industry watches closely to see if this potential "franchise molecule" will indeed transform the landscape of cancer treatment, particularly in gastrointestinal oncology.