Exelixis and Merck have entered into a clinical development collaboration to evaluate novel combinations featuring Exelixis' investigational tyrosine kinase inhibitor (TKI), zanzalintinib, in head and neck squamous cell carcinoma (HNSCC) and renal cell carcinoma (RCC). The collaboration aims to address unmet clinical needs in these cancers by combining zanzalintinib with Merck's Keytruda (pembrolizumab) and Welireg (belzutifan).
Collaboration Details
Under the terms of the agreement, the collaboration will focus on the following:
- HNSCC: A Phase III pivotal trial (STELLAR-305) will evaluate the combination of zanzalintinib and Keytruda in previously untreated PD-L1 positive recurrent or metastatic HNSCC.
- RCC: Zanzalintinib will be combined with Welireg in a Phase I/II trial and two Phase III trials for RCC.
Merck will supply Keytruda for the STELLAR-305 trial. Funding for the trials will be shared, with Merck funding one of the Phase III RCC studies and Exelixis co-funding the Phase I/II study and the other Phase III study. Exelixis will retain global commercial and marketing rights to zanzalintinib.
Rationale for the Collaboration
Amy Peterson, MD, EVP, product development & medical affairs, chief medical officer, Exelixis, stated, "This collaboration underscores our belief in zanzalintinib’s potential to drive patient benefit in combination with immunotherapy or targeted therapy in HNSCC and RCC indications that have unmet clinical need."
Keytruda, an anti-PD-1 therapy, enhances the body's immune system to detect and fight tumor cells and is currently being evaluated in over 1600 trials across various cancers. Welireg, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, is approved for certain VHL disease-associated tumors and advanced RCC, demonstrating efficacy in controlling tumor growth by inhibiting HIF-2α.
Marjorie Green, SVP, head of oncology, global clinical development, Merck Research Laboratories, added, "Merck remains committed to building upon the progress made to-date by strategically evaluating the potential of new combination regimens to improve outcomes for more patients."
Disease Burden and Current Treatment Landscape
Globally, approximately 900,000 people are affected by HNSCC, with around 400,000 deaths annually. In the United States, there are about 71,100 cases. Renal cell carcinoma also represents a significant global health burden with high incidence rates and associated mortality.
The current treatment landscape for HNSCC and RCC includes immunotherapy, targeted therapies, and chemotherapy. However, there remains a significant unmet need for more effective treatments, particularly for patients who do not respond to existing therapies or who experience disease progression.
About Zanzalintinib
Zanzalintinib is an investigational tyrosine kinase inhibitor (TKI) that targets multiple cancer-related pathways. It has shown encouraging results in previously treated clear cell RCC, suggesting potential benefits in combination with immunotherapy or targeted therapy.
