Exelixis and Merck Partner to Test Zanzalintinib with KEYTRUDA in Head and Neck Cancer and WELIREG in Renal Cell Carcinoma

Exelixis, Inc. (Nasdaq: EXEL) and Merck (NYSE: MRK), known as MSD outside of the U.S. and Canada, have announced a collaboration to investigate the use of Exelixis' zanzalintinib in combination with Merck's KEYTRUDA® (pembrolizumab) and WELIREG® (belzutifan) in clinical trials targeting head and neck squamous cell carcinoma (HNSCC) and renal cell carcinoma (RCC).

The collaboration will focus on a phase 3 pivotal trial to evaluate the combination of zanzalintinib and KEYTRUDA for HNSCC patients and a series of trials combining zanzalintinib with WELIREG for RCC patients. Specifically, the trials will include one phase 1/2 trial and two phase 3 pivotal trials.

Amy Peterson, M.D., Executive Vice President at Exelixis, emphasized the potential of zanzalintinib in combination with immunotherapy or targeted therapy to benefit patients with HNSCC and RCC, conditions with significant unmet clinical needs. Peterson noted that both KEYTRUDA and WELIREG have already shown improved outcomes for some cancer patients.

Dr. Marjorie Green, Senior Vice President and Head of Oncology at Merck Research Laboratories, expressed enthusiasm for the partnership with Exelixis and the potential to enhance patient outcomes through new combination regimens.

Under the collaboration agreement, Merck will provide KEYTRUDA for the Exelixis-sponsored phase 3 STELLAR-305 trial in previously untreated, PD-L1 positive recurrent or metastatic HNSCC. Merck will also sponsor and fund a phase 1/2 trial and one of the phase 3 trials in RCC, while Exelixis will co-fund the other phase 3 trial and provide zanzalintinib and cabozantinib. Exelixis retains all global commercial and marketing rights for zanzalintinib.

Head and neck cancer encompasses a variety of tumors located in or around the throat, larynx, nose, sinuses, and mouth. These cancers often start in the squamous cells lining the surface of these areas. The major risk factors include tobacco, alcohol consumption, and HPV infection. In 2022, over 891,500 new cases and 458,100 deaths from head and neck cancer were reported globally. In the U.S., projections for 2024 estimate over 58,450 new cases and more than 12,230 deaths.

Renal cell carcinoma, the most common type of kidney cancer, accounts for about 90% of kidney cancer diagnoses and is more prevalent in men. RCC is often discovered incidentally during imaging for other conditions. The recurrence rate is high, with up to 40% of newly diagnosed patients experiencing recurrence within five years post-surgery. In 2024, it is estimated that there will be 81,600 new kidney cancer cases and approximately 14,400 deaths in the U.S. Globally, 2022 saw about 434,840 new cases and over 155,953 deaths.

Zanzalintinib, an investigational tyrosine kinase inhibitor, targets multiple cancer-related pathways that contribute to resistance against therapies, including immune checkpoint inhibitors. Preliminary results from the phase 1b STELLAR-001 trial indicated promising outcomes in patients with previously treated clear cell RCC.

KEYTRUDA, an anti-PD-1 therapy, enhances the immune system's ability to detect and combat tumor cells by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thus activating T lymphocytes. Merck's extensive immune-oncology research program involves over 1,600 trials exploring the efficacy of KEYTRUDA across numerous cancer types and treatment settings.