Exelixis Enters into Collaboration with Merck to Evaluate Zanzalintinib for Cancer Treatment
Tuesday, October 15, 2024
Exelixis and Merck have entered a clinical development partnership to investigate the combination of Exelixis’ investigational tyrosine kinase inhibitor (TKI), zanzalintinib, with Merck’s therapies.
Head and neck cancer includes a range of tumors that develop around the throat, larynx, nose, sinuses, and mouth. The majority of these cancers are squamous cell carcinomas, which form in the flat cells lining the head and neck structures.
Tobacco and alcohol use, as well as HPV infection, are significant risk factors for these cancers. Globally, over 891,500 new cases and 458,100 deaths were recorded in 2022. In the U.S., it is expected that over 58,450 new cases will be diagnosed in 2024, with more than 12,230 deaths.
Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for around 90% of cases. RCC is more prevalent in men than in women, and most cases are found incidentally during imaging for unrelated abdominal issues.
Recurrence rates are high, with up to 40% of newly diagnosed patients experiencing recurrence within five years of surgery. In 2024, the U.S. is projected to see 81,600 new cases of kidney cancer and 14,400 deaths. Globally, there were approximately 434,840 new cases and 155,953 deaths from kidney cancer in 2022.
Zanzalintinib is a TKI that targets multiple pathways involved in cancer resistance to various therapies, including immune checkpoint inhibitors. Early data from the phase 1b STELLAR-001 trial demonstrated encouraging results in patients with previously treated clear cell RCC.
KEYTRUDA® is an anti-PD-1 therapy designed to enhance the body’s immune response against cancer cells. By blocking the interaction between PD-1 and its ligands (PD-L1 and PD-L2), KEYTRUDA activates T cells that target both tumor cells and healthy tissue. Merck has an extensive immuno-oncology program, with more than 1,600 ongoing trials exploring the use of KEYTRUDA in various cancers. These studies aim to identify biomarkers that can predict patient outcomes.
This collaboration will focus on two cancer types: head and neck squamous cell carcinoma (HNSCC) and renal cell carcinoma (RCC).
In a phase 3 trial, the combination of zanzalintinib with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) will be evaluated for the treatment of patients with HNSCC. Additionally, zanzalintinib will be tested with WELIREG® (belzutifan), Merck’s oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, in phase 1/2 and phase 3 trials for the treatment of RCC.
Merck will provide KEYTRUDA for the phase 3 STELLAR-305 trial, which focuses on patients with PD-L1 positive recurrent or metastatic HNSCC who have not received prior treatment.
The company will also sponsor a phase 1/2 trial and two phase 3 trials in RCC, with one of the phase 3 studies fully funded by Merck.
Exelixis will co-fund the other trials and supply both zanzalintinib and cabozantinib. Despite this collaboration, Exelixis retains global commercial rights for zanzalintinib.
Source: exelixis.com
