– Results demonstrated an objective response rate of 54% and an overall clinical benefit rate of 91% –
ALAMEDA, Calif.--(BUSINESS WIRE)-- Exelixis, Inc. (Nasdaq: EXEL) today announced results from a phase 2, investigator-sponsored trial of cabozantinib (CABOMETYX®) in combination with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The data will be presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting during Oral Abstract Session: Head and Neck Cancer on Friday, June 3 beginning at 2:45 p.m. CT.
The trial met its primary endpoint of objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at 54%. The overall clinical benefit rate was 91%. At a median follow-up of 10.6 months, the one-year progression-free survival rate was 54.0% (95% confidence interval [CI]: 31.5-72.0%), and median progression-free survival was 14.6 months. The one-year overall survival (OS) rate was 68.4% (95% CI: 45.1-83.5%; median OS: 22.3 months). For the 17 patients with a PD-L1 combined positive score (CPS) under 20, the one-year OS rate was 54.9% (95% CI: 24.5-77.5%; median OS: 14.6 months). For the 17 patients with a CPS score of 20 or more, the one-year OS rate was 83.6% (95% CI: 48.0-95.7%; median OS: 32.9 months).
“Metastatic head and neck cancer is a challenging disease to treat, particularly following disease progression after definitive therapy, meaning patients need additional options beyond radiation and chemotherapy,” said Nabil F. Saba, M.D., Professor and Vice Chair, Hematology and Medical Oncology, The Lynne and Howard Halpern Chair in Head and Neck Cancer Research, Co-Director of Head and Neck Cancer Multidisciplinary Program, Winship Cancer Institute, Emory University, and primary investigator of the investigator-sponsored trial. “These results showing promising clinical activity of cabozantinib in combination with pembrolizumab are encouraging to these patients who face poor outcomes.”
In this phase 2 trial, eligible patients had recurrent or metastatic HNSCC that was deemed inoperable, with measurable disease per RECIST version 1.1, a life expectancy of at least 3 months and an Eastern Cooperative Group Performance Status of 0 or 1. Of the 36 evaluable patients, 61% had cancer in the oropharynx, 16% in the nasopharynx, 11% in the larynx, 6% in the hypopharynx and 6% in the oral cavity. Eighty-nine percent of patients had received prior radiation therapy and all had received prior chemotherapy.
The most frequent adverse events (AEs) were fatigue (44.4%), diarrhea (33.3%), hypothyroidism (33.3%), constipation (30.6%), dry mouth (27.8%), anorexia (25.0%), headache (25.0%), hypertension (25.0%), hyponatremia (25.0%) and oral mucositis (25.0%). Grade 3/4 treatment-related AEs were aspartate aminotransferase (AST) increase (8.3%), hyponatremia (8.3%), gamma-glutamyl transferase increase (5.6%), lipase increase (5.6%), oral mucositis (5.6%), alanine transaminase/AST increase (2.8%), bilirubin increase (2.8%) and hypertension (2.8%). Dose reductions occurred in 47.2% of patients, and AEs leading to discontinuation occurred in 25.0% of patients.
“Treatment options for patients with metastatic head and neck squamous cell carcinoma are limited, leaving a critical unmet need for this community,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “These data support the further development of a combination regimen of cabozantinib and an immune checkpoint inhibitor in patients with metastatic head and neck carcinoma and we are pleased to share these data at ASCO. Through our research, including our investigator-sponsored trials program, we continue to advance toward our goal of bringing new treatment options to people with difficult-to-treat cancers.”
About HNSCC
HNSCC comprises head and neck cancers that begin in the squamous cells that line the mucosal surfaces of the head and neck.1 Accounting for about 90% of all head and neck cancers, HNSCC is classified by its location: it can occur in the oral cavity, oropharynx, nasal cavity and paranasal sinuses, nasopharynx, larynx or hypopharynx.1,2 Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16.3 About 50,000 new cases of HNSCC are diagnosed in the U.S. every year.1 HNSCC is more common among men and people over the age of 50.4 Depending on the site of the cancer and level of metastases, the five-year survival rate for metastatic HNSCC ranges from 4-35%.5
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.
CABOMETYX is not indicated as a treatment for recurrent or metastatic HNSCC.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and 3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab. Withhold and resume at a reduced dose based on severity.
Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.
Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.
Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.
Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in