Exelixis Announces Positive Findings at ASCO GU for CABOMETYX® (cabozantinib) in Patients with Brain Metastases from Renal Cell Carcinoma

– Results of retrospective analysis demonstrate a 61% intracranial response rate in patients with progressing brain metastases –

– Data to be presented during the 2021 American Society of Clinical Oncology’s Genitourinary Cancers Symposium –

ALAMEDA, Calif.--(BUSINESS WIRE)-- Exelixis, Inc. (NASDAQ: EXEL) today announced results from a retrospective analysis evaluating CABOMETYX® (cabozantinib) activity in brain metastases in patients with renal cell carcinoma (RCC). The findings will be presented as part of the Poster Session: Renal Cell Cancer at the 2021 American Society of Clinical Oncology’s Genitourinary Cancers Symposium (ASCO GU), which is being held virtually, February 11-13, 2021. All posters will be available on demand beginning at 5:00 a.m. PT on Thursday, February 11.

In this retrospective analysis of medical records from patients with metastatic RCC with brain metastases, an intracranial response rate of 61% (95% CI: 39%-80%), including a complete response rate of 13%, was seen for patients with progressing intracranial metastases at baseline (Cohort 1; n=25) who were treated with CABOMETYX. Patients without progressing intracranial metastases (Cohort 2; n=44) had an intracranial response rate of 57% (95% CI: 41%-72%). The rate of brain disease progression at six months was 16% for patients with progressive brain disease at baseline and 9% for those without. Median overall survival was 14.7 months for Cohort 1 and 14.1. months for Cohort 2. The reported safety data are consistent with the known safety profile for CABOMETYX.

“With these exciting results, oral systemic cabozantinib is showing intriguing activity on brain metastases in renal cell carcinoma,” said Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. “The high intracranial response rates seen in this retrospective analysis suggest cabozantinib has the potential for helping patients with difficult-to-treat brain lesions from kidney cancer. We look forward to building on these encouraging findings through the ongoing phase 2 CABRAMET trial (NCT03967522) led by our French colleagues, which is prospectively evaluating cabozantinib in patients with brain metastases from renal cell carcinoma.”

“Brain metastases resulting from renal cell carcinoma are especially difficult to treat, as the blood-brain barrier poses a challenge for therapies to reach their targets,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “These encouraging results including a high intracranial response rate, suggest CABOMETYX may reduce the size of brain metastases, without neurological toxicity, and thereby may be of interest to physicians treating kidney cancer patients with brain metastases.”

About the Study

For this retrospective study, sponsored by the Dana-Farber Cancer Institute, consecutive medical records from patients with metastatic RCC with brain metastases who had been treated with cabozantinib monotherapy across 15 institutions in the United States (ten centers), Belgium (three centers), Spain (one center) and France (one center) were reviewed.

Patients were divided into two cohorts based on the presence (n=25) or absence (n=44) of progressing intracranial metastases at start of CABOMETYX therapy. Most patients (87%) were International Metastatic RCC Database Consortium (IMDC) intermediate/poor risk, and 75% had been previously treated. Prior brain-directed therapy was received by 65% of patients with progressing brain metatstases and by 93% of those without. All patients were treated with CABOMETYX. Four patients were not included in the intracranial analysis due to brain lesion size under 5 mm.

About RCC

The American Cancer Society’s 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common form of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.1 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.3

About 70% of RCC cases are known as “clear cell” carcinomas, based on histology.4 The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About CABOMETYX® (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with HCC who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States 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 United States.

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 and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. 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 36% (17% 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.

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 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 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in