Exelixis Presents Final Overall Survival Results from Phase 3 CONTACT-02 Pivotal Study Evaluating Cabozantinib in Combination with an Immune Checkpoint Inhibitor in Metastatic Castration-Resistant Prostate Cancer at ESMO 2024

ALAMEDA, Calif.--(BUSINESS WIRE)-- Exelixis, Inc. (Nasdaq: EXEL) today announced detailed final overall survival (OS) results from CONTACT-02, a phase 3 pivotal study evaluating cabozantinib (CABOMETYX®) in combination with atezolizumab (Tecentriq®) compared with a second novel hormonal therapy (NHT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and measurable extra-pelvic soft tissue disease who have progressed on one prior NHT. These data are being presented today at the 2024 European Society for Medical Oncology Congress (ESMO 2024) during the Proffered Paper Session: GU Tumours, Prostate at 2:45 p.m. CEST.

“Despite recent advancements, outcomes remain poor for patients with metastatic castration-resistant prostate cancer whose disease progresses after novel hormonal therapy – particularly those with liver metastases,” said Neeraj Agarwal, M.D., FASCO, Senior Director for Clinical Research at Huntsman Cancer Institute at the University of Utah and the global lead investigator of the trial. “I believe there is a critical need for novel agents with a new mechanism of action that are broadly accessible to patients and can delay disease progression. The positive results from CONTACT-02, especially in the subset of patients with liver metastasis, reinforce the therapeutic potential of cabozantinib in combination with atezolizumab for these patients.”

The two primary endpoints for CONTACT-02 were progression-free survival (PFS) and OS. At a median follow-up of 24.0 months, the final analysis of OS showed a numerical but not statistically significant improvement favoring cabozantinib in combination with atezolizumab (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296). An improvement in OS was observed in multiple clinical subgroups, notably in patients with bone or liver metastases, with the latter category representing a population whose disease may be evolving away from androgen receptor signaling. Additional OS efficacy findings are included in Table 1 below.

“Within the current treatment landscape, there is a growing population of patients with metastatic castration-resistant prostate cancer with extra-pelvic soft tissue metastases whose disease has progressed after novel hormonal therapy, leaving a high unmet need for effective, widely available treatments for these patients,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “Collectively, the results from the CONTACT-02 trial suggest that there are patients who could benefit from cabozantinib in combination with atezolizumab and that this regimen could be a valuable addition to the treatment landscape for patients with advanced prostate cancer.”

Treatment-related grade 3-4 adverse events (AEs) occurred in 40% of patients receiving cabozantinib in combination with atezolizumab and 8% of those receiving NHT. Treatment-related AEs leading to discontinuation of all treatment components were similar (5% for cabozantinib in combination with atezolizumab and 2% of those receiving NHT). The time to clinically meaningful deterioration in quality of life was similar between arms, and the combination of cabozantinib and atezolizumab did not impair quality of life relative to generally well-tolerated NHT.

As previously announced, CONTACT-02 met one of its two primary endpoints, demonstrating a statistically significant benefit in PFS in the predefined PFS ITT population (i.e., the first 400 randomized patients). Detailed results were presented at the American Society of Clinical Oncology 2024 Genitourinary Cancers Symposium in January 2024. Exelixis intends to submit a supplemental New Drug Application with the U.S. Food and Drug Administration for cabozantinib in combination with atezolizumab for mCRPC later this year.

About CONTACT-02 CONTACT-02 is a global, multicenter, randomized, phase 3, open-label study that randomized 575 patients 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of a second NHT (either abiraterone and prednisone or enzalutamide). The two primary endpoints of the trial are PFS and OS. The study included patients with mCRPC who have measurable extra-pelvic soft tissue metastasis and who have progressed on one prior NHT. The secondary endpoint is objective response rate per blinded independent radiology committee. The trial is sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda Pharmaceutical Company Limited (Takeda). Takeda is conducting the trial in Japan. More information about CONTACT-02 is available at ClinicalTrials.gov.

About CRPC According to the American Cancer Society, approximately 299,000 new cases of prostate cancer will be diagnosed in the U.S., and over 35,000 people will die from the disease in 2024.1 Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies—a common treatment for prostate cancer—is known as mCRPC.2 Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years.3,4

About CABOMETYX® (cabozantinib) In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; 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 VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the European Union. 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 CRPC.

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