Exelixis unveils positive results from phase 2 trial of cabozantinib in previously untreated advanced RCC

The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for cabozantinib compared with sunitinib in patients with advanced intermediate- or poor-risk RCC.

The safety data in the cabozantinib-treated arm of the study were consistent with those observed in previous studies in patients with advanced RCC. CABOSUN is being conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP). The final results from CABOSUN will be submitted for presentation at a future medical conference.

"The positive outcome of CABOSUN is extremely exciting, as it marks the very first time that a therapy has shown a progression-free survival benefit over standard of care first-line treatment sunitinib for patients with previously untreated advanced renal cell carcinoma," said Toni K. Choueiri, M.D., Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and chair of the CABOSUN study.

"Based on these findings, cabozantinib may have the potential to become a new gold standard for previously untreated patients following their diagnosis with advanced kidney cancer."

"All of us at the Alliance for Clinical Trials in Oncology are very gratified to have successfully demonstrated the potential of first-line cabozantinib to benefit patients with renal cell carcinoma in the CABOSUN study. This trial exemplifies how NCI-sponsored studies can be efficient, accrue rapidly, and yield results highly relevant to the field," said Michael J. Morris, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary (GU) Committee.

Exelixis will share the results of CABOSUN with regulatory authorities to discuss potential next steps in the development and submission strategy for cabozantinib as a treatment of first-line advanced renal cell carcinoma. Exelixis is also working closely with clinical advisors on the development plan for cabozantinib in future clinical trials in other genitourinary malignancies.

"Demonstrating an improvement in progression-free survival with cabozantinib compared to sunitinib as a first-line treatment represents an important milestone for patients with previously untreated RCC," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis.

"We are thrilled to be a part of the many recent advances in the treatment of advanced kidney cancer and would like to thank the patients, physicians, nurses, caregivers, the Alliance cooperative group and NCI-CTEP who made this clinical trial possible. We look forward to pursuing next steps in the development of cabozantinib in the first-line treatment of patients with advanced RCC and other GU malignancies."

About the CABOSUN Study

CABOSUN is a randomized, open-label, active-controlled phase 2 trial that was designed to enroll 150 patients with advanced RCC determined to be intermediate- or poor-risk by the International Metastatic RCC Database Consortium (IMDC) criteria.

Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The randomization was stratified by the IMDC risk strata (intermediate or poor risk) and presence of bone metastasis (yes, no). Enrollment was completed in March 2015.

The primary endpoint was PFS, defined as time from randomization to disease progression or death, whichever occurs first. Positive PFS results have formed the basis for previous regulatory approvals of treatments in the first-line setting, including sunitinib. Secondary endpoints included overall survival and objective response rate.

Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and had to be intermediate or poor risk, per the IMDC Criteria (Heng JCO 2009). Prior systemic treatment for RCC was not permitted. With 123 events (disease progression or death), the log-rank statistic has 85 percent power (with a one-sided type I error rate=0.12) to detect a hazard ratio of 0.67. Between July 9, 2013 and April 6, 2015, 157 patients were randomized: 79 patients on the cabozantinib arm and 78 patients on the sunitinib arm.