Exelixis, Inc. (NASDAQ:EXEL) today announced the initiation of two investigator-sponsored trials (ISTs) of cabozantinib, which simultaneously targets MET, VEGFR2 and RET. Naiyer Rizvi, M.D., a lung cancer specialist at Memorial Sloan Kettering Cancer Center (MSKCC), is conducting a phase 2 clinical trial of cabozantinib in non-small cell lung cancer (NSCLC) patients who have tested positive for gene fusions that activate RET. Anuj Mahindra, MBBS, member of the hematology staff at Massachusetts General Hospital (MGH), is conducting a pilot phase 1 clinical trial of cabozantinib in patients with relapsed or refractory multiple myeloma, a disease for which there is evidence of MET’s role in pathogenesis.
“Exelixis’ IST Program is a critical component of our strategy to evaluate cabozantinib in a broad array of indications while focusing our internal efforts and resources on medullary thyroid cancer and prostate cancer,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We are pleased to support leading oncologists such as Dr. Rizvi and Dr. Mahindra as they leverage cabozantinib’s target-inhibition profile to address specific cancer indications in which these targets are believed to play a key role. For example, in the case of NSCLC, mounting evidence suggests that the presence of the KIF5B/RET fusion may signify a new molecular subset of the disease. An IST with cabozantinib, a potent inhibitor of RET that has shown strong clinical activity in another RET-driven cancer, is a logical next step in advancing new approaches to treat the disease.”
The phase 2 NSCLC trial is designed to enroll 25 patients with KIF5B/RET or related variant RET fusions in their tumors. These patients will receive a daily 60 mg dose of cabozantinib administered orally. The primary endpoint of the trial is overall response rate. Secondary endpoints include progression-free survival, overall survival, and safety. Investigators will also seek to determine the frequency of KIF5B/RET and related variant RET fusions in patients whose tumors are negative for previously identified oncogenic activating mutations or translocations (including those involving EGFR, KRAS, and ALK).