Exelixis, Inc. (NASDAQ:EXEL) today announced it has initiated METEOR, a phase 3 pivotal trial comparing cabozantinib to everolimus in patients with metastatic renal cell carcinoma (mRCC) who have experienced disease progression following treatment with at least one prior VEGFR tyrosine kinase inhibitor (TKI). The primary endpoint for the trial is progression-free survival.
“Initiation of this phase 3 pivotal trial in mRCC is an important component of our development strategy to expand the cabozantinib franchise by exploring additional indications with the goal of providing patients with new treatment options”
"RCC patients who progressed after or who are refractory to initial treatment with VEGFR-TKI therapy have limited treatment options," said METEOR Principal Investigator Toni K. Choueiri, M.D., Director of the Kidney Cancer Center at the Dana-Farber Cancer Institute and an Associate Professor of Medicine at Harvard Medical School. "The cabozantinib data to date in RCC patients previously treated with VEGFR-TKIs showed encouraging anti-tumor activity, and provide a sound rationale for the design of the METEOR phase 3 study comparing cabozantinib to everolimus in this indication."
METEOR is an open-label trial of cabozantinib in patients with mRCC that is being conducted at up to 200 sites in up to 26 countries. The trial is expected to enroll 650 patients with clear cell RCC who have received and progressed on at least one VEGFR-TKI. Patient enrollment will be weighted toward Western Europe, North America, and Australia, and patients will be stratified based on the number of prior VEGFR-TKI therapies received and commonly applied RCC risk criteria developed by Motzer et al. Patients will be randomized 1:1 to receive 60 mg of cabozantinib daily or 10 mg of everolimus daily. No cross-over is allowed between the study arms.
The primary endpoint is progression-free survival (PFS) and the secondary endpoint is overall survival (OS). Exploratory endpoints include patient-reported outcomes, biomarkers, safety, and pharmacokinetics. PFS is an established acceptable endpoint for RCC clinical trials and has been used to support approval of sorafenib, sunitinib, everolimus, axitinib, and pazopanib in this indication.
Based on available clinical trial data, the primary endpoint assumes a median PFS of 5 months for the everolimus arm and 7.5 months for cabozantinib arm. This provides for a hazard ratio (HR) of 0.67 and 90% power and requires 259 PFS events among the first 375 patients randomized. The secondary endpoint assumes a median OS of 15 months for the everolimus arm and 20 months for the cabozantinib arm. This provides for a HR of 0.75 and 80% power and requires 413 events.
"Initiation of this phase 3 pivotal trial in mRCC is an important component of our development strategy to expand the cabozantinib franchise by exploring additional indications with the goal of providing patients with new treatment options," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Our pre-phase 3 meetings with regulatory authorities in the U.S. and Europe, as well as feedback gathered from expert oncologists around the globe, have helped us design a trial that is intended to provide for a robust examination of cabozantinib's clinical potential as a treatment for mRCC. We also remain on track to begin a phase 3 pivotal trial of cabozantinib in patients with metastatic hepatocellular carcinoma in the third quarter of this year."