NEW YORK – Exelixis said Tuesday that it began a Phase III trial of its next-generation tyrosine kinase inhibitor, XL092, in patients with mismatch repair-proficient (pMMR), microsatellite stable metastatic (MSS) colorectal cancer.
The STELLAR-303 trial will compare the combination of XL092 with Roche's Tecentriq (atezolizumab) against Bayer's Stivarga (regorafenib) in about 600 patients with RAS wild-type or RAS-mutated tumors without high microsatellite instability or mismatch repair deficiency. Patients must have progressed or be intolerant to standard therapy to partake in the study.
The primary endpoint of the trial is overall survival, with progression-free survival, objective response rate, and duration of response as secondary endpoints. Researchers will also study the efficacy of the drug combination in people with RAS-mutated disease as an exploratory endpoint.
Alameda, California-based Exelixis decided to study XL092 in this setting based on the results from two trials involving its TKI Cabometyx (cabozantinib). At the American Society of Clinical Oncology's Gastrointestinal Cancers Symposium in January, researchers reported that in the Phase II CAMILLA trial, Cabometyx with AstraZeneca's Imfinzi (durvalumab) had promising efficacy and was well tolerated in heavily pretreated patients with pMMR/MSS colorectal cancer. The subgroup of patients with wild-type RAS tumors had increased overall survival, progression-free survival, and other indicators of improved response on therapy compared to the group overall.
At the same meeting, researchers shared data from a Phase Ib trial (COSMIC-021) of Cabometyx with Tecentriq in advanced solid tumors, which suggested that colorectal cancer patients with wild-type RAS tumors had increased progression-free survival and overall survival compared to patients with RAS mutations.
"There is a significant need for new treatment options for the majority of metastatic colorectal cancer patients who do not have microsatellite instability-high or mismatch-repair deficient disease and whose tumors do not respond to immunotherapy alone," Exelixis Chief Medical Officer Vicki Goodman said in a statement. "We look forward to learning more about how XL092 in combination with atezolizumab may benefit patients with metastatic colorectal cancer."