J. Randolph Hecht, MD from UCLA Health is conducting a phase 3 clinical trial called STELLAR-303 to evaluate the efficacy and safety of a novel multi-kinase inhibitor (MKI) called XL092 in combination with atezolizumab, an immune checkpoint inhibitor (ICI), compared to regorafenib in patients with previously treated metastatic colorectal cancer (mCRC).
The trial aims to address the limited treatment options available for patients who have progressed after front-line chemotherapy.
The prognosis for patients with mCRC is generally poor, with a 5-year survival rate of only 14%.
While regorafenib and trifluridine-tipiracil are approved for third-line or later treatment, the survival benefit is limited. Immune checkpoint inhibitor therapy is approved for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC, but this phenotype is only present in about 5% of patients.
Previous phase 1/2 trials have shown promising clinical activity when ICIs are combined with VEGFR2 multi-kinase inhibitors (MKIs) in mCRC.
For example, atezolizumab and durvalumab in combination with the MKI cabozantinib have shown encouraging results, particularly in patients with RAS wild-type disease.
XL092 is a novel MKI that targets MET, VEGFR2, and TAM kinases AXL and MER. Its relatively short half-life of approximately 21 hours allows for once-daily dosing and dose adjustments to manage tolerability.
STELLAR-303 is a global, open-label, randomized phase 3 study that plans to enroll 600 patients with previously treated RAS wild-type or mutant mCRC.
Eligible patients must have measurable disease, no MSI-H or dMMR status, and an ECOG performance status of 0-1. RAS and MSI/dMMR status will be determined through tissue-based analysis.
Participants will be randomly assigned to receive either XL092 100 mg orally once daily plus atezolizumab 1200 mg intravenously every three weeks, or regorafenib 160 mg orally once daily for 21 days in a 28-day cycle.
The study will assess the primary endpoint of overall survival in the RAS wild-type population, as well as secondary endpoints such as progression-free survival, objective response rate, and duration of response according to RECIST v1.1.
In addition to efficacy and safety evaluations, the trial will also examine quality of life, changes in biomarkers, pharmacokinetics, immunogenicity of atezolizumab, and healthcare utilization.
Enrollment for the STELLAR-303 trial is currently ongoing, and the clinical trial information can be found under the identifier NCT05425940.
This phase 3 study aims to provide valuable insights into the potential benefits of combining XL092 with atezolizumab for the treatment of previously treated RAS wild-type or mutant mCRC, addressing the need for more effective therapies in this patient population.
