ASCO 2023 | STELLAR-303: XL092 with atezolizumab compared to regorafenib in patients with mCRC
J. Randolph Hecht, MD, UCLA Santa Monica Medical Center, Santa Monica, CA, comments on the Phase III STELLAR-303 study (NCT05425940) which aims to evaluate the efficacy and safety of the tyrosine kinase inhibitor (TKI), XL092, in combination with atezolizumab versus regorafenib in patients with microsatellite stable or microsatellite instability-low metastatic colorectal cancer (mCRC). The mechanism of action of XL092 involves targeting of MET, VEGFR2, and the TAM kinases AXL and MER. The primary endpoint includes duration of overall survival (OS), progression-free survival (PFS), objective response rate (RR), duration of response, and change in tumor markers in the patients with wildtype RAS. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Annual Congress in Chicago, IL.
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Transcript (edited for clarity)
We have an incredible unmet need in the salvage setting for colorectal cancer patients while people get benefit with cytotoxic chemotherapy. Median survival has really stagnated at about three years and the current drugs that we have such as regorafenib, are TAS-102, which are approved have modest benefit...
We have an incredible unmet need in the salvage setting for colorectal cancer patients while people get benefit with cytotoxic chemotherapy. Median survival has really stagnated at about three years and the current drugs that we have such as regorafenib, are TAS-102, which are approved have modest benefit. Immunotherapies in the 97% of patients who have proficient DNA mismatch repair have not been particularly helpful. So there is a large, large effort to try to bring the immunotherapy revolution to colorectal rectal, colorectal cancer, particularly in the metastatic setting, particularly in the 97%.
So the trial I’m going to talk about today is the STELLAR303 trial. This is a large international randomized trial with a drug that used to be called XL 92, which is now called zanzalintinib. And it’s a multi-targeted tyrosine kinase inhibitor that inhibits a number of immunosuppressive pathways in combination with the PD-L1 antibody atezolizumab.
This is a large randomized trial against standard of care regorafenib. There have been a number of smaller trials which have shown activity of the combination of either zanza or the very similar drug cabozantinib together with checkpoint inhibitors in metastatic colorectal cancer. This is building on that.
In addition, there have been trials with a drug called regorafenib, which is also a tyrosine kinase inhibitor that may not hit the same immunosuppressive pathways. But even that in combination with an immune checkpoint inhibitor showed some activity. So this large randomized trial we’re looking specifically at patients who are RAS wild type though, there is a separate cohort for patients who have a RA mutation. It’s currently open, it’s international. It is also opened in the United States. And we’re very hopeful that this will kind of break the logjam and help our patients who really, truly have an unmet need.
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