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Group to study immunotherapy-targeted therapy combination for metastatic colon cancer
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Researchers at University of Colorado Cancer Center and partnering institutions received a grant to study a novel combination therapy for patients with microsatellite-stable metastatic colon cancer.
Christopher Lieu, MD, CU Cancer Center’s deputy associate director for clinical research, and colleagues will investigate the VEGF inhibitor bevacizumab (Avastin, Genentech) and MEK inhibitor binimetinib (Mektovi, Array BioPharma), along with PD-1 inhibitor pembrolizumab (Keytruda, Merck), in this difficult-to-treat patient population. The researchers believe that shutting down all three pathways impacted by these drugs will be an effective attack on microsatellite-stable (MSS) disease.
Study protocols also will allow for investigation of biomarkers in tumor tissue samples, which could offer insight into the success or failure of the combination for certain patients.
HemOnc Today spoke with Lieu about the challenges associated with developing an effective treatment for this patient population and which patients may be most likely to respond to this combination.
Question: Why did you choose this particular combination?
Answer: We had a trial of a MEK inhibitor in combination with another drug at University of Colorado and other centers across the country. We were able to get biopsies before and after treatment with the MEK inhibitor. We saw that the T cells seemed to increase around the cancer and infiltrate the cancer. With MSS colorectal cancer, the problem is there are no T cells around the cancer to activate with pembrolizumab. The idea was to get the T cells there with the binimetinib and bevacizumab and then turn them on with the immunotherapy.
Q: How many patients do you hope to accrue?
A: We’re doing a 10-patient safety run-in just to ensure that the combination is safe, which we believe it will be. The entire study will enroll 40 patients.
Q: What are your expectations in terms of results?
A: We are obviously excited about the trial, but we don’t have any grand dream that this is going to end up with a gigantically high response rate. But the reasons we are doing the trial are twofold. No. 1, obviously, is that we are hoping the combination of all three drugs is more effective than any of the drugs alone. We may find a subset of patients that respond very well to this combination. The second reason is that, even if the combination doesn’t end up working, we are obtaining blood and tumor samples that will help us determine why the combination is effective for certain patients but not for others. The idea is that if we have tumor samples that we can study before and after treatment, we may be able to better predict who will respond well. But almost more importantly, we may be able to figure out some of the resistance mechanisms that tumor employs that made the combination ineffective.
Q: Do you have any predictions about which patients will respond and which will not?
A: If we see a big immune response in the patients who receive the targeted therapy prior to starting the immunotherapy —meaning T cells getting to the tumor — those patients are likely to respond best. If the targeted therapy really does have the effect of turning the immune system against the cancer, then you turn it on with the immune therapy, it follows that those patients will be the best responders.
Q: Can you offer a few general comments on this patient population?
A: Immunotherapy has worked for a very small subset of patients — about 4% — with microsatellite instability-high metastatic colorectal cancer. The other 95% or 96% of patients need better treatment options. What we’re trying to do is come up with a better strategy so that the majority of patients with metastatic colorectal cancer therapy have an immunotherapy option.
Q: What is the timeline for the trial?
A: I suspect that it will be open for about a year and then it will be done. – by Rob Volansky
For more information:
Christopher Lieu, MD, can be reached at UCHealth Anschutz Cancer Pavilion-Anschutz Medical Campus, 1665 Aurora Court, Aurora, CO 80045; email: christopher.lieu@ucdenver.edu.
Disclosure: Lieu reports no relevant financial disclosures.