Interview: Defactinib Plus Pembrolizumab and Gemcitabine Effective in Pancreatic Cancer Patients

A study presented as part of the American Association for Cancer Research virtual meeting found promising results for defactinib combined with pembrolizumab and gemcitabine in patients with advanced pancreatic cancer.

DocWire News interviewed Andrea Wang-Gillam, MD, PhD, lead study author and presenter, about the research and what the future holds for further exploration of this area.

About Dr. Wang-Gillam: Dr. Andrea Wang-Gillam is a medical oncologist and physician-scientist with a focus on clinical and translational research in pancreatic cancer. Her research passion is fueled by the fact that pancreatic cancer patients have a short life expectancy due to lack of early detection and effective treatments. A specific research interest is to translate preclinical discoveries into clinical settings by designing and conducting hypothesis-driven trials. Dr. Wang-Gillam is the principal investigator on multiple clinical trials in pancreatic cancers.

DocWire News: What prompted you to undertake your study?

Dr. Wang-Gillam: I’m a GI oncologist with a focus in pancreatic cancer, as you know. A patient with pancreatic cancer has really poor prognosis. We’re really interest in developing novel therapeutics for patients with pancreatic cancer. This study has a strong preclinical rationale. The study as done in a laboratory showed the cohesion kinase pathways hyperactive in pancreatic cancer, also associated with a poor clinical outcome. The study done in animal models in pancreatic cancer showed if you block the cohesion kinase pathway along with a checkpoint inhibitor, anti-chemotherapy, that yields the best result in terms of the late tumor growth in those animal models, as well as improved survival for the mice bearing pancreatic cancer. We feel the strong rationales that really support this current study.

DocWire News: What are the key points or takeaways of the study?

Dr. Wang-Gillam: This is the phase one study, trying to test at first the optimal dose of the three drugs’ combination. The key takeaway, one, is that we know what is the optimal dose for the three drugs combination. We know what side effects it’s associated with. We know the optimal dose.

Then the second point is we look at two specific studies in patients with pancreatic cancer. One is in the maintenance study, when a patient received a frontline therapy consisting of Nab-paclitaxel and gemcitabine after four months or so, if they have a stable disease. At [that] time, they are tired of chemotherapy, especially the toxicity associated with those two agents, and we push them to them a triple drug, which actually is much better tolerated. We only have one chemotherapy in that maintenance setting and those people stay on treatment about every 4.6 months or so. We’ve recorded a median time on treatment of 4.6 months, which is quite encouraging for this patient population.

Patients who progressed on the frontline treatment for metastatic disease can enroll in the study either as a second line or third line or beyond. Basically we call them the fracturing cohort. We analyze the sick patients. Some are from dose escalation, some from this particular extension cohort. Of the 16 patients, we have the median progression rate of survival about 3.7 months, and overall survival, 7.8 months. This is actually encouraging efficacy also for a metastatic pancreatic cancer progressed beyond the front line therapy. I think the bottom line is the regimen is well-tolerated and we’re encouraging clinical activity per our clinical study.

DocWire News: Did any of the findings surprise you?

Dr. Wang-Gillam: One is I think how well patients tolerate the triple drug regimen—I think I was a little surprised how well tolerated. I think the second is some of the patients who stayed on the therapy more than a year. And there are some patients responding extremely well. For instance, we have two patients who had a partial response in this study. They actually do not have the microsatellite instability, they have what we call MS Stable Disease, and that’s surprising. They had a PR partial response and had a durable response for awhile. So those are some almost extreme responders that surprised me as well.

DocWire News: What were some of the limitations of the study?

Dr. Wang-Gillam: It’s a very small, phase one study. We need to expand to a larger study to appropriately evaluate the efficacy.

DocWire News: Are there any future research plans for this area?

Dr. Wang-Gillam: There have been discussions on how to expand it beyond what we have for a larger study, and in what setting. Those are being actively discussed.

DocWire News: Do you have any closing comments for our readers?

Dr. Wang-Gillam: One important thing is that we make very small increments in terms of improving survivals with a chemotherapy patient with pancreatic cancer. I feel encouraged that patients with pancreatic cancer participate in clinical trials because that is the only way we can move the field forward to bring the novel therapy into these settings. I think clinical trials definitely should be encouraged for patients with pancreatic cancer.