Focusing on novel immune checkpoint inhibitors, Robert L. Coleman, MD, FACOG, FACS, breaks down preclinical and clinical data that support use of balstilimab in patients with advanced cervical cancer.
Robert L. Coleman, MD, FACOG, FACS: There has been a lot of excitement about the use of immune checkpoint inhibitors in solid tumor therapy. This extends to different tumor types, most of which we’ve seen a benefit to, but not all. One of the diseases where we have seen activity has been cervix cancer. As a viral-induced disease, we see local environment of tumor neoantigens, which would make it a tumor type that would have high rationale for an immune checkpoint inhibitor to possibly work.
We’ve tested this. This was initially tested in the lab to identify that cancer cells and immune effector cells are both present in the tumor microenvironment expressing the target that these drugs (such as balstilimab) are going after. (The purpose is to focus on) the antigen for this immune escape mechanism that’s present in the tumor microenvironment. This exists both on cells and in the immune effector cells. There’s a lot of rationale to support the use of immune checkpoint inhibitors to block this suppressive interaction between the immune response to treatment and the presence of the tumor. There’s been a wealth of preclinical data to support this mechanism of action. Fortunately, we now have clinical proof that such a relationship is important in the natural history of tumor biology.
In our experience with looking at the clinical efficacy of these immune checkpoint inhibitors in tumors that don’t express the ligand for PD-L1, we have seen a few objective responses. We have also modeled this in the lab and found that some patients’ cells are still responsive to this type of targeting. There are a couple of ways you could look at it. One is to say that there’s this particular agent that’s very robust in its activity and can apply to tumors that are both PD-L1 positive and negative, or you could say that PD-L1 positive and negative status is maybe a more imperfect biomarker for efficacy to immune checkpoint inhibitors. We know that this is the case for other tumor types that aren’t driven by tumor mutational burden. Ovarian cancer is probably one of the best examples of this, where we see PD-L1 expression, but we don’t see activity against immune checkpoint inhibitors. We know that the biomarker itself is helpful in certain tumor types, but it has its imperfections and doesn’t necessarily directly correlate to efficacy.
We’re excited because, at least in the preclinical work that had been reported recently with balstilimab against another immune checkpoint inhibitor, nivolumab, we saw a differential between those 2 compounds and PD-L1 status. The jury is still out as to whether we can make a broad statement that these drugs have activity in both settings.
Balstilimab, an immune checkpoint inhibitor, has been studied in probably one of the largest studies that has been conducted in patients with cervix cancer to look for clinical efficacy, proof of mechanism, and proof of concept. The trial was recently reported by Dave O’Malley [,MD, director, Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center]. We have seen preclinical efficacy for this compound, and putting this in front of patients with metastatic and recurrent, previously treated cervix cancer demonstrated that there was what we would consider important clinical efficacy. When we think about this from the standpoint of what we’d consider highly effective therapy—we use objective response for that—we find that we could almost be a little disappointed that these drugs hadn’t worked to a higher degree to produce objective response. But we have seen that although many patients may not respond per criteria, like the RECIST [Response Evaluation Criteria in Solid Tumors] criteria, they actually have a prolongation of time until progression. Those who responded to therapy had a quite impressive duration of response. These factors are clinically meaningful, probably more so than the objective response. To see a median duration response not even reached, we’re very excited that this has important clinical ramifications for our patients who have recurrent cervix cancer.
Transcript edited for clarity.