Authors: James Gulley
In this interview with James Gulley, we explore the results of the Phase I trial for M7824. The results provided preliminary evidence that combining the anti-PD-L1 mechanism with a transforming growth factor-β (TGF-β) trap in one molecule may generate anti-tumor activity in a heavily pre-treated patient population who have previously failed therapy with anti-PD-L1/PD-1 checkpoint inhibitors. Patients with anti-PD-L1/PD-1 refractory or resistant advanced NSCLC have severely limited treatment options available to them and the preliminary results of this trial are a promising first step towards identifying treatment modalities that could potentially benefit these patients with significant unmet needs.
Could you tell us about the current status of anti–PD-1/PD-L1 therapy for NSCLC?
Nivolumab and pembrolizumab are approved for NSCLC; nivolumab for second line and pembrolizumab for first line, if PDL1 expression is seen in at least 50% of the tumor cells. Pembrolizumab is also used with docetaxel in first line regardless of PDL1 staining. There is also very interesting data with durvalumab suggesting substantial improvement in progression-free survival (PFS) (hazard ratio approximately 0.5) in patients with stage III lung cancer treated with durvalumab vs. placebo. However, there remains a great need for therapies in patients who progress following PD1/PDL1 targeted agents.
Would you like to find out more about pembrolizumab for NSCLC?
Check out this peer-reviewed Drug Evaluation from Immunotherapy.
How could M7824 overcome some of the challenges associated with treatment failure to anti–PD-1/PD-L1 agents?
TGF-beta is a pleotropic cytokine that has many negative regulatory functions in patients with cancer. It is involved in immune suppression, angiogenesis, tumor metastasis (EMT) and resistance to chemotherapy. PDL1 also appears to remain an important checkpoint in patients who fail PD1/PDL1 blockade, it is just not sufficient. We reasoned that the combination of TGF-beta inhibition through sequestering (vacuuming up) TGF-beta and blocking PDL1 will be helpful to overcome primary-refractory disease and acquired resistance (initial response followed by progressive disease).
Could you tell us about the main findings obtained from the Phase I trial for M7824?
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Oncology Central or Future Science Group. [/userpro_private]