There are several emerging treatments with novel modes of action showing promise for improved patient outcomes, especially those targeting the BRCA mutation subgroup, as well as poly-ADP ribose polymerase (PARP) inhibitors. There is a randomized POLO study looking at maintenance PARP inhibitors after patients have responded to platinum-based chemotherapy. Those are very novel approaches. The other novel approaches are defining the damage repair deficiency (DDR) subtype and giving those patients platinum-based and PARP-based treatments. We are participating in a phase 3 hyaluronic-based clinical trial that is looking at a novel enzyme in patients with a subtype of pancreas cancer that has been described as HA high (high expression of hyaluronan, defined as >50% expression, or tumor volume, of this hyaluronan protein). Right now, the phase 2 study looks interesting. The data in the HA subtype look better than in the overall population, although the primary endpoints were met in the overall population. The progression-free survival was not robust in the overall population, but in the HA high subtype, it seemed pretty robust. I think it is interesting that drugs are now being developed to target the tumor stroma, which we know is a very characteristic attribute of pancreas cancer. We have also participated in studying the bruton tyrosine kinase (BTK) inhibitor, which is also a stromal targeting agent. I think that is the group of studies that most interest me. There are also several ongoing immunotherapy studies that, unfortunately, have not been showing much promise, but our colleagues who study immunotherapy do believe that if they have the right combination of medications or interventions, they will be able to elicit a response. I think those are the most promising and interesting from my perspective.

We are also enrolling patients in the pegylated recombinant human hyaluronidase (PEGPH20) trial, and I think that is an interesting trial. It has a putative biomarker in hyaluronan. As Dr Hendifar explained, there have been some interesting data with stemness kinase inhibitors and the BBI608 molecule (napabucasin). I think the issue is that a lot of these trials are very early, and in pancreas cancer we’ve had so much disappointment with novel combinations and new drugs. It does feel like the dominoes are starting to fall, but it’s definitely a long road. We are still treating a disease in which cytotoxic chemotherapy is the backbone as the major treatment of choice, and it does not appear that it will be shifting anytime soon – although these shifts tend to go quickly. With respect to immunotherapies, turning pancreas cancer – a really cold tumor, and an immunologically protected cancer – into something where we can really get some immune cell infiltration has posed numerous challenges. We are really trying different combinations to get pancreas cancer to start to respond to some of these immunological agents. This is something that we are really striving for as immunotherapy has taken over oncology in general, but it just has not made its way into pancreas cancer yet.