Axel Hauschild, MD, on Melanoma: Findings From the PIVOTAL Trial of Daromun vs Surgery

I'd like to report about a study which was called PIVOTAL. It's a clinical trial on Daromun, a new agent which was not discovered so far in a Phase III trial. The trial design is very simple. It was a one-to-one randomization of 260 patients. In one arm is surgery alone for fully resectable stage III melanoma patients with either lymph node or skin metastases. The other arm was a prior treatment, prior to surgery, with four consecutive injections intratumorally, for the skin and lymph nodes with Daromun. I need to explain Daromun briefly because the agent is new. It's a composition of an L19 antibody directed to fibronectin, which is a crucial molecule for the development of neovascularization, particularly in tumors. And this is linked to interleukin 2, which enhances the number of tumor infiltrating lymphocyte in the tumor, and in addition to another antibody, which is linked to the drug, which is very important for the tumor necrosis, the tumor necrosis factor alpha. It's two component brought to one injection, and this has been done four consecutive times. The result of the study is that the primary endpoint, which is relapse three survival is positive. A positive randomized phase III trial and the hazard ratio is 0.59, corresponding to a more than 40% reduction of the risk for recurrence and the risk of death. Secondary endpoints as distant metastasis-free survival were also positive. In the same ballpark, the hazard ratio here is .60, so 40% reduction in the risk to develop distant metastases. I need to mention that there was a study amendment which allowed us to evaluate the tumor specimens, which have been treated by Daromun, and the rate of pathologically confirmed complete responses is 21%. Further read shots on this is following. Of note, there was almost no systemic toxicity. All of the toxicities were local. It was very well tolerated, it was manageable, and the mean number of administered cycles was three, the median number was four. Almost all patients got the full package of four injections. In general, I need to say and conclude, positive phase III trial, met the primary endpoint and it will be submitted primarily to the European medical agencies very soon and we will see what happens. But I hope that we will have a new drug in our treatment armamentarium for stage three melanoma patients with fully resectable disease in the neoadjuvant intention.