The investigational immunotherapeutic IMC-20D7S was safe, well tolerated, and showed signs of modest clinical activity for patients with advanced melanoma, according to results from a first-in-human phase I clinical trial.
Wolchok explained that even though immunotherapy has significantly improved outcomes for some patients with advanced melanoma, many patients have tumors that do not respond to currently available treatments or have tumors that initially respond but then become resistant to them.
"In this study, we evaluated the safety and early clinical activity of a new antimelanoma immunotherapy [IMC-20D7S]," said Wolchok. He went on to explain that IMC-20D7S is a therapeutic antibody that attaches to a molecule in melanoma cells called TYRP1 and that after attaching to the melanoma cells it recruits cells of the immune system to the area, and these cells then attack the melanoma cells.
Wolchok, Danny N. Khalil, MD, PhD, a medical oncology fellow working in Wolchok's laboratory, and colleagues enrolled 27 patients ages 44-84 with advanced melanoma in the clinical trial. All the patients had unresectable stage 3 or stage 4 disease that had progressed after or during prior treatment.
The study was designed to test escalating doses of IMC-20D7S in two different dosing schedules, an every-two-week schedule and an every-three-week schedule.
No patients had treatment-related adverse events classed as grade 3 or greater and there were no dose-limiting toxicities. Fourteen patients had low-grade treatment-related adverse events, most commonly fatigue and constipation. As a result, the maximum tolerated dose was not determined.
The disease-control rate, defined as stable disease or better, was 41 percent. One patient had a complete response, as assessed by RECIST1.1 criteria, which lasted almost six months. Ten patients had stable disease as the best response.
"We were pleased to see that IMC-20D7S was safe and none of the patients had high-grade serious adverse events related to treatment," said Wolchok. "Given that IMC-20D7S monotherapy resulted in only modest clinical activity for patients, I would anticipate that future studies will focus on evaluating agents such as this in combination with other treatments.
"The patients enrolled in this trial were all heavily pretreated; as a result, their immune systems may not have been sufficiently robust to be reinvigorated by IMC-20D7S," continued Wolchok. "We hope that we can increase the clinical activity of IMC-20D7S by using it in combination with other treatments or by using it as a tool to deliver chemotherapeutics or radioactive particles to the melanoma cells."
The study was funded by Lilly and the National Institutes of Health. Khalil is supported by an AACR-Amgen Inc. Fellowship in Clinical/Translational Cancer Research, a Daland Fellowship in Clinical Investigation from the American Philosophical Society, and a Young Investigator Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology. Wolchok receives grants and/or research funding from and/or acts as a consultant for Bristol-Myers Squibb, MedImmune, Merck Pharmaceuticals, Genentech, and Polynoma Pharmaceuticals.
Article: An Open-Label, Dose-Escalation Phase I Study of Anti-TYRP1 Monoclonal Antibody IMC-20D7S for Patients with Relapsed or Refractory Melanoma, Danny N. Khalil, Michael A. Postow, Nageatte Ibrahim, Dale L. Ludwig, Jan Cosaert, Siva Rama Prasad Kambhampati, Shande Tang, Dmitri Grebennik, John Sae Wook Kauh, Heinz-Josef Lenz, Keith T. Flaherty, F. Stephen Hodi, Donald P. Lawrence and Jedd D. Wolchok, Clinical Cancer Research, doi: 10.1158/1078-0432.CCR-16-1241, published 19 October 2016.