New Immunotherapeutic Tested in Clinical Trial
An investigational immunotherapeutic was safe, tolerable, and showed some activity against melanoma in a phase I clinical trial
The investigational immunotherapeutic IMC-20D7S was safe, well tolerated, and had signs of modest clinical activity for patients with advanced melanoma, according to results from the first-ever clinical trial evaluating the potential new melanoma treatment. The results were published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR).
“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 the senior author of the study, Jedd D. Wolchok, MD, PhD, the Lloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation and chief of the Melanoma & Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center (MSK) in New York.
Given that IMC-20D7S monotherapy resulted in only modest clinical activity for patients, Wolchok, who is also director of the Parker Institute for Cancer Immunotherapy and associate director of the Ludwig Center for Cancer Immunotherapy at MSK, anticipates that future studies will focus on evaluating agents such as this in combination with other treatments.
Melanoma is the most deadly form of skin cancer. The National Cancer Institute estimates that there will be more than 10,000 melanoma deaths in the United States in 2016.
Immunotherapy has dramatically improved outcomes for some patients with advanced forms of the disease. However, many patients have melanoma that does not respond to immunotherapy or that progresses after initially responding. As a result, researchers are looking for ways to extend the benefit of immunotherapy for these patients.
One approach is to identify new immunotherapeutics with activity against melanoma.
In this study, Wolchok, Danny N. Khalil, MD, PhD, a medical oncology fellow working in Wolchok’s laboratory who is supported in part by an AACR-Amgen Inc. Fellowship in Clinical/Translational Cancer Research, and colleagues evaluated the safety and early clinical activity of IMC-20D7S.
IMC-20D7S works by attaching to a molecule in melanoma cells called TYRP1. After attaching to TYRP1, it recruits cells of the immune system to the area, and these cells attack and destroy the melanoma cells.
The researchers enrolled 27 patients ages 44-84 with advanced melanoma that had progressed after or during prior treatment in the trial.
The trial tested escalating doses of IMC-20D7S in two different dosing schedules, an every-two- week schedule and an every-three-week schedule.
No patients had serious treatment-related adverse events and there were no dose-limiting toxicities. Fourteen patients had low grade treatment-related adverse events, most commonly fatigue and constipation.
The disease-control rate, defined as stable disease or better, was 41 percent. One patient had a complete response that lasted almost six months. Ten patients had stable disease as the best response.
“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,” said 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. 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.
