The investigational immunotherapeutic IMC-20D7S was found to be well tolerated and somewhat active in patients with advanced melanoma, including one complete response, according to the results of a phase I/Ib trial reported by Danny N. Khalil, MD, PhD, and colleagues in Clinical Cancer Research.
IMD-20D7S is a recombinant human IgG1 monoclonal antibody targeting TYRP1 on melanoma cells. Given the therapy’s mechanism of action, further investigation of this agent in combination with checkpoint blockade therapies, such as anti–PD-1 (programmed cell death protein 1) and anti–CTLA-4 (cytotoxic T-lymphocyte–associated protein 4), is warranted, according to the study findings.
The study was an open-label, dose-escalation phase I/Ib study. There were 27 patients enrolled in the study between 2010 and 2012, of whom 16 were men and 11 were women, ranging in age from 44 to 84 years. All study participants had unresectable stage III or IV melanoma with measurable disease as per RECIST (Responce Evaluation Criteria in Solid Tumors) 1.1. Patients who progressed after or during at least one line of treatment or for whom standard therapy was not indicated were included in the study.
The study tested escalating doses of IMC-20D7S in two different dosing schedules: an every 2-week schedule (arm A), with a cycle composed of 4 weeks, and an every 3-week schedule (arm B), with a cycle composed of 6 weeks.
The most common adverse events among the 27 patients were fatigue and constipation, experienced by 9 (33%) and 8 (30%) patients, respectively. There were no serious adverse events related to treatment, no discontinuations of treatment due to adverse events, and no treatment-related deaths.
Given the absence of dose-limiting toxicities, a maximum tolerated dose was not defined, but a provisional maximum tolerated dose was established at the 20 mg/kg every 2-week dose, based on serum concentration and safety data. One patient experienced a complete response, which lasted almost 6 months. A disease control rate, defined as stable disease or better, of 41% was observed.
“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 Jedd D. Wolchock, MD, PhD, Chief of the Melanoma and Immunotherapeutics Service and Associate Director of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center in New York; Director of the Parker Institute for Cancer Immunotherapy; and a coauthor of this study, in a statement.
“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 invigorated by IMC-20D7S. 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.”
Funding for this study was provided by Lilly and the National Institutes of Health. Dr. Khalil is currently supported by a fellowship in Clinical/Translational Cancer Research from the American Association for Cancer Research and Amgen; in Clinical Investigation from the American Philosophical Society; and through a Young Investigator Award from the Conquer Cancer Foundation and ASCO.