Anti-TYRP1 Monoclonal Antibody Shows Activity in Advanced Melanoma

A novel immunotherapy antibody was safe and showed modest antitumor activity in a phase I clinical trial in advanced melanoma. Of 27 patients with metastatic melanoma treated, one had a complete response. The disease control rate was 41% including ten patients (37%) with stable disease. The results of the early-stage trial are published in Clinical Cancer Research.

The immunotherapy, IMC-20D7S, is a recombinant human monoclonal antibody that targets the tyrosinase-related protein-1 (TYRP1), a transmembrane glycoprotein specifically expressed in melanocytes and melanoma cells.

“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 study author Jedd D. Wolchok, MD, PhD, the chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center in New York City in a statement. “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.”

According to the study authors, there is scientific rationale to test the combination of IMC-20D7S with current immunotherapies used to treat melanoma including the immune checkpoint-targeting anti-PD1 (programmed cell death protein 1) antibodies, nivolumab (Opdivo) and pembrolizumab (Keytruda), and the anti-CTLA-4 (cytotoxic T-lymphocyte–associated protein 4) antibody, ipilimumab (Yervoy).

The novel TYRP1-targeting antibody may trigger an antitumor T-cell response through

antibody-dependent cell-mediated phagocytosis which suggests that its efficacy may be complimentary or synergistic with immune checkpoint antibody therapies.

Danny N. Khalil, MD, PhD, a medical oncology fellow at the Memorial Sloan Kettering Cancer Center in New York City and his study co-authors enrolled 27 unresectable stage III or stage IV melanoma patients in an open-label dose-escalation phase I/Ib study. Patient age ranged from 44 to 84 years. The study authors tested escalating doses given either on an every 2-week or every 3-week schedule. The maximum tolerated dose was established as 20 mg/kg every 2 weeks.

The most common adverse events were fatigue, experienced by nine patients (33%) and constipation, experienced by eight patients (30%). No patients discontinued treatment due to adverse events and there were no serious adverse events related to treatment on trial.

The patient with a complete response, measured at 24 weeks, was a 67-year-old man with ileal metastases.

“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.”