A novel immunotherapy antibody was safe and showed modest antitumor activity in a phase I clinical trial 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.”
Tebentafusp Continues to Demonstrate Benefit in Metastatic Uveal Melanoma
January 4th 2024Results from a long-term analysis of the phase 3 IMCgp100-202 trial indicate that tebentafusp results in better disease control and long-lasting responses in those with HLA-A*02:01–positive, previously untreated metastatic uveal melanoma.