Immunocore Limited yesterday presented new biomarker research data for effects of Tebentafusp (IMCgp100) on patients with advanced uveal and cutaneous melanoma. Monotherapy treatment with the first-in-class ImmTAC® molecule tebentafusp was found to induce an immunologically potent response in patients. These findings, presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, provide additional insight into the mechanism of action of tebentafusp in patients with advanced melanoma and demonstrates the potential association with clinical outcomes.
Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Tebentafusp specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect T cells to recognize and kill tumor cells. Pivotal tebentafusp clinical trials are currently underway in metastatic uveal melanoma, a rare form of eye cancer.
Researchers analyzed data from the Phase 1 first-in-human clinical trial assessing the safety and tolerability of tebentafusp in 84 HLA-A2+ patients with metastatic melanoma (n=61 cutaneous, n=19 uveal, n=4 other) resistant to standard treatment regimens or for which no standard treatments exist. Highlights of the presented findings include:
- An association between a greater increase in serum CXCL10, a chemokine for T cells expressing CXCR3 receptor, and a greater transient reduction in peripheral CXCR3+CD8+ T cells, tumour shrinkage and longer overall survival (OS).
- Adverse events (AEs) were consistent with tebentafusp’s proposed mechanism of action with most AEs relating to on-target (gp100) off-tumour activity (e.g., rash, pruritus), or were cytokine mediated (e.g., pyrexia, hypotension).
“Further understanding of the potential association of mechanism of action with safety and activity is important in the success of novel immune therapies,” said Omid Hamid, MD, study investigator and Chief of Translational Research and Immunotherapy at The Angeles Clinic. “These data support the continued investigation of tebentafusp in cutaneous melanoma in addition to the pivotal trials in metastatic uveal melanoma already underway.”
Full news release: https://www.immunocore.com/news-hub/news/new-biomarker-research-builds-further-understanding-tebentafusp-imcgp100-mechanism-action-link-clinical-activity-advanced-melano