IMCgp100 is a therapy that Immunocore is developing to treat the skin cancer melanoma. This includes uveal melanoma, the most common type of eye cancer.

In early 2016 the U.S. Food and Drug Administration granted orphan drug status to IMCgp100 as  a treatment for uveal melanoma. That status is aimed at speeding up the therapy’s development and regulatory approval.

How IMCgp100 works

IMCgp100 is a bispecific antibody, meaning that it binds to two proteins at the same time. It works with immune T-cells. Part of IMCgp100 is a modified T-cell receptor that targets a protein called gp100 in melanoma cells. The other part is an antibody fragment that targets CD3, a protein receptor found on the surface of T-cells.

The T-cell receptor portion of IMCgp100 binds with gp100, which is overproduced in melanoma cells. Once IMCgp100 binds to gp100, the anti-CD3 portion redirects T-cells to kill melanoma cells.

IMCgp100 in clinical trials

Immunocore conducted an open-label Phase 1 clinical trial (NCT01211262) to evaluate the safety and tolerability of IMCgp100 in patients with advanced melanoma, including uveal melanoma. The results showed that the therapy was safe and triggered long-lasting responses in patients with both skin and eye melanoma. Some patients experienced toxicity at higher doses,  prompting researchers to limit treatment to a low dose.

Another Phase 1 trial (NCT02570308) is looking at IMCgp100’s safety and ability to treat advanced uveal melanoma. Researchers hope to reduce the toxicity seen in the first trial, maximizing MCgp100’s effectiveness.

An interim analysis of 19 patients showed that a 50 percent higher dose than the one used in the first trial was safe and effective. Patients also experienced a prolonged response to treatment and longer survival times. Seventy-three percent survived for a year after treatment, compared with 25 to 45 percent with other treatments.

The promising findings prompted the company to start a Phase 2 trial (NCT03070392) of IMCgp100 in patients with previously untreated uveal melanoma.

Immunocore is also studying IMCgp100 in combination with other therapies in a Phase 1/2 trial (NCT02535078) of patients with skin cancer that has spread to other tissue. The other therapies include the AstraZeneca drugs Imfinzi (durvalumab) and tremelimumab.


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