Immunocore presented data showing that its leading investigational immunotherapy, IMCgp100, leads to durable tumor responses and strong survival rates in patients with advanced uveal melanoma, following two Phase 1 clinical trials.
The study, “Safety, efficacy and biology of the gp100 TCR-based bispecific T cell redirector, IMCgp100 in advanced uveal melanoma in two Phase 1 trials,” was presented at the Society for Immunotherapy of Cancer’s (SITC) 32nd Annual Meeting in National Harbor, Maryland.
While skin melanoma has long been treated with drugs that boost immune responses, called immune checkpoint inhibitors, they have shown limited effectiveness in patients with uveal melanoma, which arises from the pigment cells of the eye.
In an attempt to develop therapies for melanoma and uveal melanoma patients, Immunocore developed a new immunotherapy that targets the gp100 molecule — found mostly on melanoma cells — while activating tumor-killing immune cells. To date, the therapy has been tested in two Phase 1 trials.
The first-in-human Phase 1 study (NCT01211262) was designed to establish the best weekly dose strategy for IMCgp100 and to look for signs that the therapy worked as intended.
The trial enrolled patients with late-stage and unresectable (not suitable for surgery) melanoma, 16 of whom had uveal melanoma.
Overall, the maximum tolerated dose was established as 600 ng/kg. But for patients with larger disease diameters, researchers saw that higher doses were best at inducing a response. The team also found that most adverse events happened within the first two weeks.
Researchers thus hypothesized that increased exposure to IMCgp100 in the weeks following the occurrence of more severe toxicity could lead to a better anti-tumor response in tumors with an unfavorable tumor microenvironment, such as uveal melanoma.
In the second Phase 1 trial (NCT02570308), which is still recruiting participants, Immunocore is testing if dosing patients with high doses of IMCgp100 after the first two weeks is effective at improving patient survival rates.
The study has already enrolled 19 advanced uveal melanoma patients who received two weekly doses of IMCgp100 at a dose level below 600 ng/kg, followed by a dose escalation in week 3.
Participants lived for a median of 5.6 months before seeing their disease progress. Also, the treatment demonstrated a one-year progression-free survival rate of 62% and a one-year survival rate of 73%, which compares favorably with other therapies where only 25-45% of patients are still alive after the first year.
“Metastatic uveal melanoma is a condition with exceptionally high unmet medical need with no current standard of care in this setting. No therapies to date have shown survival benefits in trials,” Richard Carvajal, head of experimental therapeutics at Columbia University, said in a press release. “The exciting one-year overall survival and progression-free survival data we have observed with IMCgp100 have given us confidence to move into pivotal trials measuring survival in this disease setting.”