Immunocore Announces FDA Approval of Kimmtrak: The First T Cell Receptor (TCR) Therapy for Unresectable or Metastatic Uveal Melanoma

Today, Immunocore announced that the U.S. FDA has approved its innovative therapy Kimmtrak (tebentafusp-tebn) for marketing to treat a specific type of uveal melanoma. The press release noted that this approval marks several firsts: it is the first therapy approved by the FDA for treating unresectable or metastatic uveal melanoma. It is also the first T cell receptor (TCR) therapy to receive regulatory approval, as well as the first bispecific T-cell engager approved by the FDA for treating solid tumors.

As an innovative bispecific protein, Kimmtrak is composed of two parts: one end is a high-affinity soluble T-cell receptor, and the other end is an anti-CD3 immune effector domain. This therapy specifically targets gp100, an antigen expressed in melanocytes and melanoma. Previously, this "first-in-class" therapy has received Breakthrough Therapy Designation, Fast Track Designation, Orphan Drug Designation, and Priority Review Designation from the U.S. FDA.

▲Mechanism of Action of Kimmtrak (Image Source: Reference [3])

The approval of Kimmtrak was based on the results of a Phase 3 clinical trial. The trial enrolled previously untreated patients with uveal melanoma who were HLA-A*02:01 positive. Patients were randomly assigned in a 2:1 ratio to receive either Kimmtrak or an active control drug. Data published last September in The New England Journal of Medicine indicated that, as a first-line treatment, Kimmtrak reduced the risk of death by 49% (HR=0.51, 95% CI: 0.37, 0.71, p<0.0001). The median overall survival was 21.7 months in the Kimmtrak group and 16.0 months in the active control group. In terms of safety, treatment-related adverse events were manageable.

▲Overall survival data from the Phase 3 clinical trial of Kimmtrak (Image source: Reference [3])

Immunocore's ImmTAC technology platform focuses on developing a series of bispecific biologics that enable the immune system to re-identify and kill cancer cells. Kimmtrak is the first therapy to emerge from this platform. Other molecules in development on this platform have a similar design, modifying soluble T-cell receptors to recognize intracellular cancer antigens and using an anti-CD3 immune-effector domain to kill these cancer cells with extremely high affinity and selectivity. Due to the ability of T cells to infiltrate human tumors, molecules developed on the ImmTAC platform have the potential to target solid tumors without considering the tumor’s mutational burden. These molecules also hold potential for treating blood cancers.

▲Immunocore's R&D Pipeline (Image Source: Reference [4])

References:

[1] Immunocore announces FDA approval of KIMMTRAK® (tebentafusp-tebn) for the treatment of unresectable or metastatic uveal melanoma, Retrieved January 26, 2022, from https://www.globenewswire.com/news-release/2022/01/26/2373344/0/en/Immunocore-announces-FDA-approval-of-KIMMTRAK-tebentafusp-tebn-for-the-treatment-of-unresectable-or-metastatic-uveal-melanoma.html

[2] UPDATED: FDA hurries up a quick approval for the world's first TCR — after a 14-year R&D trek, Retrieved January 26, 2022, from https://endpts.com/breaking-fda-hurries-up-a-quick-approval-for-the-worlds-first-tcr-after-a-14-year-rd-trek/

[3] Nathan et al., (2021). Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. NEJM, DOI: 10.1056/NEJMoa2103485

[4] Immunocore Official Website, Retrieved January 26, 2022, from https://www.immunocore.com/

(Original text has been abridged)

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