MedPath

Tebentafusp

Generic Name
Tebentafusp
Brand Names
Kimmtrak
Drug Type
Biotech
CAS Number
1874157-95-5
Unique Ingredient Identifier
N658GY6L3E
Background

Tebentafusp is a gp100 peptide-HLA-directed CD3 T cell engager. It is a bispecific, fusion protein and first-in-class drug of immune-mobilizing monoclonal T cell receptors against cancer (ImmTACs), a recently developed cancer immunotherapy with a novel mechanism of action. ImmTACs bind to target cancer cells that express a specific antigen of interest and recruit cytotoxic T cells to lyse the cells, such as melanocytes.

Uveal melanoma is a rare ocular tumour with often poor prognosis and limited treatment options. Even after surgical ablation or removal of the ocular tumour, almost 50% of patients with uveal melanoma develop metastatic disease. On January 26, 2022, tebentafusp was first approved by the FDA for the treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma. This approval marks the first bispecific T cell engager to be approved by the FDA to treat a solid tumour and being the first and only therapy for the treatment of unresectable or metastatic uveal melanoma to be approved by the FDA. Tebentafusp was subsequently approved for the same indication in the EU in April 2022.

Indication

Tebentafusp is indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.

Associated Conditions
Metastatic Uveal Melanoma, Unresectable Uveal Melanoma

CDMO Market Report: Key Regulatory Approvals and Clinical Advances in March-April 2025

• Multiple CDMOs secured significant contract manufacturing opportunities as regulatory bodies approved new indications for established drugs, particularly in oncology and rare diseases. • AstraZeneca's portfolio saw substantial growth with expanded approvals for Imfinzi, Tagrisso, and Lynparza, strengthening partnerships with contract manufacturers including Lonza, Dottikon, and Samsung Biologics. • Contract manufacturers supporting treatments for autoimmune conditions showed strong performance, with Argenx's Vyvgart Hytrulo receiving expanded indications for myasthenia gravis and CIDP.

Immunocore Reports Strong KIMMTRAK Sales Growth and Advances Clinical Pipeline in 2024

• KIMMTRAK achieved $310 million in net sales for 2024, with $84.1 million in Q4, marking 11 consecutive quarters of growth and launches in 14 new territories. • The company advanced its PRAME portfolio with first patient randomization in Phase 3 PRISM-MEL-301 trial and continued enrollment in combination studies for ovarian cancer and NSCLC. • Immunocore maintained strong financial position with $820.4 million in cash and marketable securities, while progressing autoimmune and infectious disease programs.

Immunocore Advances Clinical Pipeline with Multiple Phase 3 Trials and New Drug Candidates

• KIMMTRAK shows strong commercial performance with Q3 2024 revenues reaching $80.2 million, representing 28% growth year-over-year. • Company initiates multiple Phase 3 trials across melanoma indications, including PRISM-MEL-301 and TEBE-AM studies, with first data expected in 2026. • Immunocore expands pipeline with first-in-class PIWIL1-targeted therapy and PRAME-targeted IMC-P115C, demonstrating progress in novel cancer immunotherapy development.

Immunocore Advances Novel Immunotherapies Targeting PRAME and PIWIL1 in Phase 1 Trials

• Immunocore has dosed the first patient in a Phase 1 trial of IMC-P115C, a half-life extended ImmTAC candidate targeting PRAME, designed to improve patient convenience through less frequent administration. • The Phase 1 trial will assess the safety, pharmacokinetics, and clinical activity of IMC-P115C in HLA-A*02:01-positive patients with advanced cancers expressing PRAME. • Immunocore has also dosed the first subject in a Phase I/II trial of IMC-R117C, an ImmTAC molecule targeting PIWIL1, for treating colorectal and other gastrointestinal cancers. • IMC-R117C will be evaluated as a single agent and in combination with other therapies, with the trial assessing tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics.

Phase 3 Trial Initiates to Evaluate Kimmtrak in Non-Metastatic Uveal Melanoma

• The phase 3 ATOM trial is evaluating Kimmtrak versus observation in patients with non-metastatic uveal melanoma at high risk of relapse. • The trial aims to determine if Kimmtrak can prevent or delay relapse in patients who have undergone primary treatment for uveal melanoma. • The study will enroll 290 HLA-A*02:01-positive patients and assess overall survival, safety, tolerability, and quality of life. • Kimmtrak was previously approved for unresectable or metastatic uveal melanoma, showing manageable side effects like fever and rash.

NHS England Fast-Tracks Tebentafusp for Rare Eye Cancer, Uveal Melanoma

• The NHS has approved tebentafusp (Kimmtrak) for uveal melanoma, a rare eye cancer affecting 500-600 people annually in the UK. • Tebentafusp, a pioneering immunotherapy, extends survival by attaching to cancer cells and T cells, enhancing immune response. • Clinical trials showed a 27% three-year survival rate with tebentafusp, compared to 18% with standard checkpoint inhibitors. • The treatment, developed by Immunocore, marks a significant advancement, offering new hope for patients with limited options.

Bispecific Antibodies: Promising Advances Amid Adoption Challenges in Cancer Treatment

• Bispecific antibodies represent a significant advancement in cancer immunotherapy, targeting both tumor antigens and immune cells to enhance cytotoxicity without requiring patient-derived cells like CAR-T therapy. • Despite clinical promise with nine FDA-approved bispecific antibodies, adoption faces challenges including transition between inpatient/outpatient settings, insurance coverage, adverse event management, and financial barriers in community settings. • Recent approvals of Mosunetuzumab, Glofitamab, and Epcoritamab have shown impressive response rates in relapsed/refractory indolent B-cell lymphomas, with manageable toxicity profiles when using step-up dosing strategies.

Novel Treatment Landscape Expands for Uveal Melanoma with Multiple Promising Therapies in Development

• Recent FDA approvals of Kimmtrak and Hepzato mark significant breakthroughs in uveal melanoma treatment, offering new options for patients with metastatic disease. • IDEAYA Biosciences' darovasertib-crizotinib combination enters phase 3 trials, potentially expanding treatment options for both HLA-A2 positive and negative metastatic uveal melanoma patients. • Multiple innovative approaches are advancing through clinical development, including Roche's T-cell engager RO7293583 and iOnctura's novel PI3Kδ inhibitor IOA-244.
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