FDA APPROVED 1/25/2022, Kimmtrak, To treat unresectable or metastatic uveal melanoma
- T cell receptor α chain (synthetic human) fusion protein with T cell receptor β chain (synthetic human) fusion protein with immunoglobulin, anti-(human CD3 antigen) (synthetic scFv fragment)
- Protein Sequence
- Sequence Length: 695, 500, 195
1AIQMTQSPSS LSASVGDRVT ITCRASQDIR NYLNWYQQKP GKAPKLLIYY51TSRLESGVPS RFSGSGSGTD YTLTISSLQP EDFATYYCQQ GNTLPWTFGQ101GTKVEIKGGG GSGGGGSGGG GSGGGGSGGG SEVQLVESGG GLVQPGGSLR151LSCAASGYSF TGYTMNWVRQ APGKGLEWVA LINPYKGVST YNQKFKDRFT201ISVDKSKNTA YLQMNSLRAE DTAVYYCARS GYYGDSDWYF DVWGQGTLVT251VSSGGGGSDG GITQSPKYLF RKEGQNVTLS CEQNLNHDAM YWYRQDPGQG301LRLIYYSWAQ GDFQKGDIAE GYSVSREKKE SFPLTVTSAQ KNPTAFYLCA351SSWGAPYEQY FGPGTRLTVT EDLKNVFPPE VAVFEPSEAE ISHTQKATLV401CLATGFYPDH VELSWWVNGK EVHSGVCTDP QPLKEQPALN DSRYALSSRL451RVSATFWQDP RNHFRCQVQF YGLSENDEWT QDRAKPVTQI VSAEAWGRAD
1AQQGEEDPQA LSIQEGENAT MNCSYKTSIN NLQWYRQNSG RGLVHLILIR51SNEREKHSGR LRVTLDTSKK SSSLLITASR AADTASYFCA TDGSTPMQFG101KGTRLSVIAN IQKPDPAVYQ LRDSKSSDKS VCLFTDFDSQ TNVSQSKDSD151VYITDKCVLD MRSMDFKSNS AVAWSNKSDF ACANAFNNSI IPEDT
|bridge||Cys-23 – Cys-88||disulfide bridge|
|bridge||Cys-153 – Cys-227||disulfide bridge|
|bridge||Cys-281 – Cys-349||disulfide bridge|
|bridge||Cys-401 – Cys-466||disulfide bridge|
|bridge||Cys-427 – Cys-157′||disulfide bridge|
|bridge||Cys-23′ – Cys-89′||disulfide bridge|
|bridge||Cys-132′ – Cys-182′||disulfide bridge|
The most common side effects include cytokine release syndrome, rash, pyrexia (fever), pruritus (itching), fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting.
Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager. It was approved for medical use in the United States in January 2022.
Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager used to treat unresectable or metastatic uveal melanoma.
Tebentafusp is a gp100 peptide-HLA-directed CD3 T cell engager.5 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.1,2
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.1 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.5
FDA approves tebentafusp-tebn for unresectable or metastatic uveal melanoma
On January 25, 2022, the Food and Drug Administration approved tebentafusp-tebn (Kimmtrak, Immunocore Limited), a bispecific gp100 peptide-HLA-directed CD3 T cell engager, for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
Efficacy was evaluated in IMCgp100-202 (NCT03070392), a randomized, open-label, multicenter trial of 378 patients with metastatic uveal melanoma. Patients were required to be HLA-A*02:01 genotype positive identified by a central assay. Patients were excluded if prior systemic therapy or localized liver-directed therapy were administered. Prior surgical resection of oligometastatic disease was permitted. Patients with clinically significant cardiac disease or symptomatic, untreated brain metastases were excluded.
Patients were randomized (2:1) to receive tebentafusp-tebn (N=252) or investigator’s choice (N=126) of either pembrolizumab, ipilimumab, or dacarbazine. Tebentafusp-tebn was administered weekly by intravenous infusion at 20 mcg on day 1, 30 mcg on day 8, 68 mcg on day 15 and every subsequent week until disease progression or unacceptable toxicity. The main efficacy outcome measure was overall survival (OS). An additional efficacy outcome was investigator-assessed progression-free survival (PFS) per RECIST 1.1. Median OS was 21.7 months (95% CI: 18.6, 28.6) for patients treated with tebentafusp-tebn and 16 months (95% CI: 9.7, 18.4) in the investigator’s choice arm (HR=0.51, 95% CI: 0.37, 0.71, p<0.0001) PFS was 3.3 months (95% CI: 3, 5) for those receiving tebentafusp-tebn and 2.9 months (95% CI: 2.8, 3) in the investigator’s choice arm (HR=0.73, 95% CI: 0.58, 0.94, p=0.0139).
The most common adverse reactions (≥30%) were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common laboratory abnormalities (≥50%) were decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate.
The recommended tebentafusp-tebn dose administered intravenously is:
- 20 mcg on day 1,
- 30 mcg on day 8,
- 68 mcg on day 15, and
- 68 mcg once weekly thereafter.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and the United Kingdom’s Medicines and Healthcare product Regulatory Agency (MHRA). The application reviews may be ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review, breakthrough designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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|Other names||IMCgp100, tebentafusp-tebn|
|License data||US DailyMed: Tebentafusp|
|Legal status||US: ℞-only |
Efficacy was evaluated in IMCgp100-202 (NCT03070392), a randomized, open-label, multicenter trial of 378 participants with metastatic uveal melanoma. Participants were required to be HLA-A*02:01 genotype positive identified by a central assay. Participants were excluded if prior systemic therapy or localized liver-directed therapy were administered. Prior surgical resection of oligometastatic disease was permitted. Participants with clinically significant cardiac disease or symptomatic, untreated brain metastases were excluded.
- ^ Jump up to:a b c d e f https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf
- ^ Jump up to:a b c d e f g h i j k l “FDA approves tebentafusp-tebn for unresectable”. U.S. Food and Drug Administration (FDA). 25 January 2022. Retrieved 28 January 2022. This article incorporates text from this source, which is in the public domain.
- “Tebentafusp”. Drug Information Portal. U.S. National Library of Medicine.
- Clinical trial number NCT03070392 for “Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma” at ClinicalTrials.gov
/////////////////Tebentafusp-tebn, Kimmtrak, priority review, breakthrough designation, orphan drug designation, Immunocore Limited, IMCGP100, APPROVALS 2022, FDA 2022
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