Dataset Information

Tebentafusp in the Treatment of Metastatic Uveal Melanoma: Patient Selection and Special Considerations.

ABSTRACT: Uveal melanoma (UM) is a rare type of melanoma with distinct features from cutaneous melanoma, low response rates to immune checkpoint inhibition, and poor survival rates. Tebentafusp, a bispecific antibody engaging T cells with gp 100 on HLA-A*02:01, was recently approved by the FDA as the first drug of its class and the first treatment approved by the FDA to treat UM. In this review, we summarize the preclinical and clinical data on tebentafusp for UM. We additionally discuss patient selection and the relevant challenges. For the literature search, PubMed search and relevant articles presented at international conferences were used.

SUBMITTER: Montazeri K

PROVIDER: S-EPMC9921510 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Tebentafusp in the Treatment of Metastatic Uveal Melanoma: Patient Selection and Special Considerations.

Montazeri Kamaneh K Pattanayak Vikram V Sullivan Ryan J RJ

Drug design, development and therapy 20230207

Uveal melanoma (UM) is a rare type of melanoma with distinct features from cutaneous melanoma, low response rates to immune checkpoint inhibition, and poor survival rates. Tebentafusp, a bispecific antibody engaging T cells with gp 100 on HLA-A*02:01, was recently approved by the FDA as the first drug of its class and the first treatment approved by the FDA to treat UM. In this review, we summarize the preclinical and clinical data on tebentafusp for UM. We additionally discuss patient selection ...[more]

PMID: 36785760

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Project description:Amivantamab is a bispecific antibody that recognizes epidermal growth factor receptor (EGFR) and MET proto-oncogene (MET). In May 2021, the Food and Drug Administration gave an accelerated approval of amivantamab for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertions (Exon20ins) who progressed after platinum-based chemotherapy. Amivantamab prevents ligand binding to EGFR and MET and the dimerization of the receptors suppressing the downstream signal transduction. Moreover, amivantamab determines antibody dependent cellular cytotoxicity and down regulation of cell surface proteins through internalization of the receptor and trogocytosis. Preliminary results of the Phase I/IB CHRYSALIS trial demonstrated an objective response rate of 40% with a median duration of response of 11.1 months (95% CI 9.6-not reached) in 81 patients treated with amivantamab with pretreated NSCLC with Exon20ins EGFR mutations. In a different cohort of the CHRYSALIS trial, patients with Ex19del and L858R EGFR mutations were enrolled after progression on osimertinib. 121 and 45 patients received amivantamab or a combination with lazertinib, a third-generation tyrosine kinase inhibitor, respectively. The objective response rate was 19% and 36% in patients treated with amivantamab alone or in combination with lazertinib, with a median progression-free survival of 6.9 (95% CI: 3.2-5.3) and 11.1 (95% CI: 3.7-9.5) months, respectively. All 20 patients with Ex19del and L858R EGFR mutations who received amivantamab and lazertinib as their first line treatment achieved an objective response. Amivantamab is currently under evaluation in Phase III clinical trials for the first line treatment of NSCLCs with Exon20ins EGFR mutations in combination with chemotherapy (PAPILLON), for the first line therapy of Ex19del and L858R mutated NSCLCs in combination with lazertinib (MARIPOSA) and in combination with chemotherapy and lazertinib in NSCLCs who progressed on osimertinib (MARIPOSA-2).

Project description:BackgroundTebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.MethodsWe report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level. The primary end point was overall survival.ResultsAt a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (hazard ratio for death, 0.68; 95% confidence interval, 0.54 to 0.87). The estimated percentage of patients surviving at 3 years was 27% in the tebentafusp group and 18% in the control group. The most common treatment-related adverse events of any grade in the tebentafusp group were rash (83%), pyrexia (76%), pruritus (70%), and hypotension (38%). Most tebentafusp-related adverse events occurred early during treatment, and no new adverse events were observed with long-term administration. The percentage of patients who discontinued treatment because of adverse events continued to be low in both treatment groups (2% in the tebentafusp group and 5% in the control group). No treatment-related deaths occurred.ConclusionsThis 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. (Funded by Immunocore; IMCgp100-202 ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).

Dataset Information

Tebentafusp in the Treatment of Metastatic Uveal Melanoma: Patient Selection and Special Considerations.

Publications

Tebentafusp in the Treatment of Metastatic Uveal Melanoma: Patient Selection and Special Considerations.

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