{"id":26620,"date":"2020-12-12T12:00:00","date_gmt":"2020-12-12T12:00:00","guid":{"rendered":"http:\/\/ddeaf5a1bcba96cc44c8c14ed92d0856"},"modified":"2024-11-03T15:15:51","modified_gmt":"2024-11-03T15:15:51","slug":"promising-results-are-provided-by-tebentafusp-in-metastatic-uveal-melanoma","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/promising-results-are-provided-by-tebentafusp-in-metastatic-uveal-melanoma\/","title":{"rendered":"Promising Results Are Provided by Tebentafusp in Metastatic Uveal Melanoma"},"content":{"rendered":"

Tebentafusp (IMCgp100), a novel bispecific molecule that redirects T-cells showed clinical benefit, including target lesion reduction, in patients with metastatic uveal melanoma, according to phase II study findings presented at the ESMO Immuno-Oncology Virtual Congress 2020<\/a>, held from 9 to 12 December 2020.<\/strong><\/p>\n

Joseph J. Sacco of the Medical Oncology Department, Clatterbridge Cancer Centre and University of Liverpool, UK explained that tebentafusp is a bispecific fusion protein comprising an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100-positive (gp100+) cells. High expression of gp100 is seen in melanocytes, and melanoma cells.<\/p>\n

Dr Sacco and colleagues conducted this phase II, multi-centre study evaluating safety and efficacy of tebentafusp in HLA-A*0201-positive patients with metastatic uveal melanoma. Phase I of this study determined the phase II dose as 68 mcg.1<\/sup><\/p>\n

All patients received treatment at 24 centres with a regimen of weekly intravenous doses of 20 mcg C1D1, 30 mcg C1D8, and 68 mcg of C1D15+.<\/p>\n

Of the 127 patients treated, 50% were male, 70% had ECOG performance status 0, and 58% had baseline LDH exceeding the upper limit of normal. All of the patients had received \u22651 prior therapy in the metastatic setting. Many (34%) patients had received \u22652 prior treatments, including liver directed therapy (LDT) in 45% of patients and 73% of patients had received immunotherapy; of these 65% received anti-PD1, and 31% of patients received anti-CTLA4 therapies.<\/p>\n

Objective response rate (ORR) per RECIST v1.1 assessed by independent central review (ICR), served as the primary study endpoint and secondary endpoints included safety, overall survival (OS), and progression-free survival (PFS).<\/p>\n

Following tebentafusp, the ORR was 5% (95% confidence interval [CI] 1.8%-10.0%), all of which were partial responses (PRs). Stable disease was achieved by 45% of patients.<\/p>\n

The median duration of response was 8.7 months.<\/p>\n

Of the 116 patients with evaluable tumours, 44% demonstrated a reduction in target lesions that included immune-related responses.<\/p>\n

With median follow-up of 19.6 months, the median OS was 16.8 months (95% CI 12.9- 21.3). The 12- and 18-month OS rates were 62% and 45%, respectively.<\/p>\n

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\"Promising-Results-Are-Provided-by-Tebentafusp-in-Metastatic-Uveal-Melanoma\"
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Tebentafusp treatment is associated with promising overall survival in patients with metastatic uveal melanoma compared to historical data.<\/p>\n

\u00a9 Joseph J. Sacco.<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n<\/div>\n

Median PFS was 2.8 months.<\/p>\n

In patients demonstrating any reduction in a target lesion, the 12-month OS rate improved to 86%.<\/p>\n

Rash was an indicator of improved overall survival<\/h4>\n

The most commonly reported treatment-related adverse events (TRAEs) were generally cutaneous and likely linked to targeting gp100+ melanocytes, or cytokine mediated due to T-cell activation. TRAEs included pyrexia (80%), pruritus (67%), and chills (64%). Grade \u22653 TRAEs of maculo-papular rash occurred in 13% of patients, hypotension in 8%, and AST increased and hypophosphatemia were each reported in 5% of patients. In most patients, TRAEs decreased in frequency and severity after the first 3 doses of tebentafusp.<\/p>\n

Cytokine release syndrome (CRS; Lee 2019 criteria) was reported in 86% of patients; CRS Grade 3 was reported in 3% of patients and 1% of patients experienced Grade 4 CRS.<\/p>\n

There were no Grade 5 TRAEs.<\/p>\n

Patients (64%) developing rash within 7 days of tebentafusp initiation demonstrated superior median OS of 22.5 months compared to 10.3 months in patients with no rash.<\/p>\n

Conclusions<\/h4>\n

The investigators noted that although the primary endpoint showed only a 5% ORR, this was accompanied by a reduction in target lesion for 44% of patients. They further pointed out that the 12-month OS rate of 62% in patients overall was increased to 86% in patients achieving target lesion reduction, which they considered promising.<\/p>\n

According to the authors, TRAEs were generally predictable and manageable; furthermore, they decreased in frequency and severity following the first few doses and were consistent with the proposed mechanism of action.<\/p>\n

Tebentafusp is being studied further and is currently being evaluated in a randomised pivotal study with a primary endpoint of overall survival. This has reached its pre-defined boundaries for statistical significance of the primary endpoint of OS in its first pre-planned interim analysis with a hazard ratio of 0.51 in favour of tebentafusp over investigator choice, according to a recent press release<\/a>.<\/p>\n

Funding was reported from Immunocore Ltd.<\/p>\n

Citation<\/h4>\n
    \n
  1. Sato T, Nathan PD, Hernandez-Aya L, Sacco JJ, et al. Journal of Clinical Oncology<\/em> 2018;36:15_suppl:9521-9521.   <\/strong><\/li>\n<\/ol>\n

    Reference<\/h4>\n

    64MO \u2013 Sacco JJ, Carvajal R, Butler MO, et al.<\/em> A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM). ESMO Immuno-Oncology Virtual Congress 2020<\/a> (9-12 December).<\/p>\n

    Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

    Tebentafusp (IMCgp100), a novel bispecific molecule that redirects T-cells showed clinical benefit, including target lesion reduction, in patients with metastatic uveal melanoma, according to phase II study findings presented at the ESMO Immuno-Oncology Virtual Congress 2020, held from 9 to 12 December 2020. Joseph J. Sacco of the Medical Oncology Department, Clatterbridge Cancer Centre and […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-26620","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26620","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=26620"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26620\/revisions"}],"predecessor-version":[{"id":45472,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26620\/revisions\/45472"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=26620"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=26620"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=26620"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}