Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)

February 23, 2026 updated by: Immunocore Ltd

Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination With Pembrolizumab Versus Investigator's Choice in HLA-A*02:01-positive Participants With Previously Treated Advanced Melanoma (TEBE-AM)

The purpose of this study is to evaluate the efficacy and safety of tebentafusp-based regimens, including tebentafusp monotherapy and in combination with anti-PD1 vs investigator choice (including clinical trials of investigational agents, salvage therapy per local standard of care [SoC], best supportive care [BSC] on protocol survivor follow up) in patients with advanced non-ocular melanoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase 3 (as upon conversion to phase 3 there were no changes to the arms listed herein), multicenter, open-label study to evaluate the efficacy and safety of tebentafusp as monotherapy (Arm A) and in combination with pembrolizumab (Arm B) compared with standard of care or best supportive care (Arm C) in participants with non-ocular advanced melanoma who have progressed on a prior anti-PD(L)1 regimen, received an approved anti-CTLA4 regimen and, if the participant has a BRAF mutation, a prior BRAF tyrosine kinase inhibitor (TKI) regimen.

Study Type

Interventional

Enrollment (Estimated)

540

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Wollstonecraft, New South Wales, Australia, 2065
        • Recruiting
        • Melanoma Institute Australia
    • Queensland
      • Greenslopes, Queensland, Australia, 4120
        • Recruiting
        • Gallipoli Medical Research Foundation (GMRF)
      • Woolloongabba, Queensland, Australia, 4102
        • Recruiting
        • Princess Alexandra Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Alfred Health
  • Austria
      • Graz, Austria, 8036
        • Recruiting
        • Lkh - Universitaetsklinikum Graz
      • Linz, Austria, 4020
        • Recruiting
        • Kepler Universitätsklinikum
      • Salzburg, Austria, 5020
        • Recruiting
        • Universitatsklinik fur Innere Medizin 3
      • Vienna, Austria, 1090
        • Recruiting
        • AKH - Medizinische Universitat Wien
  • Belgium
      • Brussels, Belgium, 1200
        • Recruiting
        • Cliniques Universitaires Sain-Luc
      • Jette, Belgium, 1090
        • Recruiting
        • UZ Brussel
      • Leuven, Belgium, 3000
        • Recruiting
        • UZ Leuven
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Recruiting
        • BC Cancer
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Lady Davis Institute for Medical Research (LDI) Jewish General Hospital (JGH)
  • France
      • Bordeaux, France, 22075
        • Recruiting
        • CHU de Bordeaux - Hôpital Saint André
      • Marseille, France, 13005
        • Recruiting
        • Hopital de la Timone [Recruiting]
      • Paris, France, 75010
        • Recruiting
        • Hopital Saint Lous - APHP
    • Cedex
      • Lyon, Cedex, France, 69373
        • Recruiting
        • Centre Leon Berard
      • Toulouse, Cedex, France, 31059
        • Recruiting
        • Institute Claudius Regaud
      • Villejuif, Cedex, France, 94805
        • Recruiting
        • Institut Gustave Roussy
  • Germany
      • Berlin, Germany, 10115
        • Recruiting
        • Charité - Campus Charité Mitte
      • Dresden, Germany, 01307
        • Recruiting
        • Universitätsklinikum Carl Gustav Carus Dresden
      • Erlangen, Germany, 91054
        • Recruiting
        • Universitaetsklinikum Erlangen
      • Essen, Germany, 45147
        • Recruiting
        • Universitaetsklinikum Essen
      • Hamburg, Germany, 20246
        • Recruiting
        • Universitaetsklinikum Hamburg-Eppendorf
      • Heidelberg, Germany, 69120
        • Recruiting
        • Universitaetsklinikum Heidelberg
      • Kiel, Germany, 24105
        • Recruiting
        • Universitaetsklinikum Schleswig-Holstein
      • Minden, Germany, 32429
        • Recruiting
        • Johannes Wesling Klinikum Minden
      • München, Germany, 80337
        • Recruiting
        • LMU-Campus Innenstadt
      • Tübingen, Germany, 72076
        • Recruiting
        • Universitaetsklinikum Tubingen
    • Kiel
      • Schleswig, Kiel, Germany, 24105
        • Recruiting
        • Universitaetsklinikum Schleswig-Holstein
  • Italy
      • Milan, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Napoli, Italy, 80131
        • Recruiting
        • Instituto Nazionale Tumori Fondazione G. Pascale
      • Perugia, Italy, 6156
        • Recruiting
        • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia
      • Roma, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Siena, Italy, 53100
        • Recruiting
        • A.O.U Senese Policlinico Santa Maria alle Scotte
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Recruiting
        • Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy
      • Gdansk, Poland, 80214
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne (UCK) - Klinika Onkologii i Radioterapii
      • Poznan, Poland, 60355
        • Recruiting
        • Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
      • Warsaw, Poland, 02781
        • Recruiting
        • Narodowy Instytut Onkologii-im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08036
        • Recruiting
        • Hospital Clínico de Barcelona
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28007
        • Recruiting
        • Hospital General Universitario Gregorio Marañon
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Regional Universitario de Málaga
      • Valencia, Spain, 46014
        • Recruiting
        • Hospital General Universitario de Valencia
  • Switzerland
      • Sankt Gallen, Switzerland, 9000
        • Recruiting
        • Kantonsspital St. Gallen
      • Zurich, Switzerland, 8058
        • Recruiting
        • UniversitaetsSpital Zurich
  • United Kingdom
      • Leeds, United Kingdom, LS1 3EX
        • Recruiting
        • Leeds General Infirmary
      • London, United Kingdom, SW3 6JJ
        • Recruiting
        • Royal Marsden Hospital - Chelsea
      • London, United Kingdom, SE1 9RT
        • Recruiting
        • Guys & St Thomas' NHS Foundation Trust
      • London, United Kingdom, SE1 9RT
        • Recruiting
        • Sarah Cannon Research Institute UK
      • Middlesex, United Kingdom, HA6 2RN
        • Recruiting
        • Mount Vernon Cancer Center
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden Hospital - Sutton
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrooke's Hospital
    • England
      • Manchester, England, United Kingdom, M20 4BX
        • Recruiting
        • The Christie NHS Foundation Trust
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2TH
        • Recruiting
        • Queen Elizabeth Hospital
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Arizona
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health Cancer Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute of Emory University
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Cancer Center - Westwood
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • Recruiting
        • St Elizabeth Healthcare (St Elizabeth Medical Center)
      • Edgewood, Kentucky, United States, 41017
        • Recruiting
        • St Elizabeth Healthcare (St Elizabeth Medical
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center (BIDMC)
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota Medical Center
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Minnesota
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
    • New York
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health Cancer Institute - Zuckerberg Cancer Center
      • New York, New York, United States, 10068
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Comprehensive Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • OU Health Stephenson Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Medical Oncology Clinic
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
    • South Carolina
      • Spartanburg, South Carolina, United States, 29303
        • Recruiting
        • Gibbs Cancer Center and Research Institute
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • University of Tennessee Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Hospital/Houston Methodist Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah Huntsman Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • HLA-A*02:01-positive
  • unresectable Stage III or Stage IV non-ocular melanoma
  • archival tumor tissue sample or a newly obtained biopsy of a tumor lesion not previously irradiated has been provided.
  • measurable or non-measurable disease per RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • If applicable, must agree to use highly effective contraception
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent (ICF) and protocol
  • Must agree to provide protocol specified samples for biomarker analyses.

Exclusion Criteria:

  • Pregnant or lactating women
  • diagnosis of ocular or metastatic uveal melanoma
  • history of a malignant disease other than those being treated in this study
  • ineligible to be retreated with pembrolizumab due to a treatment-related AE
  • known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
  • previous severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
  • active autoimmune disease requiring immunosuppressive treatment
  • known psychiatric or substance abuse disorders
  • received prior treatment with a licensed or investigative Immune-mobilizing monoclonal T-cell receptor Against Cancer (ImmTAC) medication or who have not completed adequate washout from prior medications.
  • received chemotherapy or biological cancer therapy (excluding anti-PD(L)1 mAb, ipilimumab, and BRAF TKI regimen) within 14 days of first dose
  • received cellular therapies within 90 days of study intervention
  • ongoing Common Terminology Criteria for Adverse Events(CTCAE) Grade ≥ 2 clinically significant who in the opinion of the investigator could affect the outcome of the study
  • received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of first dose
  • have not progressed on treatment with an anti-PD(L)1 mAb
  • have not received prior treatment with an approved anti-CTLA-4 mAb
  • have a BRAF V600 mutation, who have not received a prior BRAF/MEK TKI regimen
  • currently participating or have participated in a study of an investigational agent or using an investigational device within 30 days of the first dose
  • known history of chronic viral infections such as hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • known clinically significant pulmonary or cardiac disease or impaired lung or cardiac function
  • Out of range Laboratory values
  • history of allogenic tissue/solid organ transplant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Tebentafusp Monotherapy
Participants receive tebentafusp as single agent.
Drug: Tebentafusp
Soluble gp100-specific T cell receptor with anti-CD3 scFV
Experimental: Arm B: Tebentafusp + Pembrolizumab
Participants receive tebentafusp in combination with pembrolizumab.
Drug: Tebentafusp with Pembrolizumab
Soluble gp100-specific T cell receptor with anti-CD3 scFV in combination with pembrolizumab
Experimental: Arm C: Investigator's Choice
Participants receive investigator's choice of therapy.
Drug: Investigators Choice
Investigators choice of therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to ~4 years
OS is the time from randomization to death due to any cause.
Up to ~4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Circulating Tumor DNS (ctDNA)
Time Frame: Up to ~9 weeks
Change from baseline in ctDNA will be assessed.
Up to ~9 weeks
Number of participants with ≥1 adverse event (AE)
Time Frame: Up to ~4 years
Number of participants with AEs.
Up to ~4 years
Number of participants with ≥1 serious adverse event (SAEs)
Time Frame: Up to ~4 years
Number of participants with SAEs.
Up to ~4 years
Number of participants with dose interruptions, reductions, and discontinuations from study therapy due to AEs
Time Frame: Up to ~4 years
Number of participants with tolerability issues.
Up to ~4 years
Number of participants with Grade ≥2 cytokine release syndrome (CRS)
Time Frame: Up to ~4 years
CRS based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
Up to ~4 years
Responses to the EORTC Core Quality of Life (EORTC-QLQ-C30)
Time Frame: At designated time points up to ~4 years
Participant-reported quality of life.
At designated time points up to ~4 years
Responses to the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
Time Frame: At designated time points up to ~4 years
Participant-reported quality of life.
At designated time points up to ~4 years
Plasma Concentration of Tebentafusp
Time Frame: At designated time points up to ~4 years
Plasma concentration of tebentafusp.
At designated time points up to ~4 years
Number of participants with anti-tebentafusp antibodies
Time Frame: At designated time points up to ~4 years
The number of participants with anti drug antibodies (ADA) to tebentafusp.
At designated time points up to ~4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Immunocore Ltd

Investigators

  • Study Director: Mohammed Dar, MD, Immunocore Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 19, 2022

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

August 26, 2022

First Submitted That Met QC Criteria

September 19, 2022

First Posted (Actual)

September 22, 2022

Study Record Updates

Last Update Posted (Actual)

February 25, 2026

Last Update Submitted That Met QC Criteria

February 23, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMCgp100-203

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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