NCT05549297

Brief Summary

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.

Trial Health

88
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
540

participants targeted

Target at P75+ for phase_3

Timeline
26mo left

Started Dec 2022

Longer than P75 for phase_3

Geographic Reach
11 countries

78 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress61%
Dec 2022Jul 2028

First Submitted

Initial submission to the registry

August 26, 2022

Completed
27 days until next milestone

First Posted

Study publicly available on registry

September 22, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

December 19, 2022

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2028

Last Updated

February 25, 2026

Status Verified

February 1, 2026

Enrollment Period

5.2 years

First QC Date

August 26, 2022

Last Update Submit

February 23, 2026

Conditions

Keywords

MelanomaIMCgp100TebentafuspCutaneous MelanomaImmunotherapygp100TCRPembrolizumabBispecific T cell receptor fusion proteinImmTAC (Immune-mobilizing monoclonal T-cell receptor Against Cancer)Immune mobilizing monoclonal T cell receptor against cancerKIMMTRAKAcral MelanomaMucosal MelanomaBlue Nevusanti-PDL1checkpoint therapy

Outcome Measures

Primary Outcomes (1)

  • Overall Survival (OS)

    OS is the time from randomization to death due to any cause.

    Up to ~4 years

Secondary Outcomes (9)

  • Change from Baseline in Circulating Tumor DNS (ctDNA)

    Up to ~9 weeks

  • Number of participants with ≥1 adverse event (AE)

    Up to ~4 years

  • Number of participants with ≥1 serious adverse event (SAEs)

    Up to ~4 years

  • Number of participants with dose interruptions, reductions, and discontinuations from study therapy due to AEs

    Up to ~4 years

  • Number of participants with Grade ≥2 cytokine release syndrome (CRS)

    Up to ~4 years

  • +4 more secondary outcomes

Study Arms (3)

Arm A: Tebentafusp Monotherapy

EXPERIMENTAL

Participants receive tebentafusp as single agent.

Drug: Tebentafusp

Arm B: Tebentafusp + Pembrolizumab

EXPERIMENTAL

Participants receive tebentafusp in combination with pembrolizumab.

Drug: Tebentafusp with Pembrolizumab

Arm C: Investigator's Choice

EXPERIMENTAL

Participants receive investigator's choice of therapy.

Drug: Investigators Choice

Interventions

Soluble gp100-specific T cell receptor with anti-CD3 scFV

Arm A: Tebentafusp Monotherapy

Soluble gp100-specific T cell receptor with anti-CD3 scFV in combination with pembrolizumab

Arm B: Tebentafusp + Pembrolizumab

Investigators choice of therapy

Arm C: Investigator's Choice

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (82)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Kansas Cancer Center - Westwood

Westwood, Kansas, 66205, United States

RECRUITING

St Elizabeth Healthcare (St Elizabeth Medical Center)

Edgewood, Kentucky, 41017, United States

RECRUITING

St Elizabeth Healthcare (St Elizabeth Medical

Edgewood, Kentucky, 41017, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic Minnesota

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

RECRUITING

Northwell Health Cancer Institute - Zuckerberg Cancer Center

Lake Success, New York, 11042, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10068, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Thomas Jefferson University Medical Oncology Clinic

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Gibbs Cancer Center and Research Institute

Spartanburg, South Carolina, 29303, United States

RECRUITING

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

RECRUITING

Houston Methodist Hospital/Houston Methodist Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

Gallipoli Medical Research Foundation (GMRF)

Greenslopes, Queensland, 4120, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

Alfred Health

Melbourne, Victoria, 3004, Australia

RECRUITING

LKH - Universitaetsklinikum Graz

Graz, 8036, Austria

RECRUITING

Kepler Universitätsklinikum

Linz, 4020, Austria

RECRUITING

Universitatsklinik fur Innere Medizin 3

Salzburg, 5020, Austria

RECRUITING

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

RECRUITING

Cliniques Universitaires Sain-Luc

Brussels, 1200, Belgium

RECRUITING

UZ Brussel

Jette, 1090, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

BC Cancer

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Lady Davis Institute for Medical Research (LDI) Jewish General Hospital (JGH)

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Centre Leon Berard

Lyon, Cedex, 69373, France

RECRUITING

Institute Claudius Regaud

Toulouse, Cedex, 31059, France

RECRUITING

Institut Gustave Roussy

Villejuif, Cedex, 94805, France

RECRUITING

CHU de Bordeaux - Hopital Saint Andre

Bordeaux, 22075, France

RECRUITING

Hopital de la Timone [Recruiting]

Marseille, 13005, France

RECRUITING

Hopital Saint Lous - APHP

Paris, 75010, France

RECRUITING

Universitaetsklinikum Schleswig-Holstein

Schleswig, Kiel, 24105, Germany

RECRUITING

Charité - Campus Charité Mitte

Berlin, 10115, Germany

RECRUITING

Universitatsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

RECRUITING

Universitaetsklinikum Erlangen

Erlangen, 91054, Germany

RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

RECRUITING

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitaetsklinikum Schleswig-Holstein

Kiel, 24105, Germany

RECRUITING

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

RECRUITING

LMU-Campus Innenstadt

München, 80337, Germany

RECRUITING

Universitaetsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Instituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131, Italy

RECRUITING

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, 6156, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

A.O.U Senese Policlinico Santa Maria alle Scotte

Siena, 53100, Italy

RECRUITING

Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy

Bydgoszcz, 85-796, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne (UCK) - Klinika Onkologii i Radioterapii

Gdansk, 80214, Poland

RECRUITING

Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu

Poznan, 60355, Poland

RECRUITING

Narodowy Instytut Onkologii-im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, 02781, Poland

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Clinico de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

RECRUITING

Hospital General Universitario de Valencia

Valencia, 46014, Spain

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, 9000, Switzerland

RECRUITING

Universitaetsspital Zurich

Zurich, 8058, Switzerland

RECRUITING

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

RECRUITING

Queen Elizabeth Hospital

Birmingham, West Midlands, B15 2TH, United Kingdom

RECRUITING

Leeds General Infirmary

Leeds, LS1 3EX, United Kingdom

RECRUITING

Guys & St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

Sarah Cannon Research Institute UK

London, SE1 9RT, United Kingdom

RECRUITING

Royal Marsden Hospital - Chelsea

London, SW3 6JJ, United Kingdom

RECRUITING

Mount Vernon Cancer Center

Middlesex, HA6 2RN, United Kingdom

RECRUITING

Royal Marsden Hospital - Sutton

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

MelanomaNevus, Blue

Interventions

tebentafusppembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue DiseasesNevus, PigmentedNevus

Central Study Contacts

Immunocore Medical Information

CONTACT

Immunocore Medical Information EU

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 26, 2022

First Posted

September 22, 2022

Study Start

December 19, 2022

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

July 1, 2028

Last Updated

February 25, 2026

Record last verified: 2026-02

Locations