Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)
- Conditions
- Advanced Melanoma
- Interventions
- Registration Number
- NCT05549297
- Lead Sponsor
- Immunocore Ltd
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 540
- 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.
- 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
- clinically significant cardiac or pulmonary disease or impaired cardiac function
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Tebentafusp Monotherapy Tebentafusp Participants receive tebentafusp as single agent. Arm B: Tebentafusp + Pembrolizumab Tebentafusp with Pembrolizumab Participants receive tebentafusp in combination with pembrolizumab. Arm C: Investigator's Choice Investigators Choice Participants receive investigator's choice of therapy.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to ~4 years OS is the time from randomization to death due to any cause.
- Secondary Outcome Measures
Name Time Method Change from Baseline in Circulating Tumor DNS (ctDNA) Up to ~9 weeks Change from baseline in ctDNA will be assessed.
Number of participants with ≥1 adverse event (AE) Up to ~4 years Number of participants with AEs.
Number of participants with ≥1 serious adverse event (SAEs) Up to ~4 years Number of participants with SAEs.
Number of participants with dose interruptions, reductions, and discontinuations from study therapy due to AEs Up to ~4 years Number of participants with tolerability issues.
Number of participants with Grade ≥2 cytokine release syndrome (CRS) Up to ~4 years CRS based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
Responses to the EORTC Core Quality of Life (EORTC-QLQ-C30) At designated time points up to ~4 years Participant-reported quality of life.
Responses to the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) At designated time points up to ~4 years Participant-reported quality of life.
Plasma Concentration of Tebentafusp At designated time points up to ~4 years Plasma concentration of tebentafusp.
Number of participants with anti-tebentafusp antibodies At designated time points up to ~4 years The number of participants with anti drug antibodies (ADA) to tebentafusp.
Related Research Topics
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Trial Locations
- Locations (64)
University of Utah Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Charité - Campus Charité Mitte
🇩🇪Berlin, Germany
Universitaetsklinikum Erlangen
🇩🇪Erlangen, Germany
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Thomas Jefferson University Medical Oncology Clinic
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
Mayo Clinic Minnesota
🇺🇸Rochester, Minnesota, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Northwell Health Cancer Institute - Zuckerberg Cancer Center
🇺🇸Lake Success, New York, United States
Houston Methodist Hospital/Houston Methodist Cancer Center
🇺🇸Houston, Texas, United States
Melanoma Institute Australia
🇦🇺Wollstonecraft, New South Wales, Australia
Universitatsklinik fur Innere Medizin 3
🇦🇹Salzburg, Austria
AKH - Medizinische Universität Wien
🇦🇹Wien, Austria
Gallipoli Medical Research Foundation (GMRF)
🇦🇺Greenslopes, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
Kepler Universitätsklinikum
🇦🇹Linz, Austria
Cliniques Universitaires Sain-Luc
🇧🇪Bruxelles, Belgium
UZ Brussel
🇧🇪Jette, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Centre Leon Berard
🇫🇷Lyon, Cedex, France
Institute Claudius Regaud
🇫🇷Toulouse, Cedex, France
Institut Gustave Roussy
🇫🇷Villejuif, Cedex, France
CHU de Bordeaux - Hopital Saint Andre
🇫🇷Bordeaux, France
Hopital de la Timone [Recruiting]
🇫🇷Marseille, France
Hopital Saint Lous - APHP
🇫🇷Paris, France
Universitaetsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Universitatsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
LMU-Campus Innenstadt
🇩🇪Muenchen, Germany
Universitaetsklinikum Tübingen
🇩🇪Tübingen, Germany
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Instituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy
Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
🇵🇱Poznań, Poland
Narodowy Instytut Onkologii-im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
🇵🇱Warsaw, Poland
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinico de Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
A.O.U Senese Policlinico Santa Maria alle Scotte
🇮🇹Siena, Italy
Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy
🇵🇱Bydgoszcz, Poland
Uniwersyteckie Centrum Kliniczne (UCK) - Klinika Onkologii i Radioterapii
🇵🇱Gdańsk, Poland
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Kantonsspital St. Gallen
🇨🇭Saint Gallen, Switzerland
Universitaetsspital Zurich
🇨🇭Zürich, Switzerland
Addenbrooke's Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, West Midlands, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
Royal Marsden Hospital - Chelsea
🇬🇧London, United Kingdom
Mount Vernon Cancer Center
🇬🇧Middlesex, United Kingdom
Royal Marsden Hospital - Sutton
🇬🇧Sutton, United Kingdom