Clinical trial NCT05549297: Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Melanoma
Keywords: Melanoma
IMCgp100
Tebentafusp
Cutaneous Melanoma
Immunotherapy
gp100
TCR
Pembrolizumab
Bispecific T cell receptor fusion protein
ImmTAC (Immune-mobilizing monoclonal T-cell receptor Against Cancer)
Immune mobilizing monoclonal T cell receptor against cancer
KIMMTRAK
Acral Melanoma
Mucosal Melanoma
Blue Nevus
anti-PDL1
checkpoint therapy
Lead sponsor: Immunocore Ltd
Sponsor class: INDUSTRY
First posted: 2022-09-22
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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
* 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to ~4 years
Secondary outcomes:
measure: Change from Baseline in Circulating Tumor DNS (ctDNA)
timeFrame: Up to ~9 weeks
measure: Number of participants with ≥1 adverse event (AE)
timeFrame: Up to ~4 years
measure: Number of participants with ≥1 serious adverse event (SAEs)
timeFrame: Up to ~4 years
measure: Number of participants with dose interruptions, reductions, and discontinuations from study therapy due to AEs
timeFrame: Up to ~4 years
measure: Number of participants with Grade ≥2 cytokine release syndrome (CRS)
timeFrame: Up to ~4 years
measure: Responses to the EORTC Core Quality of Life (EORTC-QLQ-C30)
timeFrame: At designated time points up to ~4 years
measure: Responses to the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
timeFrame: At designated time points up to ~4 years
measure: Plasma Concentration of Tebentafusp
timeFrame: At designated time points up to ~4 years
measure: Number of participants with anti-tebentafusp antibodies
timeFrame: At designated time points up to ~4 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Minnesota
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute - Zuckerberg Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University Medical Oncology Clinic
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital/Houston Methodist Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Foundation (GMRF)
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitätsklinikum
city: Salzburg
country: Austria
facility: Universitatsklinik fur Innere Medizin 3
city: Wien
country: Austria
facility: AKH - Medizinische Universität Wien
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Sain-Luc
city: Jette
country: Belgium
facility: UZ Brussel
city: Leuven
country: Belgium
facility: UZ Leuven
city: Lyon
country: France
facility: Centre Leon Berard
state: Cedex
city: Toulouse
country: France
facility: Institute Claudius Regaud
state: Cedex
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Cedex
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hopital Saint Andre
city: Marseille
country: France
facility: Hopital de la Timone [Recruiting]
city: Paris
country: France
facility: Hopital Saint Lous - APHP
city: Schleswig
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
state: Kiel
city: Berlin
country: Germany
facility: Charité - Campus Charité Mitte
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus Dresden
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: Muenchen
country: Germany
facility: LMU-Campus Innenstadt
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tübingen
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Instituto Nazionale Tumori Fondazione G. Pascale
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Siena
country: Italy
facility: A.O.U Senese Policlinico Santa Maria alle Scotte
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne (UCK) - Klinika Onkologii i Radioterapii
city: Poznań
country: Poland
facility: Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii-im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinico de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: Universitaetsspital Zurich
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: Cambridgeshire
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
state: West Midlands
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Chelsea
city: Middlesex
country: United Kingdom
facility: Mount Vernon Cancer Center
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - Sutton
Study officials:
References: