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

Advanced Melanoma Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05549297
• Other study ID #: IMCgp100-203
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 19, 2022
• Est. completion date: September 2027

Study information

• Verified date: March 2024
• Source: Immunocore Ltd
• Contact: Immunocore Medical Information
• Phone: 844-466-8661
• Email: medical.information[@]immunocore.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy and safety of tebentafusp-based regimens 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

Description:

This is a Phase 2/3, 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 prior ipilimumab and, if the participant has a BRAF mutation, a prior BRAF tyrosine kinase inhibitor (TKI) regimen.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 460
• Est. completion date: September 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 with clinically significant cardiac 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 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 ipilimumab
• 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)
• Out of range Laboratory values
• history of allogenic tissue/solid organ transplant

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma

Intervention

Drug:
• Tebentafusp
soluble gp100-specific T cell receptor with anti-CD3 scFV
• Tebentafusp with Pembrolizumab
soluble gp100-specific T cell receptor with anti-CD3 scFV in combination with Pembrolizumab
• Investigators Choice
Investigators choice of therapy

Locations

Country	Name	City	State
Australia	Gallipoli Medical Research Foundation (GMRF)	Greenslopes	Queensland
Australia	Alfred Health	Melbourne	Victoria
Australia	Melanoma Institute Australia	Wollstonecraft	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	LKH - Universitaetsklinikum Graz	Graz
Austria	Kepler Universitätsklinikum	Linz
Austria	Universitatsklinik fur Innere Medizin 3	Salzburg
Austria	AKH - Medizinische Universität Wien	Wien
Belgium	Cliniques Universitaires Sain-Luc	Bruxelles
Belgium	UZ Brussel	Jette
Belgium	UZ Leuven	Leuven
France	CHU de Bordeaux - Hopital Saint Andre	Bordeaux
France	Centre Leon Berard	Lyon	Cedex
France	Hopital de la Timone [Recruiting]	Marseille
France	Hopital Saint Lous - APHP	Paris
France	Institute Claudius Regaud	Toulouse	Cedex
France	Institut Gustave Roussy	Villejuif	Cedex
Germany	Klinische Studien Hauttumorcentrum	Berlin
Germany	Universitatsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Onkologische Studienxentrale Houtklinik Erlangen	Erlangen
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Schleswig-Holstein	Kiel
Germany	Johannes Wesling Klinikum Minden	Minden
Germany	LMU-Campus Innenstadt	Munich
Germany	Universitaetsklinikum Schleswig-Holstein	Schleswig	Kiel
Germany	Universitaetsklinikum Tübingen	Tübingen
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Instituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Italy, Perugia Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia	Perugia
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	A.O.U Senese Policlinico Santa Maria alle Scotte	Siena
Poland	Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne (UCK) - Klinika Onkologii i Radioterapii	Gdansk
Poland	Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu	Poznan
Poland	Narodowy Instytut Onkologii-im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warsaw
Spain	Hospital Clinico de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Hospital General Universitario de Valencia	Valencia
Switzerland	Kantonsspital St. Gallen	Saint Gallen
Switzerland	Universitaetsspital Zurich	Zürich
United Kingdom	Queen Elizabeth Hospital	Birmingham	West Midlands
United Kingdom	Addenbrooke's Hospital	Cambridge	Cambridgeshire
United Kingdom	Guy's & St Thomas' NHS Foundation Trust	Lambeth	Greater London
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Barts Hospital	London
United Kingdom	Royal Marsden Hospital - Chelsea	London
United Kingdom	Mount Vernon Cancer Center	Middlesex
United Kingdom	Royal Marsden Hospital - Sutton	Sutton
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Houston Methodist Hospital/Houston Methodist Cancer Center	Houston	Texas
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	University of Minnesota Medical Center - Masonic Cancer Center	Minneapolis	Minnesota
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	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Thomas Jefferson University Medical Oncology Clinic	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic Minnesota	Rochester	Minnesota
United States	University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah
United States	Gibbs Cancer Center and Research Institute	Spartanburg	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Immunocore Ltd

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  Germany,  Italy,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 2 Primary	ctDNA reduction on treatment relative to baseline	from randomization to approximately 9 weeks
Primary	Phase 2 Primary	Overall Survival	from randomization to approximately 2 years
Secondary	Safety: Adverse Events and Severe Adverse Events	Incidence and severity of AEs, SAEs and changes from baseline in laboratory parameters, vital signs, and ECGs	from first dose to approximately 2 years
Secondary	Safety: Tolerability	Dose Interruptions and discontinuations; Dose Reductions	from first dose to approximately 2 years
Secondary	Serum Pharmacokinetics	Tebentafusp concentration. Tebentafusp PK parameters (eg, Cmax, Tmax, Cavg, t1/2)	from first dose to approximately 2 years
Secondary	Phase 2 Secondary	Incidence of anti-tebentafusp antibodies	from first dose to approximately 2 years