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)

Overview

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.

Interventions

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

Primary outcome measures

• Overall Survival (OS) [Time frame: Up to ~4 years]

Secondary outcome measures (9)

• Change from Baseline in Circulating Tumor DNS (ctDNA) [Time frame: Up to ~9 weeks]
• Number of participants with ≥1 adverse event (AE) [Time frame: Up to ~4 years]
• Number of participants with ≥1 serious adverse event (SAEs) [Time frame: 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 Grade ≥2 cytokine release syndrome (CRS) [Time frame: 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]
• 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]
• Plasma Concentration of Tebentafusp [Time frame: 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]

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
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 25 centers

• Mayo Clinic Arizona — Phoenix
• Mayo Clinic Florida — Jacksonville
• Orlando Health Cancer Institute — Orlando
• Winship Cancer Institute of Emory University — Atlanta
• University of Kansas Cancer Center - Westwood — Westwood
• St Elizabeth Healthcare (St Elizabeth Medical Center) — Edgewood
• St Elizabeth Healthcare (St Elizabeth Medical — Edgewood
• Massachusetts General Hospital — Boston
• … and 17 more centers

Germany · 11 centers

• Universitaetsklinikum Schleswig-Holstein — Schleswig
• Charité - Campus Charité Mitte — Berlin
• Universitatsklinikum Carl Gustav Carus Dresden — Dresden
• Universitaetsklinikum Erlangen — Erlangen
• Universitaetsklinikum Essen — Essen
• Universitaetsklinikum Hamburg-Eppendorf — Hamburg
• Universitaetsklinikum Heidelberg — Heidelberg
• Universitaetsklinikum Schleswig-Holstein — Kiel
• … and 3 more centers

United Kingdom · 9 centers

• Addenbrooke's Hospital — Cambridge
• The Christie NHS Foundation Trust — Manchester
• Queen Elizabeth Hospital — Birmingham
• Leeds General Infirmary — Leeds
• Guys & St Thomas' NHS Foundation Trust — London
• Sarah Cannon Research Institute UK — London
• Royal Marsden Hospital - Chelsea — London
• … and 2 more centers

France · 6 centers

• Centre Leon Berard — Lyon
• Institute Claudius Regaud — Toulouse
• Institut Gustave Roussy — Villejuif
• CHU de Bordeaux - Hopital Saint Andre — Bordeaux
• Hopital de la Timone [Recruiting] — Marseille
• Hopital Saint Lous - APHP — Paris

Spain · 6 centers

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Clinico de Barcelona — Barcelona
• Hospital General Universitario Gregorio Marañon — Madrid
• Hospital Universitario Ramon y Cajal — Madrid
• Hospital Regional Universitario de Malaga — Málaga
• Hospital General Universitario de Valencia — Valencia

Italy · 5 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• Instituto Nazionale Tumori Fondazione G. Pascale — Naples
• Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia — Perugia
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• A.O.U Senese Policlinico Santa Maria alle Scotte — Siena

Australia · 4 centers

• Melanoma Institute Australia — Wollstonecraft
• Gallipoli Medical Research Foundation (GMRF) — Greenslopes
• Princess Alexandra Hospital — Woolloongabba
• Alfred Health — Melbourne

Austria · 4 centers

• LKH - Universitaetsklinikum Graz — Graz
• Kepler Universitätsklinikum — Linz
• Universitatsklinik fur Innere Medizin 3 — Salzburg
• AKH - Medizinische Universität Wien — Vienna

Poland · 4 centers

• Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy — Bydgoszcz
• Uniwersyteckie Centrum Kliniczne (UCK) - Klinika Onkologii i Radioterapii — Gdansk
• Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego — Poznan
• Narodowy Instytut Onkologii-im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy — Warsaw

Belgium · 3 centers

• Cliniques Universitaires Sain-Luc — Brussels
• UZ Brussel — Jette
• UZ Leuven — Leuven

Canada · 3 centers

• BC Cancer — Vancouver
• Princess Margaret Hospital — Toronto
• Lady Davis Institute for Medical Research (LDI) Jewish General Hospital (JGH) — Montreal

Switzerland · 2 centers

• Kantonsspital St. Gallen — Sankt Gallen
• Universitaetsspital Zurich — Zurich

Identifiers

NCT: NCT05549297 · IMCgp100-203

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗