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

Phase 3

Recruiting

• Conditions: Advanced Melanoma
• Interventions: Drug: Tebentafusp; Drug: Tebentafusp with Pembrolizumab; Drug: Investigators Choice

• 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.

Study Timeline

• Study First Submitted: 2022-08-26
• Study First Submitted QC: 2022-09-19
• Study First Posted: 2022-09-22
• Study Start: 2022-12-19
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-22
• Last Update Posted: 2025-07-23
• Primary Completion: 2028-03
• Study Completion: 2028-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 540

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

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.

Trial Locations

Locations (70)

Winship Cancer Institute of Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Kansas Cancer Center - Westwood; 🇺🇸 Westwood, Kansas, United States

LKH - Universitaetsklinikum Graz; 🇦🇹 Graz, Austria

Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Guys & St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom

Sarah Cannon Research Institute UK; 🇬🇧 London, United Kingdom

Mayo Clinic Arizona; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

Orlando Health Cancer Institute; 🇺🇸 Orlando, Florida, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

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