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

Immunocore

Status and phase: Enrolling; Phase 3

Conditions: Advanced Melanoma

Treatments: Drug: Tebentafusp with Pembrolizumab; Drug: Tebentafusp; Drug: Investigators Choice

Study type: Interventional

Funder types: Industry

Identifiers

NCT05549297

IMCgp100-203

Details and patient eligibility

About

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.

Full 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.

Enrollment: 540 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 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)
• Out of range Laboratory values
• history of allogenic tissue/solid organ transplant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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540 participants in 3 patient groups

Arm A: Tebentafusp Monotherapy

Experimental group

Description:

Participants receive tebentafusp as single agent.

Treatment:

Drug: Tebentafusp

Arm B: Tebentafusp + Pembrolizumab

Experimental group

Description:

Participants receive tebentafusp in combination with pembrolizumab.

Treatment:

Drug: Tebentafusp with Pembrolizumab

Arm C: Investigator's Choice

Experimental group

Description:

Participants receive investigator's choice of therapy.

Treatment:

Drug: Investigators Choice