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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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)

Conditions
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Advanced Melanoma

Intervention / Treatment
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* Drug: Tebentafusp
* Drug: Tebentafusp with Pembrolizumab
* Drug: Investigators Choice


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Tebentafusp as single agent | Drug: Tebentafusp<br>* soluble gp100-specific T cell receptor with anti-CD3 scFV<br>|
| Experimental: Arm B<br>Tebentafusp in combination with Pembrolizumab | Drug: Tebentafusp with Pembrolizumab<br>* soluble gp100-specific T cell receptor with anti-CD3 scFV in combination with Pembrolizumab<br>|
| Experimental: Arm C<br>Straight to on protocol survival follow up including investigators choice of therapy | Drug: Investigators Choice<br>* Investigators choice of therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2 Primary | ctDNA reduction on treatment relative to baseline | from randomization to approximately 9 weeks | 
| Phase 2 Primary | Overall Survival | from randomization to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Safety: Tolerability | Dose Interruptions and discontinuations; Dose Reductions | from first dose to approximately 2 years | 
| Serum Pharmacokinetics | Tebentafusp concentration. Tebentafusp PK parameters (eg, Cmax, Tmax, Cavg, t1/2) | from first dose to approximately 2 years | 
| Phase 2 Secondary | Incidence of anti-tebentafusp antibodies | from first dose to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, checkpoint therapy, TCR, 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, IMCgp100, Tebentafusp, Cutaneous Melanoma, Immunotherapy, gp100, Pembrolizumab