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

Sponsor

Immunocore Ltd (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05549297

Collaborator

(none)

460

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Advanced Melanoma	Drug: Tebentafusp Drug: Tebentafusp with Pembrolizumab Drug: Investigators Choice	Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

460 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Arm A

Tebentafusp as single agent

Drug: Tebentafusp

soluble gp100-specific T cell receptor with anti-CD3 scFV

Experimental: Arm B

Tebentafusp in combination with Pembrolizumab

Drug: Tebentafusp with Pembrolizumab

soluble gp100-specific T cell receptor with anti-CD3 scFV in combination with Pembrolizumab

Experimental: Arm C

Straight to on protocol survival follow up including investigators choice of therapy

Drug: Investigators Choice

Investigators choice of therapy

Outcome Measures

Primary Outcome Measures

Phase 2 Primary [from randomization to approximately 9 weeks]
ctDNA reduction on treatment relative to baseline
Phase 2 Primary [from randomization to approximately 2 years]
Overall Survival

Secondary Outcome Measures

Safety: Adverse Events and Severe Adverse Events [from first dose to approximately 2 years]
Incidence and severity of AEs, SAEs and changes from baseline in laboratory parameters, vital signs, and ECGs
Safety: Tolerability [from first dose to approximately 2 years]
Dose Interruptions and discontinuations
Safety: Tolerability [from first dose to approximately 2 years]
Dose Reductions
Serum Pharmacokinetics [from first dose to approximately 2 years]
Tebentafusp concentration. Tmax: The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
Phase 2 Secondary [from first dose to approximately 2 years]
Incidence of anti-tebentafusp antibodies
Efficacy: Disease Control Rate [from first dose to approximately 3 weeks]
Incidence of Grade ≥ 2 Cytokine Release Syndrome based on ASTCT grade
Efficacy: Disease Control Rate [from first dose to approximately 3 weeks]
time to onset of CRS component event
Efficacy: Disease Control Rate [from first dose to approximately 3 weeks]
duration of defined CRS component events
Efficacy: Disease Control Rate [from first dose to approximately 3 weeks]
incidence of prolonged hospitalization during the first 3 weeks of dosing

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

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 medical condition
known psychiatric or substance abuse disorders
received prior treatment with a licensed or investigative Immune-mobilizing monoclonal T-cell receptor Against Cancer (ImmTAC) medication
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 first dose
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
Out of range Laboratory values
history of allogenic tissue/solid organ transplant