Advanced Melanoma
Conditions
Keywords
Melanoma, IMCgp100, Tebentafusp, Cutaneous Melanoma, Immunotherapy, gp100, TCR, Pembrolizumab, 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, checkpoint therapy
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.
Interventions
DRUGTebentafusp
Soluble gp100-specific T cell receptor with anti-CD3 scFV
DRUGTebentafusp with Pembrolizumab
Soluble gp100-specific T cell receptor with anti-CD3 scFV in combination with pembrolizumab
DRUGInvestigators Choice
Investigators choice of therapy
Sponsors
Immunocore Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to ~4 years | OS is the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
CONTACTImmunocore Medical Information
CONTACTImmunocore Medical Information EU
Outcome results
None listed