Tebentafusp in Molecular Relapsed Disease (MRD) Melanoma

NCT05315258 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: OCTO_1012019-003946-34
• Study Type: interventional
• Target: 850
• Locations: 1 country
• Sites: 10

Brief Summary

Researchers are trying to find ways to improve the management of people with intermediate or high risk resected cutaneous melanoma or with primary uveal melanoma. This research study is investigating using a new blood test to decide when to give a drug called tebentafusp. Tebentafusp has been used in clinical trials in patients with advanced cutaneous and uveal melanoma. This study is designed to determine if tebentafusp can help patients with cutaneous or uveal melanoma live longer.

Conditions

Melanoma (Skin); Melanoma, Uveal

Keywords

D008545

Outcome Measures

Primary Outcomes (1)

• Estimate the rate of molecular response (MR) to tebentafusp in each of 2 cohorts A. Cutaneous melanoma with MRD B. Uveal melanoma with MRD

  Best response to treatment, with partial molecular response (pMR) defined as a decrease in the allele frequency of the index mutation(s), and complete molecular response (cMR) as no detectable mutation(s)

  ctDNA taken at baseline until end of treatment (maximum of 6 months)

Secondary Outcomes (3)

• Efficacy of tebentafusp

  ctDNA taken at baseline until end of treatment (maximum of 6 months); CT or MRI assessment as per standard of care

• Safety and tolerability of tebentafusp

  Up to 6 months of treatment

• Assess the rate of molecular relapse in; A. Cutaneous melanoma B. Uveal melanoma

  ctDNA taken at baseline and every 3 months during molecular screening

Other Outcomes (2)

• Changes in peripheral T cell populations and in serum cytokines and other analytes

  Up to 6 months of treatment

• Preliminary evaluation of response rate in gp100 expressing melanoma

  ctDNA taken at baseline until end of treatment (maximum of 6 months)

Study Arms (2)

Cutaneous melanoma with molecular relapsed disease

EXPERIMENTAL

tebentafusp weekly IV escalating in the first treatment cycle with dose 20 mcg on day 1, 30 mcg on day 8, 68 mcg on days 15 and 22. Thereafter weekly doses will be 68 mcg IV for 6 months.

Drug: Tebentafusp

Uveal melanoma with molecular relapsed disease

EXPERIMENTAL

tebentafusp weekly IV escalating in the first treatment cycle with dose 20 mcg on day 1, 30 mcg on day 8, 68 mcg on days 15 and 22. Thereafter weekly doses will be 68 mcg IV for 6 months.

Drug: Tebentafusp

Interventions

Tebentafusp DRUG

Tebentafusp supplied as concentrate for solution for infusion and diluted prior to administration. 0.2 mg/mL drug product will be provided as a sterile, refrigerated solution in glass vials.

Also known as: IMCgp100

Cutaneous melanoma with molecular relapsed disease; Uveal melanoma with molecular relapsed disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Uveal or cutaneous melanoma with MRD detected in molecular screening, and repeat confirmation of MRD in the sample taken as part of screening for the main study.
• Written (signed and dated) informed consent.
• Male or female, Age 18 years and above.
• Life expectancy of at least 3 months.
• ECOG performance score of 0 or 1.
• No evidence of metastatic disease on a CT scan of neck/thorax/abdomen/pelvis for cohorts A and B and also on MRI liver for uveal melanoma for cohort B.
• Those receiving prior immunotherapy must have recovered from any immune-mediated adverse events (≤ grade 1) other than endocrinopathies on stable replacement therapy.
• Haematological and biochemical indices within normal ranges (refer to protocol for ranges)

You may not qualify if:

• A patient will not be eligible for tebentafusp administration if any of the following apply:
• Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
• Uveal or cutaneous melanoma patients who present radiologically or clinically detectable disease during screening.
• Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy before Screening is initiated
• Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
• Any other active malignancy, with the exception of malignancies that were treated curatively and have not recurred within 2 years after completion of treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type
• Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV. This study does not require testing to confirm eligibility unless clinically indicated.
• Clinically significant cardiac disease or impaired cardiac function (New York Heart Association grade ≥ 2), including myocardial infarction or unstable angina pectoris within 6 months of screening.
• Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity and any prior immunotherapy approach, 4 weeks is indicated as washout period
• Presence of NCI CTCAE ≥ grade 2 toxicity (except alopecia, peripheral neuropathy, and ototoxicity, which are excluded if ≥ NCI CTCAE grade 3) due to prior cancer therapy.
• Patients currently requiring chronic, systemic corticosteroid therapy at any dose for longer than 2 weeks. Replacement treatment for pituitary or adrenal insufficiency is permitted. Local steroid therapies (e.g. otic, ophthalmic, intra-articular, or inhaled medications) are acceptable.
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. Non-live vaccination (e.g. influenza) are permitted anytime during treatment.
• Major surgery as defined by the investigator within 2 weeks of the first dose of study treatment (minimally invasive procedures such as bronchoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
• Pregnant or lactating women, or women of childbearing potential unless effective methods of contraception are used.
• Women of child-bearing potential who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician.

Sponsors & Collaborators

• University of Oxford: lead
• Immunocore Ltd: collaborator

Study Sites (10)

Cambridge University Hospitals NHS Foundation Trust (Screening only)

Cambridge, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

The Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

The Christie Hospital

Manchester, United Kingdom

Location

Mount Vernon Cancer Centre

Middlesex, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom

Location

Churchill Hospital, Oxford University Hospitals NHS Trust

Oxford, OX3 7LE, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust (Screening only)

Sheffield, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

tebentafusp

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Study Officials

• Mark Middleton

  Consultant Medical Oncologist and Professor of Experimental Cancer Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2021
• First Posted: April 7, 2022
• Study Start: July 25, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (10)