Using tebentafusp for melanoma with molecular relapsed disease

A Phase II Non-Randomized, Open-label, Multi-centre Study of the Safety and Efficacy of Tebentafusp in Melanoma With Molecular Relapsed Disease

This study is testing if the drug tebentafusp can help patients with melanoma that has come back at a molecular level after surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 850 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Oxford (other)
• Drugs / interventions: immunotherapy
• Locations: 10 sites (Cambridge and 9 other locations)
• Trial ID: NCT05315258 on ClinicalTrials.gov

What this trial studies

This research investigates the use of tebentafusp, a drug previously tested in advanced melanoma, for patients with intermediate or high-risk resected cutaneous melanoma or primary uveal melanoma who have molecular relapsed disease (MRD). The study involves two cohorts: one for cutaneous melanoma and another for uveal melanoma, with approximately 850 patients enrolled across 50 centers. Patients will undergo screening for HLA-A*0201 status and, if positive for MRD, will receive tebentafusp treatment for up to six months, followed by a 12-month follow-up for relapse monitoring.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with cutaneous or uveal melanoma and confirmed MRD.

Not a fit: Patients with metastatic disease or those who do not have HLA-A*0201 status will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with melanoma who have MRD.

How similar studies have performed: Previous studies have shown promise with tebentafusp in advanced melanoma, suggesting potential for success in this new application.

Eligibility criteria

Inclusion Criteria:

A patient will be eligible for inclusion in cohort A or B if all of the following criteria apply:

1. 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.
2. Written (signed and dated) informed consent.
3. Male or female, Age 18 years and above.
4. Life expectancy of at least 3 months.
5. ECOG performance score of 0 or 1.
6. 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.
7. Those receiving prior immunotherapy must have recovered from any immune-mediated adverse events (≤ grade 1) other than endocrinopathies on stable replacement therapy.
8. Haematological and biochemical indices within normal ranges (refer to protocol for ranges)

Exclusion Criteria:

A patient will not be eligible for tebentafusp administration if any of the following apply:

1. Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment.
2. Uveal or cutaneous melanoma patients who present radiologically or clinically detectable disease during screening.
3. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy before Screening is initiated
4. 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.
5. 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
6. 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.
7. 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.
8. Active autoimmune disease or a documented history of autoimmune disease within 3 years of screening (diabetes mellitus, vitiligo, managed hypothyroidism, psoriasis and managed asthma are not exclusions).
9. 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
10. 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.
11. 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.
12. 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.
13. 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).
14. Pregnant or lactating women, or women of childbearing potential unless effective methods of contraception are used.
15. 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.
16. Male patients must be surgically sterile or use double barrier contraception method from enrolment through treatment and for 6 months following administration of the last dose of study drug.

Where this trial is running

Cambridge and 9 other locations

• Cambridge University Hospitals NHS Foundation Trust (Screening only) — Cambridge, United Kingdom (RECRUITING)
• The Beatson West of Scotland Cancer Centre — Glasgow, United Kingdom (RECRUITING)
• The Clatterbridge Cancer Centre — Liverpool, United Kingdom (RECRUITING)
• University College London Hospital — London, United Kingdom (RECRUITING)
• The Christie Hospital — Manchester, United Kingdom (RECRUITING)
• Mount Vernon Cancer Centre — Middlesex, United Kingdom (RECRUITING)
• Newcastle upon Tyne Hospitals NHS Foundation Trust — Newcastle, United Kingdom (RECRUITING)
• Churchill Hospital, Oxford University Hospitals NHS Trust — Oxford, United Kingdom (RECRUITING)
• Sheffield Teaching Hospitals NHS Foundation Trust (Screening only) — Sheffield, United Kingdom (RECRUITING)
• University Hospital Southampton NHS Foundation Trust — Southampton, United Kingdom (RECRUITING)

Study contacts

• Principal investigator: Mark Middleton — Consultant Medical Oncologist and Professor of Experimental Cancer Medicine
• Study coordinator: Lisa Poulton

Conditions: Melanoma, Melanoma, Uveal, D008545