Adjuvant Tebentafusp in High Risk Ocular Melanoma

NCT06246149 | Recruiting Phase 3 DMC

• 2 other identifiers: EORTC-2022-MGEU trial number
• Study Type: interventional
• Target: 290
• Locations: 9 countries
• Sites: 15

Brief Summary

At least 50% of patients with high-risk primary uveal melanoma will develop a recurrence following treatment of the primary tumour. Observation is currently the standard of care in the non-metastatic setting. Tebentafusp is the first agent proven to improve overall survival in patients with metastatic uveal melanoma in a randomized trial. Based on the results in the advanced setting, it is hypothesized that treatment with tebentafusp may reduce the risk of development of disease recurrence.

Conditions

Uveal Melanoma

Keywords

Tebentafusp; Adjuvant setting; Randomized phase III study; non-metastatic uveal melanoma

Outcome Measures

Primary Outcomes (1)

• Recurrence-Free survival (RFS)

  RFS is defined as the time between randomization and local recurrence, distant recurrence, or death, whichever occurs first

  8.1 years from first patient in

Secondary Outcomes (3)

• Overall Survival (OS)

  8.1 years from first patient in

• Occurrence of Adverse Events

  8.1 years from first patient in

• Health-related Quality of Life

  8.1 years from first patient in

Study Arms (2)

Tebentafusp

EXPERIMENTAL

Participants will receive tebentafusp 20 mcg on week 1, 30 mcg on week 2, 68 mcg on week 3, and 68 mcg weekly thereafter for 6 months i.e., maximum 26 infusions.

Drug: Tebentafusp

Observation

NO INTERVENTION

Interventions

Tebentafusp DRUG

Tebentafusp will be administered weekly i.v.

Tebentafusp

Eligibility Criteria

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

You may qualify if:

• Primary non-metastatic UM, except iris melanoma, after definitive treatment either by surgery or radiotherapy
• Time from primary treatment smaller than 11 weeks (note that the maximum time between primary treatment and randomization is 12 weeks )
• High-risk according to either 1) clinical criteria: TNM (AJCC8) stage III or 2) genetic criteria: monosomy 3 or GEP class 2. Prior to enrolment of the first patient, each site will declare which of the two genetic criteria it uses. Patients with stage I and stage II are only eligible if they meet the genetic criterion declared by the site.
• ECOG performance status of 0 or 1
• years or older
• HLA-A\*02:01 positivity by local assessment
• No evidence of UM recurrence, as evidenced by the required baseline imaging performed within 4 weeks prior to randomization
• Adequate organ function
• Time-interval between the end of primary treatment and the randomization less than or equal to 12 weeks
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for women of childbearing potential (WOCBP) within 3 days prior to randomization.
• For patients of childbearing / reproductive potential, agreement to use adequate birth control measures during the study treatment period and for at least 6 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
• For female subjects who are breast feeding, agreement to discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
• Written informed consent according to ICH/GCP and local regulations

You may not qualify if:

• Clinically significant cardiac disease or impaired cardiac function, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association grade ≥ 2), uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment
• QTcF \> 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome based on at least 3 ECGs obtained over a brief time interval (i.e., within 30 minutes)
• Acute myocardial infarction or unstable angina pectoris \< 6 months prior to screening
• Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to randomization
• Any evidence of severe or uncontrolled systemic disease or active infection including hepatitis B, hepatitis C and known active human immunodeficiency virus (HIV) defined as \>200 copies of HIV per ml of blood, active bleeding diatheses or renal transplant. NOTE: testing for HIV, HBV, and HCV status prior to enrolment is not necessary unless clinically indicated.
• Participant with history of HBV infection will be eligible if on stable anti-viral therapy for \> 4 weeks prior to the planned first dose of study intervention and viral load confirmed as undetectable during Screening.
• Participant with history of HBC infection will be eligible the participant has received curative treatment and viral load was confirmed as undetectable during Screening.
• History of another primary malignancy except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and with the following exception. Patients with a history of another primary cancer treated with curative intent more than 3 years before study entry, who are not receiving any anti-cancer therapy, have a risk of disease recurrence lower than 10% as evaluated by the local Investigator, and who have no toxicity from previous treatment are eligible.
• Participants with active autoimmune disease requiring immunosuppressive treatment, including inflammatory bowel disease (ulcerative colitis or Crohn's disease), within 2 years of screening. NOTE: The following exceptions are permitted:
• Vitiligo
• Alopecia
• Managed hypothyroidism (on stable replacement doses)
• Asymptomatic adrenal insufficiency (on stable replacement doses)
• Psoriasis

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Northwell Health: collaborator
• Immunocore Ltd: collaborator

Study Sites (15)

Northwell Health -Center for Advanced Medicine

Lake Success, New York, 11042, United States

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

Centre Antoine Lacassagne

Nice, FR 06189, France

RECRUITING

Institut Curie - Hôpital de Paris

Paris, 75248, France

RECRUITING

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12200, Germany

RECRUITING

Universitaets Krankenhaus Eppendorf - Universitaetsklinikum Hamburg-Eppendorf KE - University Cancer Center

Hamburg, 20246, Germany

RECRUITING

Universitaetsklinikum Heidelberg - Frauenklinik / Hautklinik

Heidelberg, DE 69120, Germany

RECRUITING

Leiden University Medical Centre

Leiden, 2300, Netherlands

RECRUITING

Erasmus MC

Rotterdam, NL 3015 GD, Netherlands

RECRUITING

Maria Sklodowska-Curie Memorial Cancer Centre - Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw, 02 781, Poland

RECRUITING

Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

Hospital Clinico Universitario De Valladolid

Valladolid, 47003, Spain

RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, SE 413 45, Sweden

RECRUITING

The Clatterbridge cancer Center NHS foundation Trust - Clatterbridge Cancer Center - Liverpool

Liverpool, GB L7 8YA, United Kingdom

RECRUITING

East and North Hertfordshire NHS Trust - Mount Vernon Hospital

Northwood, HA6 2RN, United Kingdom

RECRUITING

MeSH Terms

Conditions

Uveal Melanoma

Interventions

tebentafusp

Condition Hierarchy (Ancestors)

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

Study Officials

• Paul Nathan

  Mount Vernon Cancer Centre, Northwood, UK

  PRINCIPAL INVESTIGATOR

• Richard D. Carvajal

  Northwell Health Cancer Institute, NY, USA

  PRINCIPAL INVESTIGATOR

• Serge Leyvraz

  Charité Hospital, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

EORTC HQ

CONTACT

+32 2 774 16 11; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 7, 2024
• Study Start: November 11, 2024
• Primary Completion (Estimated): November 1, 2032
• Study Completion (Estimated): November 1, 2032
• Last Updated: June 30, 2026

Record last verified: 2026-06

Locations

BE (1); SE (1); DE (3); ES (2); PL (1); GB (2); FR (2); NL (2); US (1)