Clinical trial • Phase III • Oncology|Ophthalmology

TEBENTAFUSP for Uveal melanoma

Phase III trial of TEBENTAFUSP for Uveal melanoma.

Overview

Trial Therapeutic Area
Oncology|Ophthalmology
Trial Disease
Uveal melanoma
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
29-05-2024
First CTIS Authorization Date
18-09-2024

Trial design

Randomised, open-label, adjuvant tebentafusp (kimmtrak 100 micrograms/0.5 ml concentrate for solution for infusion; active substance tebentafusp) versus observation (no active treatment). dosing schedule not specified in ctis record.-controlled Phase III trial in France, Germany, Ireland and others.

Randomised
Yes
Open Label
Yes
Comparator
Adjuvant tebentafusp (KIMMTRAK 100 micrograms/0.5 mL concentrate for solution for infusion; active substance tebentafusp) versus observation (no active treatment). Dosing schedule not specified in CTIS record.
Target Sample Size
110

Eligibility

Recruits 110 Vulnerable population flag is set (isVulnerablePopulationSelected: true). Consent requirements: written pre-screening informed consent and written informed consent according to ICH/GCP and local regulations are required. Only adults (18 years or older) are eligible, so consent is provided by the participant; no assent/parental consent procedures for minors are described. Participant information and consent documents are provided (languages and versions available in the repository)..

Pregnancy Exclusion
Screening: Evidence of post-menopausal status or negative urinary or serum pregnancy test for women of childbearing potential (WOCBP) within 3 days prior to randomization.
Vulnerable Population
Vulnerable population flag is set (isVulnerablePopulationSelected: true). Consent requirements: written pre-screening informed consent and written informed consent according to ICH/GCP and local regulations are required. Only adults (18 years or older) are eligible, so consent is provided by the participant; no assent/parental consent procedures for minors are described. Participant information and consent documents are provided (languages and versions available in the repository).

Inclusion criteria

  • {"criterion_text":"- Pre-screening: Primary non-metastatic UM, except iris melanoma, after definitive treatment either by surgery or radiotherapy\n- Screening: Time-interval between the end of primary treatment and the randomization less than or equal to 12 weeks\n- Screening: Evidence of post-menopausal status or negative urinary or serum pregnancy test for women of childbearing potential (WOCBP) within 3 days prior to randomization.\n- Screening: 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.\n- Screening: 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.\n- Screening: Written informed consent according to ICH/GCP and local regulations\n- Pre-screening: Time from primary treatment smaller than 11 weeks (note that the maximum time between primary treatment and randomization is 12 weeks)\n- Pre-screening: 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\n- Pre-screening: ECOG performance status of 0 or 1\n- Pre-screening: 18 years or older\n- Pre-screening: Written pre-screening informed consent according to ICH/GCP and local regulations\n- Screening: HLA-A*02:01 positivity by local assessment\n- Screening: No evidence of UM recurrence, as evidenced by the required baseline imaging performed within 4 weeks prior to randomization\n- Screening: Adequate organ function:• Serum creatinine ≤ 1.5 × ULN and/or creatinine clearance (calculated using Cockcroft-Gault formula, or measured) ≥ 40 mL/minute • Total bilirubin ≤ 1.5 × ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin ≥1.5 × ULN • Alanine aminotransferase ≤ 3 × ULN • Aspartate aminotransferase ≤ 3 × ULN • Absolute neutrophil count ≥ 1.0 × 10^9/L • Absolute lymphocyte count ≥ 0.5 × 10^9/L • Platelet count ≥ 150 × 10^9/L • Haemoglobin ≥ 10 g/dL"}

Exclusion criteria

  • {"criterion_text":"- 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\n- Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to randomization\n- 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. • 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.\n- 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\n- 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 • Resolved childhood asthma/atopy • Well-controlled asthma • Type I diabetes mellitus\n- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial\n- Known contraindication to imaging tracer or any product of contrast media and MRI and/or CT contraindications."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- RFS, defined as time between randomization and local recurrence, distant recurrence, or death, whichever occurs first.","definition_or_measurement_approach":"Time between randomization and local recurrence, distant recurrence, or death, whichever occurs first."}

Secondary endpoints

  • {"endpoint_text":"- OS, defined as time between randomization and death","definition_or_measurement_approach":"Time between randomization and death."}
  • {"endpoint_text":"- Safety of tebentafusp.","definition_or_measurement_approach":""}

Other endpoints

  • {"endpoint_text":"- Biobanking, quality of life, Biomarker driven trial","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
110
Recruitment Window Months
97
Consent Approach
Written informed consent is required according to ICH/GCP and local regulations; a written pre-screening informed consent is also specified. Consent is provided by adult participants (≥18 years). Subject information and informed consent forms (pre‑screening and enrolment) are available in multiple languages (English, French, Spanish, Italian, Dutch, Polish, German, Swedish and local language versions where provided).

Geography

Total Number Of Sites
18
Total Number Of Participants
200

France

Earliest CTIS Part Ii Submission Date
27-08-2024
Latest Decision Or Authorization Date
15-12-2025
Processing Time Days
475
Number Of Sites
2
Number Of Participants
24

Sites

Site Name
Centre Antoine Lacassagne
Department Name
Oncology
Principal Investigator Name
Agnes Ducoulombier
Principal Investigator Email
Agnes.DUCOULOMBIER@nice.unicancer.fr
Contact Person Name
Agnes Ducoulombier
Site Name
Institut Curie
Department Name
Oncology
Principal Investigator Name
Manuel Rodrigues
Principal Investigator Email
manuel.rodrigues@curie.fr
Contact Person Name
Manuel Rodrigues
Contact Person Email
manuel.rodrigues@curie.fr

Germany

Earliest CTIS Part Ii Submission Date
09-09-2024
Latest Decision Or Authorization Date
12-05-2026
Processing Time Days
610
Number Of Sites
4
Number Of Participants
48

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik fuer Haematologie, Onkologie und Tumorimmunologie
Principal Investigator Name
Caroline Anna Peuker
Principal Investigator Email
Caroline-Anna.Peuker@charite.de
Contact Person Name
Caroline Anna Peuker
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Dermatology
Principal Investigator Name
Christoffer Gebhardt
Principal Investigator Email
ch.gebhardt@uke.de
Contact Person Name
Christoffer Gebhardt
Contact Person Email
ch.gebhardt@uke.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Hautklinik
Principal Investigator Name
Jessica Hassel
Principal Investigator Email
jessica.hassel@med.uni-heidelberg.de
Contact Person Name
Jessica Hassel
Site Name
Universitaetsklinikum Essen AöR
Department Name
Medical Oncology
Principal Investigator Name
Halime Kalkavan
Principal Investigator Email
Halime.kalkavan@uk-essen.de
Contact Person Name
Halime Kalkavan
Contact Person Email
Halime.kalkavan@uk-essen.de

Ireland

Earliest CTIS Part Ii Submission Date
25-08-2025
Latest Decision Or Authorization Date
11-05-2026
Processing Time Days
259
Number Of Sites
1
Number Of Participants
6

Sites

Site Name
St Vincent's University Hospital
Department Name
Oncology
Principal Investigator Name
Sarah Lochrin
Principal Investigator Email
sarahlochrin@svhg.ie
Contact Person Name
Sarah Lochrin
Contact Person Email
sarahlochrin@svhg.ie

Netherlands

Earliest CTIS Part Ii Submission Date
11-09-2024
Latest Decision Or Authorization Date
12-05-2026
Processing Time Days
608
Number Of Sites
2
Number Of Participants
24

Sites

Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Oncology and Radiology & Nuclear Medicine
Principal Investigator Name
Astrid van der Veldt
Principal Investigator Email
a.vanderveldt@erasmusmc.nl
Contact Person Name
Astrid van der Veldt
Contact Person Email
a.vanderveldt@erasmusmc.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Medical
Principal Investigator Name
Ellen Kapiteijn
Principal Investigator Email
h.w.kapiteijn@lumc.nl
Contact Person Name
Ellen Kapiteijn
Contact Person Email
h.w.kapiteijn@lumc.nl

Poland

Earliest CTIS Part Ii Submission Date
23-08-2024
Latest Decision Or Authorization Date
15-05-2026
Processing Time Days
630
Number Of Sites
1
Number Of Participants
15

Sites

Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Oncology
Principal Investigator Name
Piotr Rutkowski
Principal Investigator Email
piotr.rutkowski@nio.gov.pl
Contact Person Name
Piotr Rutkowski
Contact Person Email
piotr.rutkowski@nio.gov.pl

Spain

Earliest CTIS Part Ii Submission Date
13-06-2024
Latest Decision Or Authorization Date
12-05-2026
Processing Time Days
698
Number Of Sites
3
Number Of Participants
24

Sites

Site Name
Institut Catala D'oncologia
Department Name
Oncology
Principal Investigator Name
Josep Piulats Rodriguez
Principal Investigator Email
jmpiulats@iconcologia.net
Contact Person Name
Josep Piulats Rodriguez
Contact Person Email
jmpiulats@iconcologia.net
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Principal Investigator Name
Guillermo Antonio de Velasco Oria de Rueda
Principal Investigator Email
gdvelasco.gdv@gmail.com
Contact Person Name
Guillermo Antonio de Velasco Oria de Rueda
Contact Person Email
gdvelasco.gdv@gmail.com
Site Name
Hospital Clinico Universitario De Valladolid
Department Name
Oncology
Principal Investigator Name
Rafael Lopez Castro
Principal Investigator Email
rafalopezcastro@gmail.com
Contact Person Name
Rafael Lopez Castro
Contact Person Email
rafalopezcastro@gmail.com

Sweden

Earliest CTIS Part Ii Submission Date
08-08-2025
Latest Decision Or Authorization Date
12-05-2026
Processing Time Days
277
Number Of Sites
1
Number Of Participants
14

Sites

Site Name
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Department Name
Medical Oncology
Principal Investigator Name
Lars Ny
Principal Investigator Email
Lars.ny@oncology.gu.se
Contact Person Name
Lars Ny
Contact Person Email
Lars.ny@oncology.gu.se

Italy

Earliest CTIS Part Ii Submission Date
27-08-2024
Latest Decision Or Authorization Date
15-05-2026
Processing Time Days
626
Number Of Sites
3
Number Of Participants
24

Sites

Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Melanoma, Cancer Immunotherapy and Development Therapeutics
Principal Investigator Name
Paolo Ascierto
Principal Investigator Email
p.ascierto@istitutotumori.na.it
Contact Person Name
Paolo Ascierto
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Medical Oncology
Principal Investigator Name
Michele Del Vecchio
Principal Investigator Email
michele.delvecchio@istitutotumori.mi.it
Contact Person Name
Michele Del Vecchio
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Oncology
Principal Investigator Name
Ernesto Rossi
Principal Investigator Email
ernesto.rossi@policlinicogemelli.it
Contact Person Name
Ernesto Rossi

Belgium

Earliest CTIS Part Ii Submission Date
28-08-2024
Latest Decision Or Authorization Date
11-05-2026
Processing Time Days
621
Number Of Sites
1
Number Of Participants
21

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
Oncology
Principal Investigator Name
Jean-Francois Baurain
Principal Investigator Email
jean-francois.baurain@uclouvain.be
Contact Person Name
Jean-Francois Baurain

Sponsor

Primary sponsor

Full Name
European Organisation For Research And Treatment Of Cancer
Organisation Type
Patient organisation/association
Country Of Registered Address
Belgium

Third parties

  • {"country":"France","full_name":"Institut Curie","duties_or_roles":"External Imaging Reviewer","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Azienda Ospedaliera Universitaria Integrata Verona","duties_or_roles":"External Imaging Reviewer","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"France","full_name":"Cryoport France","duties_or_roles":"Sample Storage","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Stichting EuroQol Research Foundation","duties_or_roles":"Provider Quality of Life questionnaires","organisation_type":"Patient organisation/association"}
  • {"country":"United States","full_name":"Radionix LLC","duties_or_roles":"External Imaging Reviewer","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
KIMMTRAK 100 micrograms/0.5 mL concentrate for solution for infusion
Active Substance
TEBENTAFUSP
Modality
Peptide/protein/enzyme
Routes Of Administration
INFUSION
Route
INFUSION
Authorisation Status
Marketing authorisation EU/1/22/1630/001
Orphan Designation
Yes
Maximum Dose
68 µg (maxDailyDoseAmount)

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