TEBENTAFUSP for Metastatic uveal melanoma | Metastatic uveal melanoma (HLA-A*02:01 positive)

Inclusion criteria

• {"criterion_text":"- written informed consent"}
• {"criterion_text":"- Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 8.3, for the course of the study starting with the first dose of study therapy through at least 1 weeks after the last dose of treatment"}
• {"criterion_text":"- Will and ability to comply with the protocol"}
• {"criterion_text":"- Age ≥18 years"}
• {"criterion_text":"- Female and male"}
• {"criterion_text":"- PS (ECOG) 0 or 1"}
• {"criterion_text":"- Histologically or cytologically confirmed metastatic uveal melanoma HLA-A*02:01 positive"}
• {"criterion_text":"- Presence of liver metastases, at least one measurable lesion (RECIST v 1.1), with largest liver metastasis ≤ 8 cm"}
• {"criterion_text":"- Adequate bone marrow, renal and liver functions: absolute neutrophil count > 1.0 x 109/L; absolute lymphocyte count > 0.5 x 109/L; platelet count > 100 x 109/L;hemoglobin > 8 g/dl;serum creatinine < 1.5 x upper limit of normal (ULN) and/or creatinine clearance > 50 ml/min;total bilirubin < 1.5 x ULN (with the exception of patients with Gilbert Syndrome who will be excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN); alanine aminotransferase < 3.0 x ULN; aspartate aminotransferase < 3.0 x ULN"}
• {"criterion_text":"- Woman of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drugs"}
• {"criterion_text":"- Male subjects with female partners of childbearing potential must be willing to use adequate contraception as outlined in Section 8.3 – of the protocol, starting with the first dose of study therapy through at least 1 weeks after the last dose of treatment"}

Exclusion criteria

• {"criterion_text":"- Previous systemic therapy for metastatic uveal melanoma"}
• {"criterion_text":"- other serious or uncontrolled medical disorder, active infection, physical exam or laboratory findings, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a subject’s ability to comply with the study requirements"}
• {"criterion_text":"- Previous liver directed therapy"}
• {"criterion_text":"- Largest liver metastasis > 8 cm"}
• {"criterion_text":"- Symptomatic central nervous system metastases"}
• {"criterion_text":"- Participants with clinically significant cardiac disease or impaired cardiac function, including any of the following: - Congestive heart failure (New York Heart Association Class ≥ 3). - Uncontrolled hypertension (consistent findings of systolic blood pressure > 160 mmHg or diastolic > 110 mmHg). - History of ventricular arrhythmia currently requiring medical treatment. - Uncontrolled atrial fibrillation. - Electrocardiogram (ECG) QT interval corrected > 470 msec during screening obtained on triplicate ECGs or known history of congenital prolonged QT syndrome. - Acute myocardial infarction or unstable angina pectoris ≤ 6 months prior to screening"}
• {"criterion_text":"- Morning cortisol < lower limit of normal (unless the participant has asymptomatic adrenal insufficiency and is receiving stable replacement doses)"}
• {"criterion_text":"- Participants with active autoimmune disease requiring immunosuppressive treatment, including inflammatory bowel disease (ulcerative colitis or Crohn’s disease), within2 years of screening. 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"}
• {"criterion_text":"- Participants who received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of the planned first dose of study intervention. The following exceptions are permitted: - Treatment for well-controlled and asymptomatic adrenal insufficiency, but replacement dosing is limited to prednisone ≤ 12 mg daily or the equivalent. - Local steroid therapies (eg, optic, ophthalmic, intra-articular, or inhaled medications). - Premedication for allergy to contrast reagent. - Steroids for management of CNS metastases > 14 days prior to the planned first dose of study intervention. - To treat asthma or chronic obstructive pulmonary disease exacerbations > 14 days prior to the planned first dose of study intervention (only short-term oral or IV use in doses>12 mg/day prednisone equivalent). - For inhalation in the management of asthma or chronic obstructive pulmonary disease. - Any premedications required per protocol"}
• {"criterion_text":"- Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) or active malignancy requiring intervention"}
• {"criterion_text":"- Hypersensitivity to the active substance or to any of the excipients"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the progression-free survival, which will be calculated from the day of treatment initiation to the progression. The PFS rate at 6 months will be evaluated","definition_or_measurement_approach":"Progression-free survival (PFS) calculated from day of treatment initiation to progression; PFS rate at 6 months will be evaluated."}

Secondary endpoints

• {"endpoint_text":"- disease control rate at first tumor assessment","definition_or_measurement_approach":"Measured as disease control rate at the first tumor assessment (assessment per RECIST v1.1)."}
• {"endpoint_text":"- objective response rate","definition_or_measurement_approach":"Objective response rate assessed per tumor response criteria (e.g., RECIST v1.1)."}
• {"endpoint_text":"- overall survival","definition_or_measurement_approach":"Overall survival (OS) measured from treatment initiation to death from any cause."}
• {"endpoint_text":"- treatment duration","definition_or_measurement_approach":"Duration of time on study treatment (time from treatment start to discontinuation)."}
• {"endpoint_text":"- time to subsequent treatment initiation","definition_or_measurement_approach":"Time from study treatment initiation to start of next anti-cancer therapy."}
• {"endpoint_text":"- safety","definition_or_measurement_approach":"Safety assessed by adverse events and laboratory evaluations as per protocol."}
• {"endpoint_text":"- evaluation of patients’ circulating immune profile and inflammatory microenvironment of uveal melanoma and correlation with PFS","definition_or_measurement_approach":"Characterisation of circulating immune profile and inflammatory tumor microenvironment with correlation analyses versus PFS."}
• {"endpoint_text":"- analysis of ctDNA and correlation with PFS and OS","definition_or_measurement_approach":"Analysis of circulating tumor DNA (ctDNA) during treatment and correlation with PFS and OS."}

Italy

Earliest CTIS Part Ii Submission Date

16-06-2025

Latest Decision Or Authorization Date

21-07-2025

Processing Time Days

35

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Immunocore Limited","duties_or_roles":"Source of monetary support","organisation_type":""}