TEBENTAFUSP for Metastatic uveal melanoma

Inclusion criteria

• {"criterion_text":"- Patients must have histologically confirmed metastatic uveal melanoma with Human leukocyte antigen-A*0201 positive determined by local assay.\n- Patients with histologically proven metastatic uveal melanoma in the liver with resectable or potentially resectable liver metastases evaluated by imaging in a multidisciplinary committee. Metastasis can be considered resectable by any of the following: a. Minor resection (i.e., less than a hemihepatectomy) b. Major resection (i.e., hemihepatectomy or extended hepatectomy) c. Bilobar resection (including atypical resection).\n- Must meet the following criteria related to prior treatment: No prior sistemic therapy in the metastasic or advanced setting including chemotherapy, inmunotherapy, or targeted therapy; No prior local, liver-directed therapy inlcuding chemotherapy, radiotherapy, radiofrecuency ablation (RFA), or embolization; Prior neoadjuvant therapy is allowed provided it was administered in the curative setting in patients with localized disease\n- Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved written and signed informed consent.\n- Male or female patients age ≥ 18 years of age at the time of informed consent\n- Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-1 (Appendix 4)\n- Adequate organ function as defined below (without transfusion): a. Hemoglobin ≥ 9.0g/dL. b. Absolute neutrophil count (ANC) >1.5 x10⁹/L(>1500 per mm³). c. Platelet count ≥ 100 x10⁹/L (>75000 per mm³). d. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the Coordinating Investigator. e. Both AST and ALT must be <5 x ULN. f. Creatinine clearance ≥ 50 ml/min calculated be Cockcroft-Gault (Table 4) or another validated method. g. Potassium, magnessium, corrected calcium or phosphate abnormality of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) > grade 1."}

Exclusion criteria

• {"criterion_text":"- Presence of extrahepatic disease\n- 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 1 week after the final dose of investigational product. Highly effective methods of contraception are described in Appendix 5.\n- Male patients must be surgically sterile or use double barrier contraception methods from enrollment through tratment and for 1 week following administration of the last dose of study drug.\n- Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug.\n- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated.\n- Previous treatment with Tebentafusp\n- Patients receiving systemic steroid therapy or any other immunosuppressive medication at any dose level. Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable.\n- Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary).\n- Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF, M-CSF) ≤ 2 week prior to the star of study drug. Patients must have completed therapy with hematopoietic colony-stimulating factor at least 2 weeks before the first dose of study drug is given. An erythoid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the pacient is not red blood cel transfusion dependent.\n- Known history of human immunodeficiency virus (HIV) infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulations.\n- Patients with concomitant maligancy other than non-melanoma skin cancer, or superficial bladder cancer controlled with local treatment. Patients with prior malignancy must have been disease free for 5 years.\n- History of severe hypersensitibity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies.\n- Hypersensitivity to the active substance of tebentafusp or to any of its excipients, including: Citric acid monohydrate (E330) Di-sodium hydrogen phosphate (E339) Mannitol (E421) Trehalose Polysorbate 20 (E432).\n- Clinically significant cardiac disease or impaired cardiac function, including any of the following: a. Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association ≥ 2), uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment. b. QTcF > 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome. c. Acute myocardial infarction or unstable angina pectoris < 6 months prior to Screening.\n- History of adrenal insuffiency\n- History of intersticial lung disease\n- History of pneumonitis that required corticosteroid treatment or current pneumonitis\n- History of colitis or inflammatory bowel disease\n- Patients whose circumstances will not permit study completion or adequate follow up.\n- Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation)"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint for NEO-TB trial is the pathological complete response (pCR) rate, defined as no presence of residual disease assessed by biopsy or surgical resection at 7 months (+/- 1 month) after the start of the scheduled tratment with tebentafusp. Patients with CR according to RECIST after 6 months who do not enter surgery phase and continue treatment with tebentafusp will be considered as achieving pCR as well.","definition_or_measurement_approach":"Pathological complete response (pCR) rate defined as absence of residual disease assessed by biopsy or surgical resection at 7 months (+/- 1 month) after start of scheduled treatment; patients with CR per RECIST at 6 months who continue treatment without surgery are also considered pCR."}

Secondary endpoints

• {"endpoint_text":"- Secondary efficacy endpoints: ● Objecitve response rate (ORR) according to RECIST 1.1 ● Disease control rate (DCR) according to RECIST 1.1 ● Relapse-free survival (RFS) according to RECIST 1.1 ● Event-free survival (EFS) ● Overall survival (OS)","definition_or_measurement_approach":"Efficacy endpoints assessed according to RECIST 1.1 (ORR, DCR, RFS) and time-to-event measures (EFS, OS)."}
• {"endpoint_text":"- Secondary safety endpoints: ● Adverse events (AE) ● Treatment-related AEs (TRAEs)","definition_or_measurement_approach":"Safety endpoints captured as incidence and severity of adverse events and treatment-related adverse events (per NCI CTCAE or study-specified criteria)."}

Other endpoints

• {"endpoint_text":"- Exploratory endpoints:●Molecular biomarkers determined from liver biopsies at baseline and fresh samples from liver resections in lesions with viable tumors and samples of peripheral blood\n- Exploratory endpoints: ●Central assessment of TCR populations and peripheral lymphocytes memory cells in blood samples before/after tebentafusp and in the prospective fresh samples from liver resections\n- Exploratory endpoints: ●Correlation between ctDNA levels and presence of CTCs in blood samples at several time points and clinical efficacy and safety outcomes","definition_or_measurement_approach":"Exploratory biomarker analyses from liver biopsies, fresh resection samples and peripheral blood; central TCR and peripheral lymphocyte memory cell assessments; correlation analyses of ctDNA/CTCs with clinical outcomes."}

Germany

Earliest CTIS Part Ii Submission Date

16-06-2025

Latest Decision Or Authorization Date

25-02-2026

Processing Time Days

254

Number Of Sites

1

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

31-03-2025

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

350

Number Of Sites

3

Number Of Participants

13

Primary sponsor

Full Name

Grupo Espanol Multidisciplinar De Melanoma

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain