Neoadjuvant Tebentafusp in Patients With Metastatic Uveal Melanoma

NCT07057596 | Recruiting Phase 2 DMC

• 2 other identifiers: GEM 23022023-509076-42-00
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 4

Brief Summary

Uveal melanoma (UM) is a rare type of melanoma, with an incidence of 4.4 cases per million in Europe each year. During recent years, different treatment approaches have been tested in patients with metastatic UM. Responses have been reported primarily with localized treatment in patients with a limited number of liver metastases. In cases of diffuse liver involvement or extrahepatic disease, systemic therapies are justified. However, to date, systemic therapies such as targeted therapy with selumetinib or conventional chemotherapy have failed in metastatic UM. Neo-TB is a Phase II, single arm, multicentre clinical trial designed to evaluate efficacy and safety of tebentafusp used as a single agent in patients with metastatic uveal melanoma with resectable / potentially resectable liver metastasis and absence of extrahepatic disease. The main questions it aims to answer are:

1. 1.Which is the capacity of tebentafusp used as a single agent to generate pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable liver metastasis and absence of extrahepatic disease.
2. 2.Which is the efficacy of tebentafusp used as a single agent to maintain disease control and delay relapse / progression.
3. 3.Which is the safety of tebentafusp used as a single agent in metastatic uveal melanoma.

Conditions

Mestastatic Uveal Melanoma

Keywords

Melanoma; Tebentafusp; Metastatic; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  Pathological complete response (pCR) rate, the primary efficacy endpoint: Defined as the rate of patients with metastatic uveal melanoma with resectable / potentially resectable liver metastasis and free of extrahepatic disease, who have no presence of residual disease assessed by biopsy or surgical resection at 7 months (+/- 1 month) after the start of the scheduled treatment with tebentafusp. pCR will be assessed locally on tumor samples from gross resection or biopsies obtained at 7 months (+/- 1 month) after the start of tebentafusp.

  Throughout the study period, at 7 months (+/- 1 month) from the start of treatment]

Secondary Outcomes (6)

• Objective response rate (ORR) of neoadjuvant tebentafusp

  Throughout the study period, at 6 months from the start of treatment

• Disease control rate (DCR) of neoadjuvant tebentafusp

  Throughout the study period, at 6 months from the start of treatment

• Relapse-free survival (RFS) at end of follow-up.

  Throughout the study period, approximate average of 24 months since the start of treatment

• Relapse-free survival (RFS) at at 6-months

  Throughout the study period, at 6 months from the start of treatment

• Relapse-free survival (RFS) at 12 months

  Throughout the study period, at 12 months from the start of treatment

Study Arms (1)

Neoadjuvant Tebentafusp

EXPERIMENTAL

Patients will receive tebentafusp intravenously (IV) weekly for 6 months with liver directed imaging every 2 months to identify rapid progressors. Rapid progressors will discontinue tebentafusp and have surgical resection if considered feasible. After 6 months, patients with complete response (CR) according to RECIST will continue tebentafusp therapy. Surgery might be an option if deem appropriate by local PI); while patients achieving partial response or stable disease will be evaluated for tumor resection and will enter into Surgery phase. Surgery will be conducted 7 months (+/- 1 month). If progressioh disease (PD) occurs earlier surgery can happen earlier. After surgery, patients without pCR or R0 surgery will maintain tebentafusp until disease relapse, unacceptable toxicity or patient withdrawal. Patients with pCR and R0 will continue tebentafusp therapy for 1 additional year or until disease relapse, unacceptable toxicity or patient withdrawal.

Drug: Tebentafusp

Interventions

Tebentafusp DRUG

Patients will receive tebentafusp intravenously (IV) weekly for 6 months with liver directed imaging every 2 months to identify rapid progressors. Tebentafusp will be administered at 20 micrograms on W1D1, 30 micrograms on W2D1, and 68 micrograms once every week thereafter. After 6 months, patients with complete response (CR) according to RECIST will continue tebentafusp therapy (surgery might be an option if deem appropriate by local PI); while patients achieving partial response or stable disease will be evaluated for tumor resection and will enter into Surgery phase. Surgery will be conducted 7 months (+/- 1 month). If progressioh disease (PD) occurs earlier surgery can happen earlier. After surgery, patients without pCR or R0 surgery will maintain tebentafusp until disease relapse, unacceptable toxicity or patient withdrawal. Patients with pCR and R0 will continue tebentafusp therapy for 1 additional year or until disease relapse, unacceptable toxicity or patient withdrawal.

Neoadjuvant Tebentafusp

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed metastatic uveal melanoma with Human leukocyte antigen-A\*0201 positive determined by local assay.
• Patients with histologically proven metastatic uveal melanoma in the liver with reectable or potentially resectable liver metastases evaluated by imaging in a multidisciplinary committee. Metastasis can be considered resectable by any of the following:
• Minor resection (i.e., less than a hemihepatectomy)
• Major resection (i.e., hemihepatectomy or extended hepatectomy)
• Bilobar resection (including atypical resection).
• Must meet the following criteria related to prior treatment:
• No prior systemic therapy in the metastatic or advanced setting including chemotherapy, immunotherapy, or targeted therapy.
• No prior local, liver-directed therapy including chemotherapy, radiotherapy, radiofrequency ablation (RFA), or embolization.
• Prior neoadjuvant or adjuvant therapy is allowed provided it was administered in the curative setting in patients with localized disease.
• Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written and signed informed consent.
• Male or female patients age ≥ 18 years of age at the time of informed consent.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-1
• Adequate organ function as defined below (without transfusion):
• Hemoglobin ≥9.0 g/dL.
• Absolute neutrophil count (ANC) \>1.5 x 109/L (\> 1500 per mm3).

You may not qualify if:

• Presence of extrahepatic disease.
• Patients with concomitant malignancy 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.
• History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies.
• 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.
• Acute myocardial infarction or unstable angina pectoris \< 6 months prior to Screening.
• History of adrenal insufficiency.
• History of interstitial lung disease
• History of pneumonitis that required corticosteroid treatment or current pneumonitis
• History of colitis or inflammatory bowel disease.
• 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.
• Known history of human immunodeficiency virus (HIV) infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulations.
• 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.
• Previous treatment with Tebentafusp.

Sponsors & Collaborators

• Grupo Español Multidisciplinar de Melanoma: lead

Study Sites (4)

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 10117, Germany

RECRUITING

Institut Catala d'Oncologia (ICO) Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

NOT YET RECRUITING

Hospital La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Consorcio Hospital General Universitario de Valencia

Valencia, Valencia, 46014, Spain

RECRUITING

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

tebentafusp

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Josep Maria Piulats, M.D., Ph.D.

  Institut Catala d'Oncologia (ICO) Hospitalet

  STUDY CHAIR

Central Study Contacts

Federico Nepote

CONTACT

934344412; investigacion@mfar.net

Josep Maria Piulats, M.D., Ph.D.

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: NEO-TB is a non-randomized, single arm, multi-centre, phase II study of Tebentafusp monotherapy in subjects with resectable / potentially resectable disease within the liver and absence of extra-liver disease. The trial will enroll 19 patient male and female, ≥ 18 years, with ECOG PS 0-1 patients with metastatic uveal melanoma (HLA)-A\*02:01 positive who have resectable or potentially resectable metastatic lesions only in the liver. The study is divided into 4 phases: Screening, Treatment, Surgery and Follow-up. All patients will undergo periodic tumor assessments by Computed Tomography (TC) o Magnetic Resonance Imaging (MRI) scan every 8 weeks ± 7 days from the start of study treatment and during the first 48 weeks of study. Tumor assessments will be performed every 12 weeks ± 7 days thereafter until relapse or patient withdrawal. After surgery, CT or MRI scans will be performed every 12 weeks ± 7 days thereafter, regardless of time after study inclusion.

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 10, 2025
• Study Start: July 18, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); ES (3)