Mestastatic Uveal MelanomaPhase 2NEO-TBNCT07057596
Neoadjuvant Tebentafusp in Patients With Metastatic Uveal Melanoma
A Phase 2 study testing Tebentafusp in people with Mestastatic Uveal Melanoma, run by Grupo Español Multidisciplinar de Melanoma at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mestastatic Uveal Melanoma
- What is being tested?
- Tebentafusp
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 18 Jul 2025to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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).
- Platelet count ≥ 100 x 109/L (>75,000 per mm3).
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the Coordinating Investigator.
- Both AST and ALT must be < 5 x ULN.
- Creatinine clearance ⩾50 ml/min calculated by Cockcroft-Gault (Table 4) or another validated method.
- Potassium, magnesium, corrected calcium or phosphate abnormality of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) > grade 1.
Who cannot join
- 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.
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- 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.
- 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.
- 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).
- Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF, M-CSF) ≤ 2 weeks prior to the start 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 erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is not red blood cell transfusion dependent.
- 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).
- Patients whose circumstances will not permit study completion or adequate follow up.
- 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).
- 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.
- Male patients must be surgically sterile or use double barrier contraception methods from enrollment through treatment and for 1 week following administration of the last dose of study drug.
Trial locations and contacts
4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Josep Maria Piulats, M.D., Ph.D. contact
4 sites in 2 countries
Spain3 sites, 3 recruiting
- Recruiting
Institut Catala d'Oncologia (ICO) Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08908
Principal Investigator Selected by Sponsor,, M.D., Ph.D., +34 93 434 44 12, investigacion@mfar.net
- Recruiting
Hospital La Paz
Madrid, Madrid, 28046
A responsible person Selected by Sponsor,, M.D., Ph.D., +34 93 434 44 12, investigacion@mfar.net
- Recruiting
Consorcio Hospital General Universitario de Valencia
Valencia, Valencia, 46014
A responsible person Selected by Sponsor,, M.D., Ph.D., +34 93 434 44 12, investigacion@mfar.net
Germany1 site, 1 recruiting
- Recruiting
Charité - Universitätsmedizin Berlin
Berlin, State of Berlin, 10117
A responsible person Selected by Sponsor,, M.D., Ph.D., +34 93 434 44 12, investigacion@mfar.net
About this study
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.
Read more
The main questions it aims to answer are:
- 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.
- Which is the efficacy of tebentafusp used as a single agent to maintain disease control and delay relapse / progression.
- Which is the safety of tebentafusp used as a single agent in metastatic uveal melanoma.
The main hypothesis is that neoadjuvant treatment with Tebentafusp could achieve ≥20% pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable/potentially resectable liver metastasis and absence of extrahepatic disease. It is assumed that untreated patients would not present a pCR (response rate of ≤1%).
Read the detailed description
- RACIONAL Tebentafusp has demonstrated efficacy and safety and is indicated as monotherapy for the treatment of adult patients with human leukocyte antigen (HLA)-A*02:01-positive unresectable or metastatic uveal melanoma. The main hypothesis is that neoadjuvant treatment with Tebentafusp could achieve ≥20% pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable or potentially resectable liver metastasis and absence of extrahepatic disease.
- OBJECTIVES Primary Objective: to evaluate the ability of tebentafusp used as a single agent to generate pathological complete responses (pCR) in patients with metastatic uveal melanoma with resectable / potentially resectable liver metastases and absence of extrahepatic disease. Secondary objectives: to assess efficacy and safety of tebentafusp used as a single agent to maintain disease control and delay relapse / progression. Exploratory objectives:
- Study mechanisms of resistance to tebentafusp.
- Study correlation between pathological response and circulating tumor DNA (ctDNA) dynamics or circulating tumor cells (CTCs).
- Evaluate dynamics in T-cell receptor (TCR) populations and peripheral lymphocytes memory cells in blood samples before/after Tebentafusp and in the prospective fresh samples from liver resections.
- Primary Endpoint 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 treatment with tebentafusp.
- Secondary Endpoints
- Objective 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)
- Adverse events (AE)
- Treatment-related AEs (TRAEs)
- Molecular biomarkers determined from liver biopsies at baseline and fresh samples from liver resections in lesions with viable tumors and samples of peripheral blood.
- Study Design 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 Neo-TB study is divided into 4 phases: Screening, Treatment, Surgery and Follow-up. After informed consent is obtained, subjects will enter the Treatment phase. All patients will undergo periodic tumor assessments by CT or 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. Further CT/MRI scans could be performed upon suspicion of disease relapse according to standard clinical practice and physician criteria. The study includes the collection of tumor and blood samples for the determination of exploratory endpoints
- Study Population The trial will enroll 19 patients; 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. Patients with extrahepatic disease are not eligible. Patients will have not received previously other anti-tumor treatments.
- Study Treatment 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 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
- Ethical Considerations Patients with metastatic uveal melanoma have limited therapeutic options. Clinical guidelines recommend considering clinical trials.
Tebentafusp is approved for use as monotherapy in patients with uveal melanoma whose tumors are positive for (HLA)-A*02:01. In the phase 3 clinical trial, tebentafusp showed a significant improvement in overall survival compared to other standard therapies and therefore it is considered the treatment of choice for patients with (HLA)-A*02:01 positive tumors.
NEO-TB aims to use tebentafusp in the pathology for which it is indicated, with the only modification of combining its administration with surgical resection in patients already or potentially candidates for surgery, aiming to evaluate the pathological response. The guidelines also allow this multimodal treatment strategy with tebentafusp and surgery, so the trial could in some way consider the proposed intervention as low impact. Patients will be closely monitored, following an adaptive strategy to allow surgery if necessary, avoiding delays that limit tumor resection. Tebentafusp is the standard therapy for these patients, so its administration in the context of this trial is not expected to increase the risks already described associated with this treatment. Given the mechanism of action of tebentafusp, an increase in its toxicity due to the combination with surgery is not expected. Immunotherapies in combination with surgery are used in the perioperative setting as neoadjuvant and adjuvant strategies in patients with cutaneous melanoma and are safe. However, there is no published data with patients treated with tebentafusp in this context.
Given the limited therapeutic options and the current evidence and rationale for the use of tebentafusp and surgery, the risk-benefit ratio of this trial is considered positive. The potential benefit outweighs the risks
- Conditions
- Mestastatic Uveal Melanoma
- Being tested
- Tebentafusp
- Keywords
- Melanoma, Tebentafusp, Metastatic, Neoadjuvant
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TebentafuspDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tebentafusp |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Throughout the study period, at 7 months (+/- 1 month) from the start of treatment]
Secondary outcomes (6)
Objective response rate (ORR) of neoadjuvant tebentafusp
Assessed by the investigator through imaging follow-up (CT scan/MRI) using RECIST 1.1 up to surgical intervention. This will be considered as the percentage/proportion of patients with complete response (CR) or partial response (PR) as their overall best response throughout the study period. Objective responses will be assessed locally by the investigator according to RECIST, version 1.1, and indicating the change in size of tumors as compared with baseline, before the first dose of study treatment.
Measured: Throughout the study period, at 6 months from the start of treatment
Disease control rate (DCR) of neoadjuvant tebentafusp
Percentage/proportion of patients with complete response (CR) or partial response (PR), according to ORR definition for the trial, or maintained stable disease (SD) as their overall best response, assessed by imaging follow-up (CT scan/MRI) and RECIST 1.1 criteria. Stable disease should be maintained for at least 4 months to be considered as a DCR event. DCR will be assessed locally up to surgical intervention.
Measured: Throughout the study period, at 6 months from the start of treatment
Relapse-free survival (RFS) at end of follow-up.
Defined as the time from first study dosing date to the date of relapse after surgery according to RECIST 1.1 (Appendix 3) or death due to any cause. Patients who do not have surgical resection will be not evaluable for RFS endpoint. The RFS will be estimated by the Kaplan-Meier method. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment. RFS will be displayed graphically where appropriate.
RFS will be calculated as median / mean (95% CI) and for different timepoints:
- Proportion of patients without relapse at the end of follow-up.
- Proportion of patients relapse-free at 6-months, 12-months and as deemed opportune by the time of the analysis
The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable.
Measured: Throughout the study period, approximate average of 24 months since the start of treatment
Relapse-free survival (RFS) at at 6-months
Defined as the time from first study dosing date to the date of relapse after surgery according to RECIST 1.1 (Appendix 3) or death due to any cause. Patients who do not have surgical resection will be not evaluable for RFS endpoint. The RFS will be estimated by the Kaplan-Meier method. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment. RFS will be displayed graphically where appropriate.
RFS will be calculated as median / mean (95% CI) and for different timepoints:
- Proportion of patients without relapse at the end of follow-up.
- Proportion of patients relapse-free at 6-months, 12-months and as deemed opportune by the time of the analysis
The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable.
Measured: Throughout the study period, at 6 months from the start of treatment
Relapse-free survival (RFS) at 12 months
Defined as the time from first study dosing date to the date of relapse after surgery according to RECIST 1.1 (Appendix 3) or death due to any cause. Patients who do not have surgical resection will be not evaluable for RFS endpoint. The RFS will be estimated by the Kaplan-Meier method. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment. RFS will be displayed graphically where appropriate.
RFS will be calculated as median / mean (95% CI) and for different timepoints:
Proportion of patients relapse-free at 6-months, 12-months and as deemed opportune by the time of the analysis
The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable.
Measured: Throughout the study period, at 12 months from the start of treatment
Overall survival (OS)
Defined as the time elapsed from the first dose of study treatment until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact. OS will be summarized using the Kaplan-Meier method and displayed graphically where appropriate. The Cox proportional hazards model will be fitted to compute the hazard ratios on potential stratified groups if applicable. OS will be calculated as median / mean (95% CI) and OS rate for different timepoints deemed appropriate at the time of the analysis (i.e.1-year OS rate) will also be calculated.
Measured: Throughout the study period, at 12 months from the start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2025
- Study start18 Jul 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mestastatic Uveal MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Grupo Español Multidisciplinar de Melanoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Josep Maria Piulats, M.D., Ph.D., Study chair, Institut Catala d'Oncologia (ICO) Hospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07057596
- Sponsor's protocol ID
- GEM 2302
- Other IDs
- 2023-509076-42-00, 2023
- Acronym
- NEO-TB
- Status last verified
- Sep 2026
- First submitted
- 30 Jun 2025
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Tebentafusp in Patients With Metastatic Uveal Melanoma
- ClinicalTrials.gov ID
- NCT07057596
- Acronym / sponsor ID
- NEO-TB / GEM 2302
- Conditions
- Mestastatic Uveal Melanoma
- Keywords
- Melanoma, Tebentafusp, Metastatic, Neoadjuvant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Grupo Español Multidisciplinar de MelanomaUniversity, hospital or other
- Study start
- 18 Jul 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Which is the efficacy of tebentafusp used as a single agent to maintain disease control and delay relapse / progression.
- Which is the safety of tebentafusp used as a single agent in metastatic uveal melanoma.
The main hypothesis is that neoadjuvant treatment with Tebentafusp could achieve ≥20% pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable/potentially resectable liver metastasis and absence of extrahepatic disease. It is assumed that untreated patients would not present a pCR (response rate of ≤1%).
Detailed description
- RACIONAL Tebentafusp has demonstrated efficacy and safety and is indicated as monotherapy for the treatment of adult patients with human leukocyte antigen (HLA)-A*02:01-positive unresectable or metastatic uveal melanoma. The main hypothesis is that neoadjuvant treatment with Tebentafusp could achieve ≥20% pathological complete response (pCR) in patients with metastatic uveal melanoma with resectable or potentially resectable liver metastasis and absence of extrahepatic disease.
- OBJECTIVES Primary Objective: to evaluate the ability of tebentafusp used as a single agent to generate pathological complete responses (pCR) in patients with metastatic uveal melanoma with resectable / potentially resectable liver metastases and absence of extrahepatic disease. Secondary objectives: to assess efficacy and safety of tebentafusp used as a single agent to maintain disease control and delay relapse / progression. Exploratory objectives:
- Study mechanisms of resistance to tebentafusp.
- Study correlation between pathological response and circulating tumor DNA (ctDNA) dynamics or circulating tumor cells (CTCs).
- Evaluate dynamics in T-cell receptor (TCR) populations and peripheral lymphocytes memory cells in blood samples before/after Tebentafusp and in the prospective fresh samples from liver resections.
- Primary Endpoint 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 treatment with tebentafusp.
- Secondary Endpoints
- Objective 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)
- Adverse events (AE)
- Treatment-related AEs (TRAEs)
- Molecular biomarkers determined from liver biopsies at baseline and fresh samples from liver resections in lesions with viable tumors and samples of peripheral blood.
- Study Design 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 Neo-TB study is divided into 4 phases: Screening, Treatment, Surgery and Follow-up. After informed consent is obtained, subjects will enter the Treatment phase. All patients will undergo periodic tumor assessments by CT or 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. Further CT/MRI scans could be performed upon suspicion of disease relapse according to standard clinical practice and physician criteria. The study includes the collection of tumor and blood samples for the determination of exploratory endpoints
- Study Population The trial will enroll 19 patients; 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. Patients with extrahepatic disease are not eligible. Patients will have not received previously other anti-tumor treatments.
- Study Treatment 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 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
- Ethical Considerations Patients with metastatic uveal melanoma have limited therapeutic options. Clinical guidelines recommend considering clinical trials.
Tebentafusp is approved for use as monotherapy in patients with uveal melanoma whose tumors are positive for (HLA)-A*02:01. In the phase 3 clinical trial, tebentafusp showed a significant improvement in overall survival compared to other standard therapies and therefore it is considered the treatment of choice for patients with (HLA)-A*02:01 positive tumors.
NEO-TB aims to use tebentafusp in the pathology for which it is indicated, with the only modification of combining its administration with surgical resection in patients already or potentially candidates for surgery, aiming to evaluate the pathological response. The guidelines also allow this multimodal treatment strategy with tebentafusp and surgery, so the trial could in some way consider the proposed intervention as low impact. Patients will be closely monitored, following an adaptive strategy to allow surgery if necessary, avoiding delays that limit tumor resection. Tebentafusp is the standard therapy for these patients, so its administration in the context of this trial is not expected to increase the risks already described associated with this treatment. Given the mechanism of action of tebentafusp, an increase in its toxicity due to the combination with surgery is not expected. Immunotherapies in combination with surgery are used in the perioperative setting as neoadjuvant and adjuvant strategies in patients with cutaneous melanoma and are safe. However, there is no published data with patients treated with tebentafusp in this context.
Given the limited therapeutic options and the current evidence and rationale for the use of tebentafusp and surgery, the risk-benefit ratio of this trial is considered positive. The potential benefit outweighs the risks
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Tebentafusp | Experimental | Drug: TebentafuspPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
- Must meet the following criteria related to prior treatment:
- 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.
Key exclusion criteria (23 listed)
- 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:
- History of adrenal insufficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TebentafuspPatients 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. | Drug | Neoadjuvant Tebentafusp |
Primary outcome
Pathological complete response (pCR) rate
Time frame: Throughout the study period, at 7 months (+/- 1 month) from the start of treatment]
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.
6 secondary outcomes
Objective response rate (ORR) of neoadjuvant tebentafusp
Time frame: Throughout the study period, at 6 months from the start of treatment
Disease control rate (DCR) of neoadjuvant tebentafusp
Time frame: Throughout the study period, at 6 months from the start of treatment
Relapse-free survival (RFS) at end of follow-up.
Time frame: Throughout the study period, approximate average of 24 months since the start of treatment
Relapse-free survival (RFS) at at 6-months
Time frame: Throughout the study period, at 6 months from the start of treatment
Relapse-free survival (RFS) at 12 months
Time frame: Throughout the study period, at 12 months from the start of treatment
Overall survival (OS)
Time frame: Throughout the study period, at 12 months from the start of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Josep Maria Piulats, M.D., Ph.D. contact
Josep Maria Piulats, M.D., Ph.D. study chair
Institut Catala d'Oncologia (ICO) Hospitalet
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tebentafusp in people with Mestastatic Uveal Melanoma, run by Grupo Español Multidisciplinar de Melanoma at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Spain, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Federico Nepote (934344412, investigacion@mfar.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response (pCR) rate (time frame: Throughout the study period, at 7 months (+/- 1 month) from the start of treatment]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.