Neoadjuvant Tebentafusp in Patients With Metastatic Uveal Melanoma
ConditionMestastatic Uveal Melanoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGrupo Español Multidisciplinar de Melanoma
About this trial
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. 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. Which is the efficacy of tebentafusp used as a single agent to maintain disease control and delay relapse / progression. 3. 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%).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have histologically confirmed metastatic uveal melanoma with Human leukocyte antigen-A*0201 positive determined by local assay.
Minor resection (i.e., less than a hemihepatectomy)
Major resection (i.e., hemihepatectomy or extended hepatectomy)
Bilobar resection (including atypical resection).
Disqualifiers
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 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.
Trial design
Design model
Single group
Treatments tested in this trial
Tebentafusp
DrugPatients 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.
Treatment groups
19 Participants
are divided into 1 treatment groupGroup A: Neoadjuvant TebentafuspExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
Throughout the study period, at 7 months (+/- 1 month) from the start of treatment]Secondary outcomes
1
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.
Time frame
Throughout the study period, at 6 months from the start of treatment2
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.
Time frame
Throughout the study period, at 6 months from the start of treatment3
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.
Time frame
Throughout the study period, approximate average of 24 months since the start of treatment4
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.
Time frame
Throughout the study period, at 6 months from the start of treatmentSponsors and contacts
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Source ClinicalTrials.gov