NCT06414590

Neoadjuvant Tebentafusp for Uveal Melanoma

Neoadjuvant Tebentafusp in Patients With Locally Advanced, Unresectable Primary Uveal Melanoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 19 (estimated)
• Sponsor: Thomas Jefferson University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, single arm, phase II clinical trial of neoadjuvant Tebentafusp (KIMMTRAK®) in patients with locally advanced primary uveal melanoma. Patients must be HLA-A\*02:01 with large, surgically unresectable (other than complete enucleation of the eye) primary uveal melanoma. The efficacy of this treatment will be assessed with the Simon's two stage design. The choice of design is guided by a desire to stop the trial early if the actual regression rate of primary uveal melanoma is 1% or lower.

Detailed description

This is an investigator-initiated, Phase II trial evaluating neoadjuvant treatment for locally advanced, unresectable primary uveal melanoma with Tebentafusp. Given the success of Tebentafusp in the metastatic setting, we are interested in utilizing Tebentafusp in the neoadjuvant setting. Limited clinical research data suggest that Tebentafusp might accumulate in primary uveal melanoma and result in regression of primary uveal melanoma. This clinical trial will explore this possibility for patients with large and unresectable primary uveal melanoma. Changes in primary UM after Tebentafusp treatment and eye toxicity related to treatment will be monitored with ophthalmologic ultrasound, Optical coherence tomography (OCT) and clinical examination. Primary eye tumor biopsy pre-Tebentafusp and post-Tebentafusp treatment will also be performed by fine-needle aspiration. Blood and aqueous humor circulating tumor-derived DNA will also be measured as a potential biomarker for response. We will consider regression of the primary uveal melanoma by a 20% reduction in tumor volume a meaningful endpoint for this early phase clinical study. Reduction in volume by 20% could result in a proportion of patients who had planned enucleation prior to therapy to become suitable for plaque brachytherapy (exploratory endpoint). The efficacy of this combination treatment will be assessed using the Simon's two stage design \[Optimal Design\]. The trial is carried out in two stages. In stage I, a total number of 8 patients will be accrued. If there are 0 responses (at least a 20% reduction in tumor volume) among these 8 patients, further enrollment of patients may be stopped. Otherwise, an additional 11 patients will be accrued in stage II, resulting in a total sample size of 19. If there are 2 or more responses among these 19 patients, we reject the null hypothesis and claim that the treatment is promising. PRIMARY OBJECTIVE: To assess the efficacy of neoadjuvant Tebentafusp in patients with large surgically unresectable (other than complete enucleation of the eye) primary uveal melanoma. SECONDARY OBJECTIVES: 1. To assess the local (eye) and systemic toxicity with Tebentafusp treatment. 2. To investigate the usefulness of ctDNA as a biomarker for response. EXPLORATORY OBJECTIVES: 1. To assess sight preservation. 2. To assess the change in radiation dose to the fovea. OUTLINE: Participants may be screened at Wills Eye Hospital before being consented and treated at Thomas Jefferson University. Patients receive tebentafusp intravenously (IV) over 15-20 minutes on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within 28 days of their last dose of tebentafusp, patients undergo standard of care (SOC) primary eye treatment (plaque radiotherapy or eye enucleation), as decided by their treating physician. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening, ophthalmic ultrasound, optical coherence tomography (OCT), wide-angle fundus imaging, OCT angiography (OCTA), fluorescein angiography, orbit magnetic resonance imaging (MRI), and collection of blood samples throughout the trial, undergo biopsy and collection of aqueous humour samples at screening and on study, and undergo abdominal MRI and chest and pelvis computed tomography (CT) at screening and during follow up. After completion of primary eye treatment, patients are followed up at 3 months and then for survival for up to 5 years.

Conditions

• Locally Advanced Unresectable Uveal Melanoma

Interventions

Type	Name	Description
DRUG	Tebentafusp-Tebn	Tebentafusp will be administered as follows: 20mcg on Day 1, 30mcg on Day 8, 68 mcg on Day 15, and weekly doses of 68 mcg thereafter.

Timeline

• Start date: 2025-09-05
• Primary completion: 2027-08-01
• Completion: 2032-03-01
• First posted: 2024-05-16
• Last updated: 2026-04-14

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study