TPS9596 Background: Uveal melanoma (UM) has a high rate of metastasis, most commonly to the liver. Tebentafusp-tebn (Tebe) is a first-in class immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC) that gained regulatory approval after it showed significantly improved overall survival (OS) compared to single-agent investigator’s choice in a pivotal randomized phase III trial. For patients with oligometastatic liver disease, liver-directed therapies (LDT) such as hepatic immunoembolization (IE) and chemoembolization (CE) have been used with success. LDT and Tebe may have therapeutic limitations when administered independently, but combining the two approaches is a potentially beneficial strategy that could provide both short-term hepatic disease control and long-term systemic disease control. Methods: This is an investigator-initiated, multicenter, open-label phase I/randomized phase II trial to assess the safety and clinical efficacy of Tebe in combination with LDT in HLA-A*02:01 positive patients with metastatic UM NCT06626516. In Part 1 of the study, we will investigate the safety and efficacy of Tebe + IE in patients with low to moderate hepatic disease burden (M1a or M1b disease with largest tumor ≤ 5 cm, AND 5cm, M1c disease, or >50% liver involvement). Patients must be 18 years or older, HLA-A*02:01 with metastatic UM in the liver. Extra-hepatic disease is allowed. Patients must be treatment naïve in the metastatic setting for Part 1 and must have no more than two prior lines of treatment (systemic or liver directed) for Part 2. Patients will receive Tebe at the approved step-up dosing regimen (20 mcg IV on C1D1, 30 mcg IV on C1D8, then 68 mcg on C1D15 and weekly thereafter). Patients in Part 1 will receive IE with GM-CSF 1500mcg every 4 weeks (starting at week 5) for the first four treatments and then 4 weeks as maintenance if clinically indicated. Part 1 has a phase I safety lead-in (Part 1A), followed by a phase II trial (Part 1B) where patients are randomized 2:1 to receive Tebe + IE or Tebe alone. Patients in Part 2 will receive CE with BCNU 300mg every 4 weeks for a total of 2 (unilobar disease) or 4 (bilobar disease) treatments followed by weekly Tebe. Eighteen patients, 52 patients, and 39 patients will be enrolled in Part 1A, Part 1B, and Part 2, respectively (total 109 patients). Primary endpoints for Part 1A is safety lead-in and 6-month progression-free survival (PFS), 6-month PFS for Part 1B, and 6-month PFS for Part 2. Secondary endpoints include overall response rate, liver-specific PFS, OS, and toxicity. Enrollment for Part 1A began in October 2025 at Thomas Jefferson University Hospital. Clinical trial information: NCT06626516 .
Seedor et al. (Thu,) studied this question.