Tebentafusp-tebn With LDT in Metastatic UM

Part of paid clinical trials in Philadelphia, Pennsylvania.

Sponsor
Thomas Jefferson University
Study ID
NCT06626516
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Metastatic Uveal Melanoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tebentafusp-Tebn — DRUG
    Dosing: All patients enrolled in this study will receive treatment with tebentafusp-tebn based on the approved step-up dosing regimen of 20 mcg on C1D1, 30 mcg on C1D8, then 68 mcg weekly beginning on C1D15 and thereafter. This escalated dose administered at C1D15 will be the dose used for the remainder of the treatment period unless dose reduction is implemented for toxicity. Beginning with C1D8, tebentafusp-tebn will be administered on the scheduled day (± 2 days), and consecutive infusions of tebentafusp-tebn must be administered at least 5 days apart.
  • GM-CSF (Sargramostim) — DRUG
    Recombinant human GM-CSF (Sargramostim, Leukine®, Sanofi US) 1,500mg will be mixed with ethiodized oil (Ethiodol®). The GM-CSF/ethiodized oil mixture will be injected selectively into one of the hepatic lobes, followed by infusion of gelatin sponge particles to achieve the stasis of blood flow. This will repeat every 4 weeks.
  • BCNU — DRUG
    Patients will be treated with hepatic artery infusion of 300mg BCNU (1,3-bis \[2-chloroethyl\]-1-nitrosourea, Carmustine) dissolved in ethiodized oil followed by embolization with gelatin sponge particles \[TACE with BCNU 300mg\]; every 4 weeks +/- 7 days in the case of either bilobar or unilobar metastasis

Study Details

This study is a multicenter, open label phase I/ II trial to assess the safety and clinical efficacy of tebentafusp-tebn in combination with liver-directed therapies in HLA-A\*0201 positive patients with metastatic uveal melanoma. In Part 1 of the study, the Prinicipal Investigator will investigate the safety and efficacy of tebentafusp-tebn in combination with hepatic IE in patients with a low to moderate hepatic disease burden. In Part 2, the study will investigate the efficacy of tebentafusp-tebn in combination with TACE in patients with bulky hepatic disease.

Key Dates

Start date
Oct 15, 2025
Status verified
Jun 2026
Primary completion
Oct 31, 2030
Completion
Aug 31, 2032

Study Design

Enrollment
109 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1A: Safety Lead-in
    Phase I safety lead-in followed by a phase II trial with 6-month PFS rate as the preliminary efficacy endpoint. All patients will receive a 4-week induction course of tebentafusp-tebn alone (Cycle 1) using the approved step-up dosing regimen. Should the 4th dose be tolerated well as an outpatient, patients will receive their first IE treatment on Cycle 2 week 1 followed by continued weekly tebentafusp-tebn on weeks 2, 3, and 4 of Cycle 2 (See Figure 1). Patients will not receive tebentafusp-tebn concurrently with their first IE treatment during Week 1 of Cycle 2. Should Cycle 2 be well tolerated, patients may receive both tebentafusp-tebn and IE on Week 1 of subsequent
  • Active Comparator: Part 1B: Combination
    If the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone, with PFS as the primary endpoint. Patients randomized to tebentafusp-tebn + IE arm will be treated as Part 1A.
  • Active Comparator: Part 1B: Tebentafusp-tebn alone
    If the safety and preliminary efficacy in Part 1A are met, we will then proceed with a randomized phase II trial. 52 patients will be randomized in a 2:1 ratio to receive tebentafusp-tebn in combination with hepatic IE or tebentafusp-tebn alone, with PFS as the primary endpoint. Patients randomized to tebentafusp-tebn alone will receive weekly treatment using the approved step-up dosing regimen.
  • Active Comparator: Part 2: Efficacy of Combo
    To assess the efficacy of tebentafusp-tebn in sequence with TACE in HLA-A\*0201-positive patients with metastatic uveal melanoma to the liver

Primary Outcome Measure

Part 1A: Safety lead-in [ Time Frame: From when the patient receives the first study treatment to 7 days (for non-serious AEs) or 30 days (for SAEs) after completion of study treatment or withdrawal from the study. ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Thomas Jefferson UniversityPhiladelphiaPennsylvania19107
Rino Seedor, MD
[email protected]
215-600-9151
Rino Seedor, MD (PRINCIPAL_INVESTIGATOR)
Marlana Orloff, MD (SUB_INVESTIGATOR)

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