Neoadjuvant Tebentafusp for Uveal Melanoma

NCT06414590 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: iRISID-2023-2369JT 33504
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Locally Advanced Unresectable Uveal Melanoma

Keywords

Neoadjuvant Tebentafusp; Uveal Melanoma; Primary Uveal Melanoma; Neoadjuvant IMCgp100; gp100 peptide-HLA-directed CD3 T cell engager; HLA-A*02:01; KIMMTRAK®; Tebentafusp-tebn; IMCgp100; radioactive plaque therapy; enucleation; radioactive plaque; fine-needle aspiration; circulating tumor-derived DNA; Phase II; advanced primary uveal melanoma; Simon's two stage design

Outcome Measures

Primary Outcomes (1)

• Regression of primary uveal melanoma after Tebentafusp treatment in 20% of treated patients.

  Regression is defined as ≥ 20% reduction in tumor volume. All estimates of rates will be presented with corresponding 95% exact confidence intervals. For regression rate, the method of Atkinson and Brown will be used to allow for the two-stage design.

  3 months post-eye treatment

Secondary Outcomes (3)

• Incidence of adverse events (AEs)

  Up to 5 years

• Detection of plasma circulating tumor-derived deoxyribonucleic acid (ctDNA) and correlation of antitumor response

  22 months

• Detection of aqueous humor ctDNA and correlation of antitumor response

  22 months

Other Outcomes (3)

• Assessment of visual acuity loss at baseline (prior to Tebentafusp treatment), prior to plaque brachytherapy, and 3) following plaque brachytherapy (after resolution of any radiation side effects/edema).

  22 months

• Change in radiation dose to the fovea.

  22 months

• Enucleation vs plaque brachytherapy post-treatment

  22 months

Study Arms (1)

Neoadjuvant Tebentafusp in Patients Locally Advanced, Unresectable Primary Uveal Melanoma

EXPERIMENTAL

Tebentafusp administration: 20mcg on Day 1, 30mcg on Day 8, 68 mcg on Day 15, and weekly doses of 68 mcg thereafter. Eye evaluations including clinical examination, ophthalmic ultrasound, optical coherence tomography, and wide-angle fundus imaging will be performed at baseline, Cycle 1 day 1, Cycle 1 day 8, Cycle 2 day 1, prior to definitive treatment for primary uveal melanoma (post-Tebentafusp), and at post-eye treatment evaluation at 3 months. Additionally optical coherence tomography angiography, autofluorescence, fluorescein angiography and MRI orbit will be performed at baseline, post-tebentafusp, and at post-eye treatment evaluation. Blood circulating tumor-derived DNA will be performed at baseline, Cycle 2 day 1, post-Tebentafusp, and at post-eye treatment evaluation at 3 months. Primary eye tumor biopsy (collected by fine-needle aspiration) and aqueous circulating tumor-derived DNA will be performed at baseline and post-Tebentafusp.

Drug: Tebentafusp-Tebn

Interventions

Tebentafusp-Tebn DRUG

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.

Also known as: KIMMTRAK®, IMCgp100, gp100 peptide-HLA-directed CD3 T cell engager

Neoadjuvant Tebentafusp in Patients Locally Advanced, Unresectable Primary Uveal Melanoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient age ≥ 18 years of age at the time of informed consent.
• Ability to provide and understand written informed consent prior to any study procedures.
• Willingness to undergo tumor biopsies at baseline and post-Tebentafusp treatment.
• Treatment naïve primary uveal melanoma with T3 or T4 category tumor size that are surgically unresectable (other than complete enucleation of eye).
• No surgical indication to completely remove the tumor without enucleation.
• Clinically or cytologically confirmed primary uveal melanoma.
• Participants must be HLA-A\*02:01 positive.
• Predicted life expectancy of at least 12 weeks as estimated by investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
• All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to first administration of study drug.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Symptomatic uveal melanoma that requires immediate ophthalmological intervention such as enucleation.
• Evidence of metastatic disease.
• Previous treatment with Tebentafusp.
• Patients with any out-of-range laboratory values defined as:
• Serum creatinine \> 1.5 x upper limit of normal (ULN) and/or creatinine clearance (calculated using Cockcroft-Gault Formula, or measured) \< 50 mL/minute
• Albumin \< 3.0 g/dl
• Total bilirubin \>1.5 mg/dL (or 1.3 x ULN). Patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator.
• Alanine aminotransferase \> 1.5 x ULN
• Aspartate aminotransferase \> 1.5 x ULN
• Absolute neutrophil count \< 1.0 x 109 /L
• Absolute lymphocyte count \< 0.5 x 109 /L
• Platelet count \< 100 x 109 /L
• Hemoglobin \< 9.0 g/dL
• Uncorrectable abnormal potassium, magnesium, corrected calcium or phosphate abnormality of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) \> grade 1

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Immunocore Ltd: collaborator

Study Sites (2)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Uveal Melanoma

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Rino Seedor, MD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rino Seedor, MD

CONTACT

215-955-8874; Rino.Seedor@Jefferson.edu

Rino Seedor, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2024
• First Posted: May 16, 2024
• Study Start: September 5, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): March 1, 2032
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)