Tebentafusp in HLA-A*0201 Positive Previously Untreated Metastatic Uveal Melanoma

NCT06070012 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 22-165
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase II open-label, single-arm, multi-center study of tebentafusp in HLA- A\*0201 positive previously untreated (1L) untreated metastatic uveal melanoma (mUM) with an integrated circulating tumor DNA (ctDNA) biomarker.

Conditions

Uveal Melanoma

Keywords

CD8+ TILs; tumor-associated macrophages (TAMs); PD-L1 (B7- H1); PD-L2 (B7-DC)

Outcome Measures

Primary Outcomes (1)

• Change in ctDNA response

  ctDNA response (defined as ≥0.3 log reduction) in ctDNA-evaluable patients as measured using Signatera assay.

  At Baseline, at Week 10 of each 12-week cycle, Up to 24 months]

Secondary Outcomes (9)

• Objective Response Rate (ORR)

  Up to 36 months

• Overall Survival (OS)

  Up to 5 years

• 1-year Overall Survival (OS)

  At one year (post start of treatment)

• 2-year Overall Survival (OS)

  At two years (post start of treatment)

• 3-year Overall Survival (OS)

  At three years (post start of treatment)

Study Arms (1)

Tebentafusp (IMCgp100)

EXPERIMENTAL

Dose: 20mcg W1D; 30mcg W2D1; 68mcg W3D1and subsequent doses Frequency: Weekly on D1 of 12-week cycles

Drug: Tebentafusp

Interventions

Tebentafusp DRUG

An anti-cancer medication used to treat uveal melanoma. Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager.

Also known as: Kimmtrak

Tebentafusp (IMCgp100)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed untreated metastatic uveal melanoma (mUM).
• HLA-A\*0201 genotype positive as assessed using a CLIA-certified blood typing method and confirmed by central review.
• If HLA-A status is not known, blood for HLA-A testing must be submitted during Screening, and HLA-A\*0201 positive status confirmed prior to enrollment using a CLIA- certified blood typing method.
• If the patient is known to be HLA-A\*0201 positive, this information must be provided in the Screening packet and centrally reviewed by treating PI and Sponsor-Investigator prior to enrollment.
• The following HLA testing methodologies are suitable to determine HLA-A\*0201 positivity:
• Multiplex real-time PCR based testing performed by entities including but not limited to Labcorp, and American Red Cross.
• HLA testing as part of peripheral blood molecular profiling technology including but not limited to Caris Life Sciences Molecular Profiling Technology.
• Patients be willing to undergo ctDNA assessment using Signatera assay.
• Have provided newly obtained core biopsy of a tumor lesion not previously irradiated.
• Adequate organ function on screening labs obtained within 4 weeks of Week 1 day 1
• Must meet the following criteria related to prior treatment:
• No prior systemic therapy in the metastatic or advanced setting including chemotherapy, or targeted therapy.
• NOTE: Patients must be tebentafusp naïve.
• NOTE: Patients must not have received prior PD-1, CTLA-4, LAG-3 directed Immune Checkpoint Inhibitor therapy delivered in the adjuvant, and/or neoadjuvant settings unless such therapy was received \>6 months prior initial diagnosis of mUM.
• No prior regional, liver-directed therapy including chemotherapy, radiotherapy, or embolization.

You may not qualify if:

• History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies.
• Clinically significant cardiac disease or impaired cardiac function, including any of the following:
• 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.
• QTcF \> 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome.
• NOTE: If the initial automated QTcF interval is \> 470 msec at screening, for the purpose of determining eligibility, the mean QTcF, based on at least 3 ECGs obtained over a brief time interval (ie, within 30 minutes), should be manually determined by a medically qualified person.
• NOTE: Acute myocardial infarction or unstable angina pectoris \< 6 months prior to Screening.
• Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids within the prior 3 weeks to study Day 1.
• Presence of active brain metastases.
• NOTE: Patients with brain metastases are eligible if all lesions have been treated surgically and/or radiosurgically and there is no evidence of progression for at least 2 weeks by MRI prior to the first dose of study drug.
• NOTE: Patients with any evidence of leptomeningeal disease are excluded.
• Active infection requiring systemic antibiotic therapy.
• NOTE: Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug.
• Known history of uncontrolled active human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.
• NOTE: Testing for HIV, HBV and/or HCV is not necessary unless clinically indicated or the patient has a history of HBV/HCV and/or HIV infection.
• NOTE: Patients with curatively treated HBV and/or HCV infection may be enrolled. In these instances, HBV (quantitative HBV DNA) and/or HCV (quantitative HCV RNA) resolution must be documented using a quantitative viral load assay.

Sponsors & Collaborators

• Immunocore Ltd: collaborator
• Diwakar Davar: lead

Study Sites (3)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Uveal Melanoma

Interventions

tebentafusp

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

• Diwakar Davar, MD, PhD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Rose, RN, BSN

CONTACT

412-647-8587; kennaj@upmc.edu

Danielle L Bednarz, RN, BSN

CONTACT

4126231191; bertonsf@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine, Hematology/Oncology.

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: October 6, 2023
• Study Start: August 18, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)