A Phase II Trial of Tebentafusp in HLA-A*02:01 Positive Patients With Advanced Clear Cell Sarcoma

NCT06942442 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SARC045
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-center, open label, phase II study of tebentafusp in patients with unresectable or metastatic clear cell sarcoma (CCS).

Conditions

HLA-A*0201 Positive Cells Present; Clear Cell Sarcoma (CCS)

Keywords

sarcoma; Tebentafusp; HLA-A*0201 Positive; HLA-A*02:01-negative; HMB-45+ clear cell sarcoma; Unresectable clear cell sarcoma; metastatic clear cell sarcoma

Outcome Measures

Primary Outcomes (1)

• Measure Disease Response

  To estimate the population of HLA-A\*02:01-positive patients with metastatic or unresectable clear cell sarcoma and treated with tebentafusp who are progression free at 24 weeks. PFS (progression-free survival) will be determined using iRECIST.

  Approximately 5.5 months

Secondary Outcomes (4)

• Progression-Free Survival

  Approximately 5 years

• Estimate Overall Survival

  Approximately 5 years

• Objective Response Rate

  Approximately 5 years

• Duration of Response

  Approximately 5 years

Other Outcomes (1)

• Progression-Free Survival and Objective Response Rate

  Approximately 5 years

Study Arms (2)

Tebentafusp

EXPERIMENTAL

Tebentafusp will be administered via IV infusion on Days 1, 8, and 15 of a 21-day cycle. Treatment on C1D1 will be 20mcg, treatment on C1D8 will be 30 mcg. After this initial dosing period, beginning at C1D15 and beyond, patients are eligible to receive the full dose of 68 mcg. 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.

Drug: Tebentafusp

Physician's choice arm

ACTIVE COMPARATOR

Patients who are HLA-A\*02:01-negative and ineligible to receive tebentafusp will be prospectively enrolled onto a separate study arm and treated with physicians' choice of treatment. They will also be radiographically assessed at the same schedule as patients treated with tebentafusp, if feasible, and kept on this treatment arm until progression of disease or unacceptable toxicity on the physicians' choice regimen.

Drug: Physician's Choice

Interventions

Physician's Choice DRUG

Patients who are HLA-A\*02:01-negative and ineligible to receive tebentafusp will be prospectively enrolled onto a separate study arm and treated with physicians' choice of treatment. They will also be radiographically assessed at the same schedule as patients treated with tebentafusp, if feasible, and kept on this treatment arm until progression of disease or unacceptable toxicity on the physicians' choice regimen.

Physician's choice arm

Tebentafusp DRUG

Patients who screen positive for HLA-A\*02:01 and meet the eligibility requirements will be treated with weekly tebentafusp

Tebentafusp

Eligibility Criteria

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

You may qualify if:

• Age 18 years
• Histologically confirmed diagnosis of HMB-45+ clear cell sarcoma which is unresectable and/or metastatic
• HLA-A\*02:01 positive
• ECOG Performance Status of £ 2 at screening
• At least one site of measurable disease on CT/MRI scan as defined by RECIST v 1.1 criteria. Baseline imaging must be performed within 28 days of Cycle 1 Day 1 of study.
• Adequate organ function within 28 days of Day 1 of study defined as:
• Absolute Neutrophil Count (ANC) ≥ 1.5
• Platelets ≥ 75
• ALT and AST ≤ 2.5 x institutional upper limit of normal (ULN) or ≤ 5.0 x institutional ULN if considered due to tumor
• Alkaline phosphatase ≤ 2.5 x institutional ULN unless considered due to tumor
• Serum bilirubin ≤ 1.5 x institutional ULN. NOTE: Patients with elevated bilirubin secondary to Gilbert's disease are eligible to participate in the study
• Serum creatinine ≤ 1.5 x institutional ULN or 24-hour creatinine clearance ≥ 50 ml/min (calculated creatinine clearance using Cockroft formula is acceptable)
• Written, voluntary informed consent
• Patients must demonstrate progression of disease by RECIST 1.1 within 6 months of study enrollment. Newly diagnosed patients with unresectable or metastatic disease and only one baseline scan are eligible to screen and enroll.
• 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

You may not qualify if:

• History of sever hypersensitivity reaction (e.g. 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.
• 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. Patients with brain metastases are eligible if lesions have been treated with localized therapy and there is no evidence of progression for at least 4 weeks by MRI prior to the first dose of study drug
• Active infection requiring systemic antibiotic therapy. 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 human immunodeficiency virus (HIV) infection (defined as CD4 count \< 200 and/or a detectable viral load). Testing for HIV status is not necessary unless clinically indicated
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection
• Any medical condition that would, in the investigator's or Sponsor's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
• Patients receiving systemic steroid therapy or any other immunosuppressive medication at any dose level, as these may interfere with the mechanism of action of study treatment. Local steroid therapies (e.g., otic, ophthalmic, intra-articular or inhaled medications) are acceptable
• History of adrenal insufficiency
• Participants with clinically significant pulmonary disease or impaired lung function, including any of the following:
• An oxygen saturation of \< 92% on room air, measured by pulse oximeter
• History of interstitial lung disease

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• Royal Marsden NHS Foundation Trust: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (2)

University of Southern California - Norris Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma, Clear Cell; Sarcoma

Interventions

tebentafusp

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

SARC Office

CONTACT

(734) 930-7600; SARC045@sarctrials.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: April 24, 2025
• Study Start: October 22, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: December 26, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)