Recruiting

Phase 2

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

Sponsor:

Sarcoma Alliance for Research through Collaboration

Code:

NCT06942442

Conditions

HLA-A*0201 Positive Cells Present

Clear Cell Sarcoma (CCS)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Physician's Choice

Tebentafusp

Study Details

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)

Study ID

NCT06942442

Start date

Oct 22, 2025

Status verified date

Oct, 2025

Completion date

Oct 1, 2030

Anticipated

Primary completion date

Oct 1, 2030

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria

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

Exclusion Criteria:

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
Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type
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
History of pneumonitis that required corticosteroid treatment or current pneumonitis
Ongoing requirement for intermittent or continuous oxygen supplementation
History of colitis or inflammatory bowel disease
Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary)
Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass
Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM- CSF, M-CSF) ≤ 2 weeks prior to start of study drug. An erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the patient is not red blood cell transfusion dependent
Women who are pregnant or nursing/breastfeeding. Where pregnancy is defined as the state of a female after conception and until the termination of gestation.
Women of childbearing potential who are sexually active with a non- sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment (defined in Section 7.2.3), and must agree to continue using such precautions for 6 months after the final dose of investigational product: cessation of birth control after this point should be discussed with a responsible physician.
Male patients must be surgically sterile or use double barrier contraception methods from enrollment through treatment and for 6 months following administration of the last dose of study drug

Study Design

Enrollment

47 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Tebentafusp

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.

active comparator: Physician's choice arm

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.

Interventions

Physician's Choice

Tebentafusp

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

Primary outcome measure

Measure Disease Response [ Time Frame: Approximately 5.5 months ]

Central Contacts and Locations

Central contacts

SARC Office

(734) 930-7600 SARC045@sarctrials.org

Locations

University of Southern California - Norris Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Sandy Tran

323-365-8985 Sandy.tran@med.usc.edu

Principal Investigator:

Mark Agulnik, MD

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Sandra D'Angelo, MD

646-888-4159 SARC045@sarctrials.org

More Information

Sponsor

Sarcoma Alliance for Research through Collaboration

Last update posted

Dec 26, 2025

Last verified

Oct, 2025

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-27. This information was provided to ClinicalTrials.gov by Sarcoma Alliance for Research through Collaboration on 2025-12-26. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.