HLA-A*0201 Positive Cells PresentPhase 2NCT06942442
A Phase II Trial of Tebentafusp in HLA-A*02:01 Positive Patients With Advanced Clear Cell Sarcoma
A Phase 2 study testing Physician's Choice and Tebentafusp in people with HLA-A*0201 Positive Cells Present and Clear Cell Sarcoma (CCS), run by Sarcoma Alliance for Research through Collaboration at 4 sites in 2 countries.
Trial summary
This is a multi-center, open label, phase II study of tebentafusp in patients with unresectable or metastatic clear cell sarcoma (CCS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HLA-A*0201 Positive Cells Present, Clear Cell Sarcoma (CCS)
- What is being tested?
- Physician's Choice and Tebentafusp
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 22 Oct 2025to 1 Oct 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 2 countries
United States3 sites, 3 recruiting
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Seth Pollack, MD, 312-695-1102, cancer@northwestern.edu
- Recruiting
University of Southern California - Norris Cancer Center
Los Angeles, California, 90033
Sandy Tran, 323-365-8985, Sandy.tran@med.usc.edu
Mark Agulnik, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Sandra D'Angelo, MD, 646-888-4159, SARC045@sarctrials.org
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Marsden
London
Sarcoma Research Team, 44 207 808 23, rmh-tr.sarcoma.trials@nhs.net
About this study
This is a multi-center, open label, phase II study of tebentafusp in patients with unresectable or metastatic clear cell sarcoma (CCS).
Read the detailed description
This will be a multi-center, open label, phase II study of tebentafusp in patients with unresectable or metastatic CCS. Patients who screen positive for HLA-A*02:01 and meet the eligibility requirements will be treated with weekly tebentafusp. Radiographic assessment via CT or MR (where CT is not feasible or per the investigator's discretion) will occur at baseline and every subsequent 6 weeks through 48 weeks, and then every 9 weeks thereafter. Patients will be treated until progression of disease or unacceptable toxicity. All patients treated with tebentafusp will undergo mandatory research biopsies at baseline and on-treatment (week 6), if it is safe and feasible to do so. Serial peripheral blood samples for correlative analysis will be collected at baseline and at various time points on treatment.
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.
- Being tested
- Physician's Choice, Tebentafusp
- 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
- Medical subject headings
- Sarcoma, Clear Cell, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physician's ChoiceDrug
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.
TebentafuspDrug
Patients who screen positive for HLA-A*02:01 and meet the eligibility requirements will be treated with weekly tebentafusp
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Physician's Choice |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 5.5 months
Secondary outcomes (4)
Progression-Free Survival
To determine the PFS, in this population at months 3 and 5. Progression-free survival (PFS) defined as the time from study entry to disease relapse, disease progression, or death from any cause, using iRECIST. Patients without an event will be censored at the time of last disease follow-up.
Measured: Approximately 5 years
Estimate Overall Survival
To estimate the overall survival (OS) in patients who are HLA-A*02:01-positive with metastatic or unresectable clear cell sarcoma and treated with tebentafusp. Overall survival, defined as the time from study entry to death from any cause. Patients who are alive at the time of analysis will be censored at the date of last follow-up.
Measured: Approximately 5 years
Objective Response Rate
To estimate the objective response rate (ORR) in patients who are HLA-A*02:01-positive with metastatic or unresectable clear cell sarcoma and treated with tebentafusp, according to iRECIST. Objective tumor response, defined as achievement of nadir response of complete response (CR) or partial response (PR) by iRECIST without prior progression any time during protocol therapy.
Measured: Approximately 5 years
Duration of Response
To estimate the duration of response (DoR) in this population. DoR can be defined as the measurement of time from the start of treatment response to disease progression or death
Measured: Approximately 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2025
- Study start22 Oct 2025
- Primary completion1 Oct 2030 (estimated)
- Study completion1 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HLA-A*0201 Positive Cells PresentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sarcoma Alliance for Research through Collaboration
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06942442
- Sponsor's protocol ID
- SARC045
- Status last verified
- Oct 2025
- First submitted
- 21 Mar 2025
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Tebentafusp in HLA-A*02:01 Positive Patients With Advanced Clear Cell Sarcoma
- ClinicalTrials.gov ID
- NCT06942442
- Acronym / sponsor ID
- SARC045
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Sarcoma Alliance for Research through CollaborationUniversity, hospital or other
- Collaborators
- Royal Marsden NHS Foundation Trust, Memorial Sloan Kettering Cancer Center
- Study start
- 22 Oct 2025 (actual)
- Primary completion
- 1 Oct 2030 (estimated)
- Study completion
- 1 Oct 2030 (estimated)
- First posted
- 24 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, open label, phase II study of tebentafusp in patients with unresectable or metastatic clear cell sarcoma (CCS).
Detailed description
This will be a multi-center, open label, phase II study of tebentafusp in patients with unresectable or metastatic CCS. Patients who screen positive for HLA-A*02:01 and meet the eligibility requirements will be treated with weekly tebentafusp. Radiographic assessment via CT or MR (where CT is not feasible or per the investigator's discretion) will occur at baseline and every subsequent 6 weeks through 48 weeks, and then every 9 weeks thereafter. Patients will be treated until progression of disease or unacceptable toxicity. All patients treated with tebentafusp will undergo mandatory research biopsies at baseline and on-treatment (week 6), if it is safe and feasible to do so. Serial peripheral blood samples for correlative analysis will be collected at baseline and at various time points on treatment.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tebentafusp | Experimental | Drug: TebentafuspTebentafusp 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. |
| Physician's choice arm | Active comparator | Drug: Physician's ChoicePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Physician's ChoicePatients 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 arm |
| TebentafuspPatients who screen positive for HLA-A*02:01 and meet the eligibility requirements will be treated with weekly tebentafusp | Drug | Tebentafusp |
Primary outcome
Measure Disease Response
Time frame: Approximately 5.5 months
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.
4 secondary outcomes
Progression-Free Survival
Time frame: Approximately 5 years
Estimate Overall Survival
Time frame: Approximately 5 years
Objective Response Rate
Time frame: Approximately 5 years
Duration of Response
Time frame: Approximately 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Physician's Choice and Tebentafusp in people with HLA-A*0201 Positive Cells Present and Clear Cell Sarcoma (CCS), run by Sarcoma Alliance for Research through Collaboration at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact SARC Office ((734) 930-7600, SARC045@sarctrials.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure Disease Response (time frame: Approximately 5.5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.