Uveal MelanomaPhase 2NCT06070012
Tebentafusp in HLA-A*0201 Positive Previously Untreated Metastatic Uveal Melanoma
A Phase 2 study testing Tebentafusp in people with Uveal Melanoma, run by Diwakar Davar at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- Tebentafusp
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 4 sitesUnited States
- Study dates
- 18 Aug 2025to 30 Sep 2030
- Phase
- Phase 2
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
- Histologically or cytologically confirmed untreated metastatic uveal melanoma (mUM).
- HLA-A0201 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.
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- 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.
- Prior surgical resection of oligometastatic disease is allowed.
- Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative setting in patients with localized disease.
- Life expectancy of >6 months as estimated by the investigator.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening.
- Patients have measurable disease according to RECIST v.1.1.
- 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 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.
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- 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.
- NOTE: Patients with HIV who are stably controlled on highly active antiretroviral therapy (HAART) therapy with a low HIV viral load may be enrolled. In these instances, stable control is defined as HAART compliant with a CD4 count of ≥200 cells/μL, and low viral load is defined as <200 copies/mL on tests done during Screening.
- Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following:
- Completely resected carcinoma in situ of any type, resected basal cell and squamous cell carcinomas.
- Malignancies that were treated curatively and have not recurred within 2 years prior to study treatment;
- Any malignancy considered to be indolent that has never required therapy Sponsor-Investigator evaluation.
- Any medical condition that would, in the judgment of the Sponsor-Investigator, 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.
- NOTE: Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable.
- History of symptomatic autoimmune disease including:
- Interstitial lung disease.
- Pneumonitis requiring corticosteroid treatment or current pneumonitis.
- Colitis or inflammatory bowel disease. NOTE: However, patients with a history of autoimmune disease who are currently on physiologic hormone repletion (prednisone or equivalent of 10mg or less) and are otherwise asymptomatic may be enrolled.
- 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.
- Pregnant, likely to become pregnant, or lactating women (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 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.
- Receipt of live or attenuated vaccinations 2 weeks prior to starting study therapy. Patients may receive vaccinations on treatment.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
University of Colorado Cancer Center
Aurora, Colorado, 80045
Kathy Prinz, CRC, 303-724-9815, kathy.prinz@cuanschutz.edu
Sarah Bunting, CRC, 303-724-9815, sarah.bunting@cuanschutz.edu
- Recruiting
The Ohio State University
Columbus, Ohio, 43210
John John McCarthy, 614-685-0808, John.McCarthy@osumc.edu
Jacob Nelson, 614-688-5821, Jacob.Nelson@osumc.edu
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Amy Rose, RN, BSN, 412-647-8587, kennaj@upmc.edu
Samantha Berton, RN, BSN, bertonsf@upmc.edu
- Recruiting
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Jamie Manganti, BSN, RN, 202-687-3937, jm3821@georgetown.edu
Bethelhem Mekonen, BSN, RN, 202-444-0241, bam159@georgetown.edu
About this study
Official title: Phase II Open-label, Multi-center Study of Tebentafusp in HLA-A*0201 Positive Previously Untreated Metastatic Uveal Melanoma (mUM) With Integrated Circulating Tumor DNA (ctDNA) Biomarker (TARGET-tebe)
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.
Read the detailed description
Uveal Melanoma (UM) is a rare type of melanoma (3.1% of all melanoma incidence, approximately 4000 cases globally per year) with an incidence of 5.3-10.9 cases per million individuals. Despite its rare incidence rate, UM is the most frequent primary intraocular malignancy of the adult eye that affects the vascular layers of the eye (iris, ciliary body, and choroid). UM has a high incidence of metastases, predominantly to the liver, because of the lack of significant lymphatic traffic out of the eye and predominant hematogenous spread.
Tebentafusp has been studied in four clinical studies including IMCgp100-01 (NCT01211262; ≥2L cutaneous and uveal melanoma), IMCgp100-102 (NCT02570308; ≥2L uveal melanoma), IMCgp100-201 (NCT02535078; PD-1 naïve and PD-1 R/R cutaneous melanoma), and IMCgp100-202 (NCT03070392; 1L uveal melanoma vs. physicians' choice chemotherapy). Based on early first-in-human (FIH) studies, tebentafusp 68 mcg was identified as the RP2D; with an intra- patient escalation regimen (20 mcg at C1D1 and 30 mcg at C1D8) and the dose escalated at C1D15. This dose was subsequently evaluated in a recently completed phase -II trial - IMC-p100-202 - that randomized 378 treatment-naïve, HLA-A*0201 positive patients with advanced uveal melanoma on a 2-to-1 ratio to tebentafusp (n = 252) or investigator's choice (IC) of dacarbazine, ipilimumab, or pembrolizumab (n = 126). Based on the data from the IMCgp100-202 study, the current approved dose of tebentafusp is a fixed starting dose of 20mcg (C1D1), followed by 30 mcg (C1D8) and 68mcg at C1D15 and beyond.
The primary outcome measure was updated to reference a tumor-informed ctDNA assay to align with the protocol language and description of the planned analysis.
- Conditions
- Uveal Melanoma
- Being tested
- Tebentafusp
- Keywords
- CD8+ TILs, tumor-associated macrophages (TAMs), PD-L1 (B7- H1), PD-L2 (B7-DC)
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TebentafuspDrug
Also called Kimmtrak
An anti-cancer medication used to treat uveal melanoma. Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager.
| Study group | Role | What they receive |
|---|---|---|
| Tebentafusp (IMCgp100) | Experimental | Dose: 20mcg W1D; 30mcg W2D1; 68mcg W3D1and subsequent doses
Frequency: Weekly on D1 of 12-week cycles Receives: Drug: Tebentafusp |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ctDNA response
ctDNA response (defined as ≥0.3 log reduction) in ctDNA-evaluable patients as measured by tumor-informed ctDNA assay.
Measured: At Baseline, at Week 10 of each 12-week cycle, Up to 24 months]
Secondary outcomes (9)
Objective Response Rate (ORR)
ORR as assessed imRECIST. Percentage of patients with partial response (PR) or complete response (CR) to the treatment. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Up to 36 months
Overall Survival (OS)
Median length of time from start of treatment that patients remain alive.
Measured: Up to 5 years
1-year Overall Survival (OS)
The percentage of patients alive at one year after start of treatment.
Measured: At one year (post start of treatment)
2-year Overall Survival (OS)
The percentage of patients alive at two years after start of treatment.
Measured: At two years (post start of treatment)
3-year Overall Survival (OS)
The percentage of patients alive at three years after start of treatment.
Measured: At three years (post start of treatment)
Progression-free Survival (PFS)
Median number of months from start of treatment to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: Up to 5 years
6-month Progression-free Survival (PFS)
Percentage of patients without disease progression or death from any cause at six months after start of treatment. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: At 6 months (post start of treatment)
1-year Progression-free Survival (PFS)
Percentage of patients without disease progression or death from any cause at one year after start of treatment. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: At one year (post start of treatment)
2-year Progression-free Survival (PFS)
Percentage of patients without disease progression or death from any cause at two years after start of treatment. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Measured: At two years (post start of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2023
- Study start18 Aug 2025
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal MelanomaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Diwakar Davar
- Sponsor type
- University, hospital or other
- Collaborators
- Immunocore Ltd
- Responsible party
- Sponsor-investigator, Diwakar Davar, University of Pittsburgh
- Investigators
- Diwakar Davar, MD, PhD, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06070012
- Sponsor's protocol ID
- HCC 22-165
- Status last verified
- Sep 2026
- First submitted
- 20 Sep 2023
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No