Uveal MelanomaPhase 2NCT03070392
Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma
A Phase 2 study testing IMCgp100, Dacarbazine and Ipilimumab in people with Uveal Melanoma, run by Immunocore Ltd at 57 sites in 14 countries.
Trial summary
To evaluate the overall survival of HLA-A*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- IMCgp100, Dacarbazine and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 378 participants
- Where
- 57 sitesin 14 countries
- Study dates
- 16 Oct 2017to 17 Sep 2025
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants age ≥ 18 years of age at the time of informed consent
- Ability to provide and understand written informed consent prior to any study procedures
- Histologically or cytologically confirmed metastatic UM
- Must meet the following criteria related to prior treatment:
- No prior systemic therapy in the metastatic or advanced setting including chemotherapy, immunotherapy, or targeted therapy
- No prior regional, liver-directed therapy including chemotherapy, radiotherapy, or embolization
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- Prior surgical resection of oligometastatic disease is allowed
- Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative setting in participants with localized disease. Participants may not be re-treated with an Investigator's Choice therapy that was administered as adjuvant or neoadjuvant treatment. Additionally, participants who have received nivolumab as prior adjuvant/neoadjuvant treatment should not receive pembrolizumab as Investigator's Choice therapy.
- HLA A*0201 positive by central assay
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening
- Participants have measurable disease or non-measurable disease according to RECIST v1.1
- 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
- Out-of-range laboratory values
- History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
- Clinically significant cardiac disease or impaired cardiac function,
- 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. Participants with brain metastases are eligible if lesions have been treated with localized therapy and there is no evidence of PD for at least 4 weeks by magnetic resonance imaging (MRI) prior to the first dose of study drug
- Active infection requiring systemic antibiotic therapy. Participants requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug
- Known history of human immunodeficiency virus infection (HIV). Testing for HIV status is not necessary unless clinically indicated
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- 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 participants participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results
- Participants receiving systemic steroid therapy or any other systemic immunosuppressive medication at any dose level, as these may interfere with the mechanism of action of study treatment. Local steroid therapies (eg, otic, ophthalmic, intra-articular, or inhaled medications) are acceptable
- History of adrenal insufficiency
- History of interstitial lung disease
- History of pneumonitis that required corticosteroid treatment or current pneumonitis
- 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 (e.g., 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 (defined in Section 6.7), 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. Highly effective methods of contraception are described in Section 6.7
- Male participants 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
- Participant who are in an institution due to official or judicial order.
- Participant who are the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in the conduct of the study.
- Contraindication for treatment with Investigator's Choice alternatives (dacarbazine, ipilimumab and pembrolizumab) as per applicable labelling. Participant may have a contraindication to 1 or 2 of the choices if he/she is a candidate for dosing with at least 1 Investigator's Choice and meets all other study eligibility criteria.
Trial locations and contacts
57 sites in 14 countries.
57 sites in 14 countries
United States23 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
University of Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263
Northwestern University
Chicago, Illinois, 60611
The University of Chicago Medicine
Chicago, Illinois, 60637
The Ohio State University
Columbus, Ohio, 43210
Duke University Health System
Durham, North Carolina, 27710
Houston Methodist Cancer Center
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
UCLA Medical Center
Los Angeles, California, 90024
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Oklahoma
Oklahoma City, Oklahoma, 73104
Byers Eye Institute, Stanford University
Palo Alto, California, 94303
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Portland Providence Medical Center
Portland, Oregon, 97213
California Pacific Medical Center
San Francisco, California, 94115
Washington University School of Medicine
St Louis, Missouri, 63110
Germany7 sites
Charite - Campus Benjamin Franklin
Berlin, 12200/12203
Universitaetsklinikum Koeln Dermatologie und Venerologie
Cologne, North Rhine-Westphalia, 50937
Universitätsklinikum Carl Gustav Carus
Dresden, 01307
University Hospital Essen
Essen
University of Hamburg
Hamburg, 20246
Nationales Centrum für Tumorerkrankungen
Heidelberg, 69120
Klinik und Poliklinik für Dermatologie und Allergologie
Munich, 80337
Spain5 sites
Institut Catala d'Oncologia (ICO) - L'Hospitalet
L'Hospitalet de Llobregat, ES-Spain, 08908
Hospital Universitario La Paz
Madrid, ES-Spain, 28046
Hospital Clínico Universitario de Santiago de Compostela
Santiago de Compostela, ES-Spain, 15706
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario General de Valencia
Valencia, ES-Spain, 46014
Australia3 sites
Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center
Adelaide, South Australia, 5000
Saint Vincents Hospital
Darlinghurst, New South Wales, 2010
Peter MacCallum Cancer Center
Melbourne, Victoria, 3000
Ukraine3 sites
Dnipropetrovsk State Medical Academy
Dnipro, 49102
Kyiv Munitipal Hospital
Kyiv, 02094
Uzhhorod Central City Clinical Hospital
Uzhhorod, 8800
United Kingdom3 sites
The Clatterbridge Cancer Centre
Bebington, Wirral, CH63 4JY
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Mount Vernon Cancer Centre
Northwood, Middlesex, HA6 2RN
Belgium2 sites
Institut Roi Albert II Cliniques Universitaires St-Luc
Brussels
Universite Catholique de Louvain Centre du Cancer, Medical Oncology
Brussels
Canada2 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Princess Margaret Cancer Centre
Toronto, M5G 2M9
Italy2 sites
Fondazione ICCRS
Milan, 20133
Istituto Nazionale Tumori - IRCCS Fondazione "G. Pascale" - UOC Melanoma, Immunoterapia Oncologica e Terapie Innovative
Naples, 80131
Russia2 sites
Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology
Moscow, 115478
Federal State Budget Institution National Medical Research Center of Oncology
Saint Petersburg, 197758
Poland1 site
Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie
Warsaw, 02-781
About this study
Official title: A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared With Investigator Choice in HLA-A*0201 Positive Patients With Previously Untreated Advanced Uveal Melanoma
To evaluate the overall survival of HLA-A*0201 positive adult patients with previously untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine, ipilimumab, or pembrolizumab.
Read the detailed description
This Phase II study is designed to evaluate the safety and efficacy of IMCgp100 compared with Investigator's Choice (dacarbazine, ipilimumab or pembrolizumab) in HLA-A*0201 positive adult patients with advanced UM treated in the first line setting with no prior systemic or liver-directed chemo-, radio- or immune-therapy administered in the advanced setting (prior surgical resection of liver metastases and adjuvant systemic therapy are acceptable). Comparison of the IMCgp100 efficacy results in this Phase II study will be made with the concurrently randomized arm (Investigator's Choice) with a primary endpoint of overall survival (OS) and secondary efficacy endpoints of progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and disease control rate (DCR).
- Conditions
- Uveal Melanoma
- Being tested
- IMCgp100, Dacarbazine, Ipilimumab, Pembrolizumab
- Keywords
- Melanoma, Uveal Cancer, IMCgp100, Immunotherapy, Tebentafusp, Ocular Melanoma, Eye Melanoma, Uveal Melanoma, Gp100, TCR, Dacarbazine, Ipilimumab, Pembrolizumab, Bispecific T cell receptor fusion protein, ImmTAC, Immune mobilizing monoclonal T cell receptor against cancer, Kimmtrak
- Medical subject headings
- Uveal Melanoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMCgp100Biological
IMCgp100 is to be administered at 20 mcg cycle 1 day1, then 30 mcg cycle 1 day 8, then 68 mcg cycle 1 day 15 and weekly thereafter by IV infusion over 15 minutes until confirmed disease progression or unacceptable toxicity
DacarbazineDrug
Also called DTIC-Dome, DTIC, DIC, Imidazole Carboxamide
Dacarbazine is to be administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity
IpilimumabBiological
Also called Yervoy
Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments
PembrolizumabBiological
Also called Keytruda
Pembrolizumab is to be administered at 2 mg/kg IV infusion up to a maximum of 200 mg administered Intravenously over 30 minutes every 3 weeks or 200 mg fixed dose administered intravenously every 3 weeks where approved locally until confirmed disease progression or unacceptable toxicity
| Study group | Role | What they receive |
|---|---|---|
| IMCgp100 (tebentafusp, Kimmtrak) | Experimental | Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100) Receives: Biological: IMCgp100 |
| Investigator's Choice | Active comparator | 1 of 3 Investigator's Choice options: Systemic Dacarbazine
1 of 3 Investigator's Choice options: Systemic Ipilimumab
1 of 3 Investigator's Choice options: Systemic Pembrolizumab Receives: Drug: Dacarbazine; Biological: Ipilimumab; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: Overall Survival
Overall survival is defined as the time from randomization to date of death due to any cause.
Measured: From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.
Secondary outcomes (10)
Safety: Number of Participants With Treatment Emergent Adverse Events
Safety was defined as the number of participants with treatment emergent adverse events, including laboratory abnormalities, ECG changes, and/or physical examination findings.
Measured: Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.
Efficacy: Progression Free Survival (PFS)
Progression free survival (PFS) is defined as the time from randomization to the date of progression (RECIST v1.1) or death due to any cause.
Measured: PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.
Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores
General health status was assessed using the EQ-5D,5L questionnaire, which includes five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 scoring levels, where 1 indicates a better health state (no problems) and 3 indicates a worse health state. A positive change indicates improvement.
Measured: EQ-5D,5L was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)
The EQ-5D VAS score records the participant's self-rated health on a vertical visual analogue scale, with 0 being the worst imaginable health state and 100 being the best imaginable health state. A positive change indicates improvement.
Measured: EQ-5D,5L VAS was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status
Global health status and quality of life was assessed using the EORTC QLQ-C30 questionnaire. The score range for the EORTC QLQ-C30 is from 0 to 100, with higher scores indicating better functioning and better global health status and health-related quality of life. A positive change indicates improvement.
Measured: EORTC QLQ-C30 was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
Pharmacokinetics (PK): Tebentafusp Concentration
Serum PK concentrations of tebentafusp were collected over time.
Measured: PK concentrations were assessed at pre-dose, end of infusion and anytime in the 12 to 24 hour window after completion of the infusion in Cycle 1 on Days 1, 8 and 15.
Efficacy: Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the proportion of patients achieving an objective response (RECIST v1.1).
Measured: ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.
Efficacy: Duration of Response (DOR)
Duration of response (DOR) is defined as the time from first documented objective response (RECIST v1.1) until the date of documented disease progression.
Measured: DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.
Efficacy: Disease Control Rate (DCR)
Disease control rate (DCR) is defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1)
Measured: DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.
Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation
Measured: Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start16 Oct 2017
- Primary completion13 Oct 2020
- Study completion17 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 378 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immunocore Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Immunocore Medical Information, Study director, Immunocore Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03070392
- Sponsor's protocol ID
- IMCgp100-202
- Status last verified
- Mar 2026
- First submitted
- 14 Feb 2017
- Last updated
- 17 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
Piperno-Neumann S, Rutkowski P, Hassel JC, Butler MO, Schlaak M, Sullivan RJ, Dummer R, Kirkwood JM, Sacco JJ, Shoushtari AN, Piulats JM, Salama AKS, Orloff MM, Joshua AM, Ochsenreither S, Gastaud L, Curti BD, Demidov LV, Milhem MM, Chmielowski B, Kendra KL, Ascierto PA, Bernicker EH, Carvajal RD, Collins L, Lockwood S, Patel JM, Hamid OA, Baurain JF, Nathan PD. Five-year survival with tebentafusp in metastatic uveal melanoma. Ann Oncol. 2026 May 19:S0923-7534(26)00879-3. doi: 10.1016/j.annonc.2026.05.695. Online ahead of print.
PubMed 42162665Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain JF, Schlaak M, Butler MO, Sullivan RJ, Dummer R, Kirkwood JM, Orloff M, Sacco JJ, Ochsenreither S, Joshua AM, Gastaud L, Curti B, Piulats JM, Salama AKS, Shoushtari AN, Demidov L, Milhem M, Chmielowski B, Kim KB, Carvajal RD, Hamid O, Collins L, Ranade K, Holland C, Pfeiffer C, Nathan P. Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2023 Dec 14;389(24):2256-2266. doi: 10.1056/NEJMoa2304753. Epub 2023 Oct 21.
PubMed 37870955Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021 Sep 23;385(13):1196-1206. doi: 10.1056/NEJMoa2103485.
PubMed 34551229