Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma

NCT03070392 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IMCgp100-202
• Study Type: interventional
• Target: 378
• Locations: 14 countries
• Sites: 57

Brief 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.

Conditions

Uveal Melanoma

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

Outcome Measures

Primary Outcomes (1)

• Efficacy: Overall Survival

  Overall survival is defined as the time from randomization to date of death due to any cause.

  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 assessed from informed consent through 90 days after end of treatment, up to 36 months.

• Efficacy: Progression Free Survival (PFS)

  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

  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)

  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

  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.

Study Arms (2)

IMCgp100 (tebentafusp, Kimmtrak)

EXPERIMENTAL

Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)

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

Drug: Dacarbazine; Biological: Ipilimumab; Biological: Pembrolizumab

Interventions

IMCgp100 BIOLOGICAL

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

IMCgp100 (tebentafusp, Kimmtrak)

Dacarbazine DRUG

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

Also known as: DTIC-Dome, DTIC, DIC, Imidazole Carboxamide

Investigator's Choice

Ipilimumab BIOLOGICAL

Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments

Also known as: Yervoy

Investigator's Choice

Pembrolizumab BIOLOGICAL

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

Also known as: Keytruda

Investigator's Choice

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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 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
• 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

Sponsors & Collaborators

• Immunocore Ltd: lead

Study Sites (57)

UCLA Medical Center

Los Angeles, California, 90024, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Byers Eye Institute, Stanford University

Palo Alto, California, 94303, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Portland Providence Medical Center

Portland, Oregon, 97213, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

Saint Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center

Adelaide, South Australia, 5000, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

Institut Roi Albert II Cliniques Universitaires St-Luc

Brussels, Belgium

Location

Universite Catholique de Louvain Centre du Cancer, Medical Oncology

Brussels, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, M5G 2M9, Canada

Location

Centre Atoine Lacassagne

Nice, 6189, France

Location

Institut Curie

Paris, 75005, France

Location

Universitaetsklinikum Koeln Dermatologie und Venerologie

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Charite - Campus Benjamin Franklin

Berlin, 12200/12203, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

University Hospital Essen

Essen, Germany

Location

University of Hamburg

Hamburg, 20246, Germany

Location

Nationales Centrum für Tumorerkrankungen

Heidelberg, 69120, Germany

Location

Klinik und Poliklinik für Dermatologie und Allergologie

Munich, 80337, Germany

Location

Fondazione ICCRS

Milan, 20133, Italy

Location

Istituto Nazionale Tumori - IRCCS Fondazione "G. Pascale" - UOC Melanoma, Immunoterapia Oncologica e Terapie Innovative

Naples, 80131, Italy

Location

LUMC Medical Oncology

Leiden, 2333, Netherlands

Location

Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology

Moscow, 115478, Russia

Location

Federal State Budget Institution National Medical Research Center of Oncology

Saint Petersburg, 197758, Russia

Location

Institut Catala d'Oncologia (ICO) - L'Hospitalet

L'Hospitalet de Llobregat, ES-Spain, 08908, Spain

Location

Hospital Universitario La Paz

Madrid, ES-Spain, 28046, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, ES-Spain, 15706, Spain

Location

Hospital Universitario General de Valencia

Valencia, ES-Spain, 46014, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

University of Zurich Hospital

Zurich, 8091, Switzerland

Location

Dnipropetrovsk State Medical Academy

Dnipro, 49102, Ukraine

Location

Kyiv Munitipal Hospital

Kyiv, 02094, Ukraine

Location

Uzhhorod Central City Clinical Hospital

Uzhhorod, 8800, Ukraine

Location

Mount Vernon Cancer Centre

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

The Clatterbridge Cancer Centre

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Related Publications (2)

• Hassel 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.

  PMID: 37870955 DERIVED

• Nathan 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.

  PMID: 34551229 DERIVED

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

Dacarbazine; Ipilimumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Immunocore, Ltd

clinicaltrials@immunocore.com

1-844-IMMUNO-1

Study Officials

• Immunocore Medical Information

  Immunocore Ltd

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: March 3, 2017
• Study Start: October 16, 2017
• Primary Completion: October 13, 2020
• Study Completion: September 17, 2025
• Last Updated: March 17, 2026
• Results First Posted: September 14, 2021

Record last verified: 2026-03

Locations

UA (3); AU (3); DE (7); RU (2); CH (1); FR (2); NL (1); BE (2); IT (2); GB (3); ES (5); US (23); CA (2); PL (1)