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

NCT ID: NCT03070392

Last Updated: 2025-08-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 378 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-16
• Study Completion Date: 2025-12-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMCgp100 (tebentafusp, Kimmtrak)

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

Group Type: EXPERIMENTAL

IMCgp100

Intervention Type: 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

Investigator's Choice

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

Group Type: ACTIVE_COMPARATOR

Dacarbazine

Intervention Type: 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

Ipilimumab

Intervention Type: BIOLOGICAL

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

Pembrolizumab

Intervention Type: 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

Interventions

IMCgp100

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

Intervention Type: BIOLOGICAL

Dacarbazine

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

Intervention Type: DRUG

Ipilimumab

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

Intervention Type: BIOLOGICAL

Pembrolizumab

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

Intervention Type: BIOLOGICAL

Other Intervention Names

DTIC-Dome; DTIC; DIC; Imidazole Carboxamide; Yervoy; Keytruda

Eligibility Criteria

Inclusion Criteria

1. Male or female participants age ≥ 18 years of age at the time of informed consent

2. Ability to provide and understand written informed consent prior to any study procedures

3. Histologically or cytologically confirmed metastatic UM

4. 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.

5. HLA A*0201 positive by central assay

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening

7. Participants have measurable disease or non-measurable disease according to RECIST v1.1

8. 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

1. Out-of-range laboratory values

2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies

3. Clinically significant cardiac disease or impaired cardiac function,

4. 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

5. 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

6. Known history of human immunodeficiency virus infection (HIV). Testing for HIV status is not necessary unless clinically indicated

7. 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

8. 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

9. 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

10. 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

11. History of adrenal insufficiency

12. History of interstitial lung disease

13. History of pneumonitis that required corticosteroid treatment or current pneumonitis

14. History of colitis or inflammatory bowel disease

15. 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)

16. 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

17. 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

18. 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)

19. 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

20. 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

21. Participant who are in an institution due to official or judicial order.

22. 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.

23. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immunocore Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Immunocore Medical Information

Role: STUDY_DIRECTOR

Immunocore Ltd

Locations

UCLA Medical Center

Los Angeles, California, United States

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Byers Eye Institute, Stanford University

Palo Alto, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

The University of Chicago Medicine

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Health System

Durham, North Carolina, United States

The Ohio State University

Columbus, Ohio, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Portland Providence Medical Center

Portland, Oregon, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Houston Methodist Cancer Center

Houston, Texas, United States

Saint Vincents Hospital

Darlinghurst, New South Wales, Australia

Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center

Adelaide, South Australia, Australia

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia

Institut Roi Albert II Cliniques Universitaires St-Luc

Brussels, , Belgium

Universite Catholique de Louvain Centre du Cancer, Medical Oncology

Brussels, , Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

Princess Margaret Cancer Centre

Toronto, , Canada

Centre Atoine Lacassagne

Nice, , France

Institut Curie

Paris, , France

Universitaetsklinikum Koeln Dermatologie und Venerologie

Cologne, North Rhine-Westphalia, Germany

Charite - Campus Benjamin Franklin

Berlin, , Germany

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

University Hospital Essen

Essen, , Germany

University of Hamburg

Hamburg, , Germany

Nationales Centrum für Tumorerkrankungen

Heidelberg, , Germany

Klinik und Poliklinik für Dermatologie und Allergologie

Munich, , Germany

Fondazione ICCRS

Milan, , Italy

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

Napoli, , Italy

LUMC Medical Oncology

Leiden, , Netherlands

Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie

Warsaw, , Poland

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

Moscow, , Russia

Federal State Budget Institution National Medical Research Center of Oncology

Saint Petersburg, , Russia

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

L'Hospitalet de Llobregat, ES-Spain, Spain

Hospital Universitario La Paz

Madrid, ES-Spain, Spain

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, ES-Spain, Spain

Hospital Universitario General de Valencia

Valencia, ES-Spain, Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

University of Zurich Hospital

Zurich, , Switzerland

Dnipropetrovsk State Medical Academy

Dnipro, , Ukraine

Kyiv Munitipal Hospital

Kyiv, , Ukraine

Uzhhorod Central City Clinical Hospital

Uzhhorod, , Ukraine

Mount Vernon Cancer Centre

Northwood, Middlesex, United Kingdom

The Clatterbridge Cancer Centre

Bebington, Wirral, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Italy; Netherlands; Poland; Russia; Spain; Switzerland; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37870955 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34551229 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IMCgp100-202

Identifier Type: -

Identifier Source: org_study_id