Clinical Trial - NCT03070392

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

Active, not recruiting

Sponsor: Immunocore Ltd

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03070392

Protocol Info

Short Description: IMCgp100 VS investigator's choice in uveal melanoma
Long Description: A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared with Investigator’s Choice in HLA-A*0201 Positive Patients with Previously Untreated Advanced Uveal Melanoma
MGH Status: Open
Sponsor: Immunocore
Disease Program: Melanoma

Next Steps


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Purpose

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.
Condition Title Intervention Phase
Uveal Melanoma IMCgp100 Dacarbazine Ipilimumab Pembrolizumab Phase 2
Study Type Interventional
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

Primary Outcome Measures

Efficacy: Overall Survival [Time Frame: From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.] [Designated as safety issue: ]


Secondary Outcome Measures

Safety: Number of Participants With Treatment Emergent Adverse Events [Time Frame: Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.] [Designated as safety issue: ]

Efficacy: Progression Free Survival (PFS) [Time Frame: PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.] [Designated as safety issue: ]

Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores [Time Frame: 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 28 days.] [Designated as safety issue: ]

Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS) [Time Frame: 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 28 days.] [Designated as safety issue: ]

Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status [Time Frame: 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 28 days.] [Designated as safety issue: ]

Pharmacokinetics (PK): Tebentafusp Concentration [Time Frame: PK concentrations were assessed at pre-dose, end of infusion and 12-24 hours in Cycle 1 on Days 1, 8 and 15.] [Designated as safety issue: ]

Efficacy: Objective Response Rate (ORR) [Time Frame: ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.] [Designated as safety issue: ]

Efficacy: Duration of Response (DOR) [Time Frame: DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.] [Designated as safety issue: ]

Efficacy: Disease Control Rate (DCR) [Time Frame: DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.] [Designated as safety issue: ]

Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation [Time Frame: Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years.] [Designated as safety issue: ]

Estimated Enrollment: 378
Study Start Date: October 2017
Estimated Study Completion Date: March 2023
Estimated Primary Completion Date: October 2020
Arms Assigned Interventions

Experimental:IMCgp100

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

Active Comparator: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
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

Eligibility

Ages Eligible for Study: 99 Years-99 Years

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria

1. Male or female patients 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 patients with localized disease. Patients may not be re-treated with an Investigator's Choice therapy that was administered as adjuvant or neoadjuvant treatment. Additionally, patients 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. Life expectancy of > 3 months as estimated by the investigator

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

8. Patients have measurable disease or non-measurable disease according to RECIST v1.1

9. 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. Patient with any out-of-range laboratory values defined as:

  • Serum creatinine > 1.5 × upper limit of normal (ULN) and/or creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 mL/minute
  • Total bilirubin > 1.5 × ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN
  • Alanine aminotransferase > 3 × ULN
  • Aspartate aminotransferase > 3 × ULN
  • Absolute neutrophil count < 1.0 × 109/L
  • Absolute lymphocyte count < 0.5 × 109/L
  • Platelet count < 75 × 109/L
  • Hemoglobin < 8 g/dL

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

3. 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
  • QT interval corrected by Fridericia's formula (QTcF) > 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome. NOTE: If the initial automated QTcF 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

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. Patients 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. Patients 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 patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results

10. Patients 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 (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

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 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

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

22. Patients 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. Patient 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03070392

Locations

  • United States, California
    • UCLA Medical Center Los Angeles, California, United States, 90024
    • The Angeles Clinic and Research Institute Los Angeles, California, United States, 90025
    • Byers Eye Institute, Stanford University Palo Alto, California, United States, 94303
    • California Pacific Medical Center San Francisco, California, United States, 94115
  • United States, Colorado
    • University of Colorado Aurora, Colorado, United States, 80045
  • United States, Florida
    • University of Miami - Sylvester Comprehensive Cancer Center Miami, Florida, United States, 33136
  • United States, Georgia
    • Winship Cancer Institute of Emory University Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • Northwestern University Chicago, Illinois, United States, 60611
    • The University of Chicago Medicine Chicago, Illinois, United States, 60637
  • United States, Iowa
    • University of Iowa Iowa City, Iowa, United States, 52242
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115
  • United States, Missouri
    • Washington University School of Medicine Saint Louis, Missouri, United States, 63110
  • United States, New York
    • Roswell Park Cancer Institute Buffalo, New York, United States, 14263
    • Columbia University Medical Center New York, New York, United States, 10032
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, North Carolina
    • Duke University Health System Durham, North Carolina, United States, 27710
  • United States, Ohio
    • The Ohio State University Columbus, Ohio, United States, 43210
  • United States, Oklahoma
    • University of Oklahoma Oklahoma City, Oklahoma, United States, 73104
  • United States, Oregon
    • Portland Providence Medial Center Portland, Oregon, United States, 97213
  • United States, Pennsylvania
    • Thomas Jefferson University Hospital Philadelphia, Pennsylvania, United States, 19107
    • University of Pittsburgh Medical Center Pittsburgh, Pennsylvania, United States, 15232
  • United States, Texas
    • Houston Methodist Cancer Center Houston, Texas, United States, 77030
  • Australia, New South Wales
    • Saint Vincents Hospital Darlinghurst, New South Wales, Australia, 2010
  • Australia, South Australia
    • Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center Adelaide, South Australia, Australia, 5000
  • Australia, Victoria
    • Peter MacCallum Cancer Center Melbourne, Victoria, Australia, 3000
  • Belgium,
    • Institut Roi Albert II Cliniques Universitaires St-Luc Bruxelles, , Belgium,
  • Canada, Alberta
    • Cross Cancer Institute Edmonton, Alberta, Canada, T6G 1Z2
  • Canada,
    • Princess Margaret Cancer Centre Toronto, , Canada, M5G 2M9
  • France,
    • Centre Atoine Lacassagne Nice, , France, 6189
    • Institut Curie Paris, , France, 75005
  • Germany, Nordrhein Westfalen
    • Universitaetsklinikum Koeln Dermatologie und Venerologie Koeln, Nordrhein Westfalen, Germany, 50937
  • Germany,
    • Charite - Campus Benjamin Franklin Berlin, , Germany, 12200/12203
    • Universitätsklinikum Carl Gustav Carus Dresden, , Germany, 01307
    • University Hospital Essen Essen, , Germany,
    • University of Hamburg Hamburg, , Germany, 20246
    • Nationales Centrum für Tumorerkrankungen Heidelberg, , Germany, 69120
    • Klinik und Poliklinik für Dermatologie und Allergologie Munich, , Germany, 80337
  • Italy,
    • Fondazione ICCRS Milan, , Italy, 20133
    • Istituto Nazionale Tumori - IRCCS Fondazione "G. Pascale" - UOC Melanoma, Immunoterapia Oncologica e Terapie Innovative Napoli, , Italy, 80131
  • Netherlands,
    • LUMC Medical Oncology Leiden, , Netherlands, 2333
  • Poland,
    • Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie Warsaw, , Poland, 02-781
  • Russian Federation,
    • Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology Moscow, , Russian Federation, 115478
    • Federal State Budget Institution National Medical Research Center of Oncology Saint Petersburg, , Russian Federation, 197758
  • Spain, ES-Spain
    • Institut Catala d'Oncologia (ICO) - L'Hospitalet L'Hospitalet De Llobregat, ES-Spain, Spain, 08908
    • Hospital Universitario La Paz Madrid, ES-Spain, Spain, 28046
    • Hospital Clínico Universitario de Santiago de Compostela Santiago De Compostela, ES-Spain, Spain, 15706
    • Hospital Universitario General de Valencia Valencia, ES-Spain, Spain, 46014
  • Spain,
    • Hospital Universitario Virgen Macarena Sevilla, , Spain, 41009
  • Switzerland,
    • University of Zurich Hospital Zürich, , Switzerland, 8091
  • Ukraine,
    • Dnipropetrovsk State Medical Academy Dnipropetrovs'k, , Ukraine, 49102
    • Kyiv Munitipal Hospital Kyiv, , Ukraine, 02094
    • Uzhhorod Central City Clinical Hospital Uzhhorod, , Ukraine, 8800
  • United Kingdom, Middlesex
    • Mount Vernon Cancer Centre Northwood, Middlesex, United Kingdom, HA6 2RN
  • United Kingdom, Wirral
    • The Clatterbridge Cancer Centre Bebington, Wirral, United Kingdom, CH63 4JY
  • United Kingdom,
    • Beatson West of Scotland Cancer Centre Glasgow, , United Kingdom, G12 0YN

Sponsors and Collaborators

Immunocore Ltd

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03070392
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Immunocore Ltd:

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

Additional relevant MeSH terms:

Melanoma

Uveal Neoplasms

Pembrolizumab

Ipilimumab

Dacarbazine

Imidazole

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on October 14, 2021