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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070392
Recruitment Status : Active, not recruiting
First Posted : March 3, 2017
Last Update Posted : October 29, 2020
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

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.

Condition or disease Intervention/treatment Phase
Uveal Melanoma Biological: IMCgp100 Drug: Dacarbazine Biological: Ipilimumab Biological: Pembrolizumab Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 378 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 16, 2017
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
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

Drug: 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
Other Names:
  • DTIC-Dome
  • DTIC
  • DIC
  • Imidazole Carboxamide

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

Biological: Pembrolizumab
Pembrolizumab is to be administered at 2 mg/kg IV infusion over 30 minutes every 3 weeks until confirmed disease progression or unacceptable toxicity
Other Name: Keytruda




Primary Outcome Measures :
  1. Overall survival defined as the time from patient inclusion to date of death due to any cause [ Time Frame: Survival status will be assessed every 3 months from randomization until death, assessed up to 40 months. ]

Secondary Outcome Measures :
  1. Safety defined as the number of patients with treatment emergent adverse events, laboratory abnormalities, ECG changes, and/or physical examination findings [ Time Frame: Safety will be assessed from informed consent through 90 days after end of treatment ]
  2. Efficacy: Objective response rate (ORR) defined as the proportion of patients achieving an objective response (RECIST v1.1) by Independent Central Review [ Time Frame: ORR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months ]
  3. Efficacy: Duration of response (DOR) defined as the time from first documented objective response (RECIST v1.1) by Independent Central Review until the date of documented disease progression [ Time Frame: DOR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months ]
  4. Efficacy: Progression free survival (PFS) defined as the time from randomization to the date of progression (RECIST v1.1) by Independent Central Review or death due to any cause [ Time Frame: PFS will be assessed every 3 months from randomization until disease progression or death, assessed up to 40 months ]
  5. Efficacy: Disease control rate (DCR) defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1) by Independent Central Review. [ Time Frame: DCR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months ]
  6. Quality-of-Life: General health status will be assessed using the EQ-5D,5L questionnaire [ Time Frame: : EQ-5D,5L will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until death, assessed up to 40 months ]
  7. Quality-of-Life: Health related quality of life will be assessed using EORTC QLQ-C30 questionnaire [ Time Frame: EORTC QLQ-C30 will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until disease progression, assessed up to 40 months ]
  8. Pharmacokinetics (IMCgp100 Arm only): Area under the plasma concentration-time curve (AUC) [ Time Frame: AUC will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months ]
  9. Pharmacokinetics (IMCgp100 Arm only): The maximum observed plasma drug concentration after single dose administration (Cmax) [ Time Frame: Cmax will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months ]
  10. Pharmacokinetics (IMCgp100 Arm only): The time to reach maximum plasma concentration (Tmax) [ Time Frame: Tmax will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks ]
  11. Pharmacokinetics (IMCgp100 Arm only): The elimination half-life (t1/2) [ Time Frame: t1/2 will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks ]
  12. Pharmacokinetics (IMCgp100 Arm only): To assess the 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 40 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070392


Locations
Show Show 59 study locations
Sponsors and Collaborators
Immunocore Ltd
Investigators
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Study Director: Mohammed Dar Immunocore Ltd
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Responsible Party: Immunocore Ltd
ClinicalTrials.gov Identifier: NCT03070392    
Other Study ID Numbers: IMCgp100-202
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: October 29, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Immunocore Ltd:
Melanoma
Uveal Cancer
IMCgp100
Immunotherapy
Additional relevant MeSH terms:
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Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Pembrolizumab
Ipilimumab
Dacarbazine
Imidazole
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors