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A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With 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: NCT02570308
Recruitment Status : Active, not recruiting
First Posted : October 7, 2015
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

Tracking Information
First Submitted Date  ICMJE October 6, 2015
First Posted Date  ICMJE October 7, 2015
Last Update Posted Date July 31, 2019
Study Start Date  ICMJE February 2016
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
  • Phase 1 Recommended phase 2 dose of the intra-patient escalation regimen (RP2D-IE) [ Time Frame: 1 years ]
  • 2. Phase 2: Objective response rate by RECIST 1.1 assessed by independent central review [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2015)
Recommended phase 2 dose of the intra-patient escalation regimen (RP2D-IE) [ Time Frame: 2 years ]
Change History Complete list of historical versions of study NCT02570308 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 25, 2018)
  • Objective response rate (Phase 1) [ Time Frame: 2 years ]
  • Progression free survival [ Time Frame: 2 years ]
  • Overall survival [ Time Frame: 2 years ]
  • Duration of response [ Time Frame: 2 years ]
  • Time to response [ Time Frame: 2 years ]
  • Minor response rate [ Time Frame: 2 years ]
  • Number of treatment dose interruptions and reductions [ Time Frame: 2 years ]
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: 2 years ]
  • Area under the plasma concentration-time curve (AUC) [ Time Frame: 3 weeks ]
  • The maximum observed plasma drug concentration after single dose administration (Cmax) [ Time Frame: 2 years ]
  • The time to reach maximum plasma concentration (Tmax) [ Time Frame: 3 weeks ]
  • The elimination half-life (t1/2) [ Time Frame: 3 weeks ]
  • Incidence of anti-IMCgp100 antibody formation [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2015)
  • Objective response rate [ Time Frame: 2 years ]
  • Progression free survival [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma
Official Title  ICMJE A Phase I/II Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Using the Intra-patient Escalation Dosing Regimen in Patients With Advanced Uveal Melanoma
Brief Summary IMCgp100-102 is a Phase I/II study of the weekly intra-patient escalation dose regimen with IMCgp100 as a single agent in patients with metastatic uveal melanoma (mUM). According to this regimen, all patients in the trial will receive 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation will commence at the third weekly dose at C1D15. The Phase I testing of the intra-patient escalation dosing regimen is designed to achieve a higher exposure and maximal plasma concentration of IMCgp100 after doses at Cycle 1 Day 15 (C1D15) and thereafter .
Detailed Description

This is a Phase I/II clinical study of IMCgp100 in patients with advanced uveal melanoma.

This is a Phase I/II study of IMCgp100 administered on a weekly basis with an intra-patient escalation dosing regimen. The intra-patient escalation occurs at the third weekly dose on Cycle 1 Day 15 (C1D15). According to this regimen, all patients in the trial will receive 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation will commence at the third weekly dose at C1D15 with the goal to achieve a long-term dosing regimen at a dose higher than that identified for the straight weekly dosing regimen (RP2D-QW). The dose escalation will identify the intra-patient escalation regimen (RP2D-IE).

The Phase I portion of the study was a standard 3+3 dose escalation design. The Phase 1 portion of the study is now complete. The recommended Phase II dose of the intra-patient escalation dose regimen (RP2D-IE) was identified and the 2 expansion cohorts in metastatic uveal melanoma will be completed. The cohorts will enroll patients with metastatic uveal melanoma and are defined based on prior therapy The expansion portion will enroll approximately 150 patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Uveal Melanoma
Intervention  ICMJE Drug: IMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific TCR fused to anti-CD3
Study Arms  ICMJE
  • Experimental: Dose escalation
    Dose escalation cohorts of the intra-patient escalation regimen. This arm is closed
    Intervention: Drug: IMCgp100
  • Experimental: Dose expansion
    Dose expansion cohort with the recommended phase 2 dose of the intra-patient dose escalation regimen
    Intervention: Drug: IMCgp100
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 26, 2018)
150
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2015)
40
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 diagnosis of metastatic uveal melanoma (mUM)
  4. Surgically sterile patients or patients of child-bearing potential who agree to use highly effective methods of contraception during study dosing and for 6 months after last dose of study drug
  5. Life expectancy of >3 months as estimated by the investigator
  6. Human leukocyte antigen (HLA)-A*0201 positive
  7. ECOG Performance Status of 0 or 1 at Screening
  8. Patients in Phase 1 must have disease (measurable or non-measurable acceptable) according to Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 criteria
  9. Patients in Phase 2 must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 criteria
  10. Patients in Phase 2 expansion cohort A will have experienced disease progression with 1 systemic treatment containing a checkpoint inhibitor. Any prior liver directed therapy is acceptable.
  11. Patients in Phase 2 expansion cohort B will have experienced disease progression with 1 or 2 prior lines of therapy, including up to 1 prior line of liver-directed therapy

Exclusion Criteria:

  1. 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. Asymptomatic and adequately treated CNS metastases are not exclusionary
  2. History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies
  3. Patient with any out-of-range laboratory values defined as:

    • Serum creatinine > 1.5 x upper limit of normal (ULN) and/or creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 mL/min
    • Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
    • ALT > 3 x ULN
    • AST > 3 x ULN
    • Absolute neutrophil count < 1.0 x 10^9/L
    • Absolute lymphocyte count < 0.5 x 10^9/L (Phase 1 and Phase 2 Cohort A); absolute lymphocyte count < 1.0 x 10^9/L (Phase 2 Cohort B)
    • Platelet count < 75 x 10^9/L
    • Hemoglobin < 8 g/dL
    • Potassium, magnesium, corrected calcium or phosphate abnormality of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) > grade 1
  4. 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
    • QTcF >470 msec on screening ECG or congenital long QT syndrome
    • Acute myocardial infarction or unstable angina pectoris < 6 months prior to Screening
  5. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy before Screening
  6. Known history of HIV infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulations
  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 or if required by local regulations
  8. Patients receiving systemic treatment with systemic steroid therapy or any other immunosuppressive medication at any dose level that would interfere with the action of the study drugs in the opinion of the investigator
  9. 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
  10. Any medical condition that would, in the investigator'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
  11. Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic or immunotherapy agents that can present with major delayed toxicity (eg, anti-CTLA-4), 4 weeks is indicated as washout period
  12. Presence of NCI CTCAE ≥ grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ NCI CTCAE grade 3) due to prior cancer therapy
  13. Chronic systemic corticosteroid use (ie, prednisone > 10 mg QD or the equivalent); treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone ≤ 10 mg QD or the equivalent, and patients must have no history of adrenal crisis. Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable
  14. 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)
  15. 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
  16. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GMCSF, M-CSF) ≤ 2 weeks prior to start of study drug. Patients must have completed therapy with any hematopoietic colony-stimulating factor at least 2 weeks before the first dose of study drug is given. 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
  17. 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)
  18. Patients with adrenal insufficiency or patients currently requiring chronic, systemic corticosteroid therapy at any dose for longer than 2 weeks. Local steroid therapies (eg, otic, ophthalmic, intraarticular, or inhaled medications) are acceptable
  19. Patients may not have been included in any prior IMCgp100 trial, regardless of treatment cohort
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02570308
Other Study ID Numbers  ICMJE IMCgp100-102
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Immunocore Ltd
Study Sponsor  ICMJE Immunocore Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Immunocore Ltd
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP