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Phase 1b/2 Study of the Combination of IMCgp100 With Durvalumab and/or Tremelimumab in Cutaneous 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. Identifier: NCT02535078
Recruitment Status : Active, not recruiting
First Posted : August 28, 2015
Last Update Posted : April 14, 2021
MedImmune LLC
Information provided by (Responsible Party):
Immunocore Ltd

Tracking Information
First Submitted Date  ICMJE August 26, 2015
First Posted Date  ICMJE August 28, 2015
Last Update Posted Date April 14, 2021
Study Start Date  ICMJE November 2015
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
Phase 1b Number of dose-limiting toxicities [ Time Frame: 12 months ]
The number of dose-limiting toxicities (DLT) observed during the DLT observation period. DLT observation period for the Arms 1 to 3 Phase Ib cohorts will be the first 2 cycles of treatment (C1D1 until C2D28). The DLT observation period for Arm 4 Phase Ib will be from C1D22 to C2D14. A DLT is defined as an adverse event or abnormal laboratory value that occurs during the relevant DLT period which is assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications, occurs during the DLT Observation Period or is Grade 3 or higher per NCI CTCAE version 4.03, or as specified in the protocol.
Original Primary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
Progression-free survival [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2021)
  • Phase 2b Objective Response Rate [ Time Frame: 2 years ]
    Objective Response Rate (RECIST v1.1) Objective response rate, defined as the proportion of patients with a best response of CR or PR based on investigator assessment, as defined in RECIST v1.1.
  • Overall survival [ Time Frame: 2 years ]
    Time from the date of first dose until death due to any cause.
  • Safety: AEs and SAEs [ Time Frame: 2 years ]
    Safety incidence and severity of AEs and SAEs including changes in laboratory. parameters, vital signs, and electrocardiograms (ECG).
  • Safety: Tolerability [ Time Frame: 2 years ]
    Tolerability of study treatment will be assessed by summarizing the number of treatment dose interruptions and dose reductions.
  • Safety: Tolerability [ Time Frame: 2 years ]
    Dose interruptions
  • Safety: Tolerability [ Time Frame: 2 years ]
    Dose Reductions
  • Safety: Tolerability [ Time Frame: 2 years ]
    Dose Intensity
  • Serum Pharmacokinetics [ Time Frame: 2 years ]
    AUClast : Area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1)
  • Serum Pharmacokinetics [ Time Frame: 2 years ]
    AUCinf : The AUC from time zero to infinity (mass x time x volume-1)
  • Serum Pharmacokinetics [ Time Frame: 2 years ]
    Cmax : Maximum Plasma Concentration
  • Serum Pharmacokinetics [ Time Frame: 2 years ]
    Tmax: The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
  • Serum Pharmacokinetics [ Time Frame: 2 years ]
    t1/2 : Elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time)
  • Correlation of PD-L1 and gp100 [ Time Frame: 2 years ]
  • Progression Free Survival [ Time Frame: 2 years ]
    Correlation of gp100 and PD-L1 expression by immunohistochemistry evaluated in pre-treatment biopsies with anti-tumor activity.
  • Duration of Response [ Time Frame: 2 years ]
    Time from the date of first documented response until date of documented progression or death in the absence of disease progression. The median duration of response and corresponding 90% confidence interval will be presented.
  • Overall Survival [ Time Frame: 2 years ]
    Time from the date of first dose until death due to any cause. OS will be presented including all patients treated at the MTD or RP2D.
  • Time to Response [ Time Frame: 2 years ]
    Time from initiation of therapy to the time that an OR per RECISTv1.1 is achieved.
  • Disease Control Rate [ Time Frame: 2 years ]
    Proportion of patients with either a best response of PR or CR or with SD over 24 weeks after first dose in the study. The DCR and associated 90% confidence interval will be presented by treatment arm.
  • Formation of Anti-drug Antibodies [ Time Frame: 2 years ]
    Incidence of anti-IMCgp100, anti-durvalumab, and anti-tremelimumab antibody formation following multiple infusions of IMCgp100 alone and in combination with durvalumab and/or tremelimumab.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
  • Objective response rate [ Time Frame: 12 months ]
  • Overall 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 Phase 1b/2 Study of the Combination of IMCgp100 With Durvalumab and/or Tremelimumab in Cutaneous Melanoma
Official Title  ICMJE A Phase Ib/II Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 in Combination With Durvalumab (MEDI4736) or Tremelimumab or the Combination of Durvalumab and Tremelimumab Compared to IMCgp100 Alone in Patients With Advanced Melanoma
Brief Summary

This study is a Phase Ib/II, multi-center, open-label study of IMCgp100 as a single agent and in combination with durvalumab (MEDI4736) and/or tremelimumab in metastatic cutaneous melanoma. The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and to evaluate the anti-tumor activity of IMCgp100 in combination with durvalumab (MEDI4736, programmed death-ligand 1 [PD-L1] inhibitor), tremelimumab (CLTA-4 inhibitor), and the combination of durvalumab with tremelimumab compared to single-agent IMCgp100 alone. The study will enroll patients who have metastatic melanoma that is refractory to treatment with an anti-PD-1 inhibitor in the metastatic setting. This study will also evaluate the safety, tolerability, and anti-tumor activity of IMCgp100 monotherapy in patients with advanced non-uveal melanoma who progressed on prior PD-1 inhibitors approved for the treatment of advanced melanoma; patients with BRAF mutations must be refractory to approved BRAF-based therapy.

Recent biologic evidence indicates that optimal responses to programmed cell death-1 (PD-1) directed therapy require the presence of CD8+ T cells in the tumor microenvironment and thus therapies such as IMCgp100 that recruit these effector cells to the tumor may overcome pre-existing resistance to checkpoint blockade. This emerging biology of checkpoint inhibitor resistance suggests the combination of IMCgp100 with checkpoint inhibition may have enhanced activity in patients with pre-existing resistance.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Melanoma
Intervention  ICMJE
  • Drug: IMCgp100
    soluble gp100-specific T cell receptor with anti-CD3 scFV
  • Drug: durvalumab
    anti-PD-L1 monoclonal antibody
    Other Name: MEDI4736
  • Drug: tremelimumab
    anti-CTLA-4 monoclonal antibody
Study Arms  ICMJE
  • Experimental: Arm 1
    IMCgp100 with durvalumab (MEDI4736)
    • Drug: IMCgp100
    • Drug: durvalumab
  • Experimental: Arm 2
    IMCgp100 with tremelimumab
    • Drug: IMCgp100
    • Drug: tremelimumab
  • Experimental: Arm 3
    IMCgp100 with durvalumab (MEDI4736) and tremelimumab
    • Drug: IMCgp100
    • Drug: durvalumab
    • Drug: tremelimumab
  • Experimental: Arm 4
    IMCgp100 (single agent)
    Intervention: Drug: IMCgp100
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 24, 2020)
Original Estimated Enrollment  ICMJE
 (submitted: August 27, 2015)
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Written informed consent must be obtained from all patients prior to any study procedures
  3. Patients with advanced non-uveal melanoma defined as unresectable stage III or metastatic stage IV disease. Patients with acral or mucosal melanoma are acceptable.
  4. Phase 1b Arm 4 and Phase II: Patients with disease progression following initiation of treatment with an approved PD-1 inhibitor. No prior cytotoxic therapy in the advanced setting is permitted. Patients with BRAF mutations must be refractory to approved BRAF-based therapy. CTLA-4-inhibition therapy is acceptable as a prior line of therapy or in combination with anti-PD-1 therapy.
  5. HLA-A*0201 positive by Central Assay
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  7. Phase II cohorts only: patients must have measurable disease according to RECIST v.1.1 criteria. Patients enrolled in Ph Ib cohorts must have evaluable disease
  8. Ongoing treatment with systemic steroids or other immunosuppressive therapies.

Exclusion Criteria:

  1. Presence of untreated or symptomatic central nervous system metastases, or central nervous system metastases.
  2. History of severe hypersensitivity reactions to other mAbs
  3. History of treatment-related interstitial lung disease/pneumonitis
  4. Impaired baseline organ function as evaluated by out-of-range laboratory values.
  5. Clinically significant cardiac disease or impaired cardiac function.
  6. Active autoimmune disease or a documented history of autoimmune disease.
  7. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy before Screening is initiated
  8. Known history of human immunodeficiency virus (HIV) infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulation
  9. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, currently requiring medical intervention, 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 requiring treatment with currently an unknown status. History of treated hepatitis is not exclusionary
  10. Malignant disease, other than that being treated in this study. Pregnant or breast feeding.
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,   Denmark,   Germany,   Italy,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02535078
Other Study ID Numbers  ICMJE IMCgp100-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Immunocore Ltd
Study Sponsor  ICMJE Immunocore Ltd
Collaborators  ICMJE MedImmune LLC
Investigators  ICMJE
Study Director: Mohammed Dar Immunocore Ltd
PRS Account Immunocore Ltd
Verification Date April 2021

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