Clinical Trials /

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

NCT03538028

Description:

The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of INCAGN02385 in participants with advanced malignancies.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Diffuse Large B-Cell Lymphoma
  • Endometrial Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Merkel Cell Carcinoma
  • Mesothelioma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies
  • Official Title: A Phase 1 Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN02385 in Participants With Select Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: INCAGN 2385-101
  • NCT ID: NCT03538028

Conditions

  • Cervical Cancer
  • Microsatellite Instability (MSI)-High Endometrial Cancer
  • Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ])
  • Esophageal Cancer
  • Hepatocellular Carcinoma
  • Melanoma (Uveal Melanoma Excluded)
  • Merkel Cell Carcinoma
  • Mesothelioma
  • MSI-high Colorectal Cancer
  • Non-small Cell Lung Cancer (NSCLC)
  • Ovarian Cancer
  • Squamous Cell Carcinoma of the Head and Neck (SCCHN)
  • Small Cell Lung Cancer (SCLC)
  • Renal Cell Carcinoma (RCC)
  • Triple-negative Breast Cancer
  • Urothelial Carcinoma
  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
INCAGN02385INCAGN02385

Purpose

The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of INCAGN02385 in participants with advanced malignancies.

Trial Arms

NameTypeDescriptionInterventions
INCAGN02385ExperimentalPart 1: INCAGN02385 at the protocol-defined starting dose administered every 2 weeks (Q2W), with dose escalation to determine the maximum tolerated dose or pharmacologically active dose. Part 2: INCAGN02385 administered Q2W or Q4W at the recommended dose(s) from Part 1.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Locally advanced or metastatic disease; locally advanced disease must not be amenable
                 to resection with curative intent.
    
              -  Disease progression after treatment with available therapies that are known to confer
                 clinical benefit, or intolerant to treatment, or refuse noncurative standard
                 treatment. There is no limit to the number of prior treatment regimens.
    
              -  Participants with advanced or metastatic cervical cancer, MSI-high endometrial cancer,
                 gastric cancer (including stomach and GEJ), esophageal cancer, hepatocellular
                 carcinoma, melanoma (uveal melanoma excluded), Merkel cell carcinoma, mesothelioma,
                 MSI-high colorectal cancer, NSCLC, ovarian cancer, SCCHN, SCLC, RCC, triple-negative
                 breast cancer, and urothelial carcinoma, or alternative immunogenic tumor types with
                 medical monitor approval. Participants with DLBCL may participate in Part 2 of the
                 study.
    
              -  Presence of measureable disease based on RECIST v1.1 for solid tumors or the Lugano
                 classification for DLBCL.
    
              -  Willingness and ability to safely undergo pretreatment and on-treatment tumor
                 biopsies.
    
              -  Eastern Cooperative Oncology Group performance status 0 or 1.
    
            Exclusion Criteria:
    
              -  Laboratory and medical history parameters outside the protocol-defined range.
    
              -  Transfusion of blood products (including platelets or red blood cells) or
                 administration of colony-stimulating factors (including granulocyte colony-stimulating
                 factor, granulocyte macrophage colony-stimulating factor, or recombinant
                 erythropoietin) within 14 days before study Day 1.
    
              -  Receipt of anticancer medications or investigational drugs within protocol-defined
                 intervals before the first administration of study drug.
    
              -  Receipt of a live vaccine within 30 days of planned start of study drug.
    
              -  Active autoimmune disease that required systemic treatment in the past.
    
              -  Known active CNS metastases and/or carcinomatous meningitis.
    
              -  Known additional malignancy that is progressing or requires active treatment, or
                 history of other malignancy within 2 years of study entry. See protocol-defined
                 exceptions.
    
              -  Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
    
              -  Active infection requiring systemic therapy.
    
              -  Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
    
              -  Known history of HIV (HIV 1/2 antibodies).
    
              -  Prior treatment with an anti-LAG-3 antibody for any indication.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of treatment-emergent adverse events (TEAEs)
    Time Frame:Up to 12 months
    Safety Issue:
    Description:TEAE defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.

    Secondary Outcome Measures

    Measure:Cmax of INCAGN02385
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Maximum observed plasma concentration.
    Measure:Tmax of INCAGN02385
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Time to maximum plasma concentration.
    Measure:Cmin of INCAGN02385
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Minimum observed plasma concentration during the dosing interval.
    Measure:AUC0-t of INCAGN02385
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.
    Measure:Objective response rate (ORR) in participants with advanced or metastatic solid tumors
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Defined as the percentage of participants having complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
    Measure:Disease control rate (DCR) in participants with advanced or metastatic solid tumors
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Defined as percentage of participants having CR, PR, or stable disease (SD) as best on-study response.
    Measure:Duration of response (DOR) in participants with advanced or metastatic solid tumors
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression per RECIST v1.1 or death from any cause, if occurring sooner than progression.
    Measure:Progression-free survival (PFS) in participants with advanced or metastatic solid tumors
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Defined as the time from date of first dose of study drug until the earliest date of disease progression per RECIST v1.1 or death from any cause if occurring sooner than progression.
    Measure:ORR in participants with diffuse large B-cell lymphoma (DLBCL)
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Defined as the percentage of participants with a CR/complete metabolic response (CMR) or PR/partial metabolic response (PMR) per the Lugano Classification.
    Measure:DOR in participants with DLBCL
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression per radiographic disease assessment or death from any cause among participants who achieve an objective response.
    Measure:PFS in participants with DLBCL
    Time Frame:Up to 12 months
    Safety Issue:
    Description:Defined as the time from the date of the first dose of study drug until the earliest date of disease progression per radiographic disease assessment or death from any cause if occurring sooner than progression.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Incyte Biosciences International Sàrl

    Trial Keywords

    • lymphocyte activation gene (LAG)
    • LAG-3
    • advanced solid tumor
    • metastatic solid tumor
    • relapsed/refractory DLCBL

    Last Updated