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A Study of Emactuzumab and RO7009789 Administered in Combination in Participants With Advanced Solid Tumors

NCT02760797

Description:

This is an open-label, multicenter study designed to assess the safety, pharmacokinetics, pharmacodynamics, and therapeutic activity of emactuzumab and RO7009789 administered in combination in participants with locally advanced or metastatic solid tumors that are not amenable to standard treatment. This study will be conducted in two parts: a dose-finding stage (Part I) and an expansion stage (Part II).

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Melanoma
  • Mesothelioma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A Study of Emactuzumab and RO7009789 Administered in Combination in Participants With Advanced Solid Tumors

Title

  • Brief Title: A Study of Emactuzumab and RO7009789 Administered in Combination in Participants With Advanced Solid Tumors
  • Official Title: AN OPEN-LABEL, MULTICENTER, DOSE-ESCALATION PHASE IB STUDY WITH EXPANSION PHASE TO INVESTIGATE THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS AND THERAPEUTIC ACTIVITY OF EMACTUZUMAB AND RO7009789 ADMINISTERED IN COMBINATION IN PATIENTS WITH ADVANCED SOLID TUMORS
  • Clinical Trial IDs

    NCT ID: NCT02760797

    ORG ID: BP29427

    NCI ID: 2015-004348-21

    Trial Conditions

    Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    Emactuzumab RO5509554 Part 1 (Dose Escalation): Emactuzumab + RO7009789, Part 2 (Dose Expansion): Emactuzumab + RO7009789
    RO7009789 Part 1 (Dose Escalation): Emactuzumab + RO7009789, Part 2 (Dose Expansion): Emactuzumab + RO7009789

    Trial Purpose

    This is an open-label, multicenter study designed to assess the safety, pharmacokinetics,
    pharmacodynamics and therapeutic activity of emactuzumab and RO7009789 administered in
    combination in participants with advanced solid tumors. This study will be conducted in two
    parts: dose escalation stage (Part 1) and an expansion stage (Part 2).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Part 1 (Dose Escalation): Emactuzumab + RO7009789 Experimental Emactuzumab and RO7009789 will be administered intravenously (IV) at a starting dose of 500 milligrams (mg) for emactuzumab and 2 mg for RO7009789. Treatments will continue maximum up to 2 years. Emactuzumab, RO7009789
    Part 2 (Dose Expansion): Emactuzumab + RO7009789 Experimental Emactuzumab and RO7009789 will be administered IV at the maximum tolerated dose defined in Part 1 of the study. Treatments will continue maximum up to 2 years. Emactuzumab, RO7009789

    Eligibility Criteria

    Inclusion Criteria:

    - Eastern Cooperative Oncology Group performance status 0 or 1

    - Participants must have histologically confirmed diagnosis of locally advanced and/or
    metastatic triple negative breast cancer, ovarian cancer, gastric cancer, colorectal
    cancer, pancreatic cancer, melanoma or mesothelioma

    - Radiologically measurable and clinically evaluable disease as per RECIST version 1.1

    - Life expectancy of greater than or equal to (>=) 16 weeks

    - Ability to comply with the collection of tumor biopsies; tumors must be accessible
    for biopsy

    - Adequate bone marrow, liver, cardiac, and renal function

    Exclusion Criteria:

    - Allergy or hypersensitivity to components of either study drug formulation

    - Active or untreated central nervous system (CNS) metastases as determined by computed
    tomography (CT) or magnetic resonance imaging evaluation during screening or prior
    radiographic assessments. Participants with radiographically stable, asymptomatic
    previously irradiated lesions are eligible provided Participant is >= 4 weeks beyond
    completion of cranial irradiation and >/= 3 weeks off of corticosteroid therapy

    - Participants with leptomeningeal disease, Participants with metastases to the brain
    stem, midbrain, pons, medulla, or within 10 millimeters (mm) of the optic apparatus
    (optic nerves and chiasm) are excluded

    - History of Human Immunodeficiency Virus (HIV)

    - Participants with active hepatitis B, active hepatitis C, or active tuberculosis

    - Pregnant or lactating women

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Percentage of Participants With Dose-limiting Toxicities (DLTs)

    Secondary Outcome Measures

    Percentage of Participants With Anti-drug Antibodies (ADA) to Emactuzumab

    Percentage of Participants With ADA to RO7009789

    Maximum Serum Concentration (Cmax) of Emactuzumab

    Serum Concentration of Emactuzumab at the Beginning of Cycle 2 and at the Beginning of Every Subsequent Cycle (Ctrough)

    Area Under the Concentration-time Curve (AUC) of Emactuzumab

    Total Clearance (CL) of Emactuzumab

    Volume of Distribution at Steady-state (Vss) of Emactuzumab

    Accumulation Ratio of Emactuzumab

    Terminal Elimination Half-life (t1/2) of Emactuzumab

    Concentration of Emactuzumab at the Time of Tumor Progression (Cprog)

    Concentration of Emactuzumab at the time of Tumor Response (Complete Response/Partial Response)

    Concentration of Emactuzumab at the Time of Infusion-related Reaction (IRR) or Hypersensitivity Reaction

    Cmax of RO7009789

    Ctrough of RO7009789

    AUC of RO7009789

    CL of RO7009789

    Vss of RO7009789

    Accumulation Ratio of RO7009789

    t1/2 of RO7009789

    Total Tumor-associated Macrophages (TAMs) in Paired-tumor Biopsies

    Total Dermal Macrophages in Paired-skin Biopsies

    Levels of Functional Tumor-infiltrating Lymphocytes

    Circulating Colony-stimulating Factor 1 (CSF-1) Serum Levels

    Total Monocytes Count in Peripheral Blood

    Total Dendritic Cells Count in Peripheral Blood

    Circulating Cluster of Differentiation 4 (CD4) Negative T-Cells Count in Peripheral Blood

    Circulating CD8 Negative T-Cells Count in Peripheral Blood

    Circulating B Cells Count in Peripheral Blood

    Metabolic Response of Target Lesions Assessed as the Change in Standardized Uptake Values (SUV) Max on [18F]-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)

    Percentage of Participants With Best Overall Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and Modified RECIST

    Percentage of Participants With Overall Response as Assessed by RECIST v1.1 and Modified RECIST

    Progressive-free Survival (PFS) as Assessed by RECIST v1.1 and Modified RECIST

    Duration of Response (DOR) as Assessed by RECIST v1.1 and Modified RECIST

    Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1 and Modified RECIST

    Trial Keywords