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A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors

NCT02650713

Description:

This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab. Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of <span class="go-doc-concept go-doc-intervention">RO6958688</span> in Combination With <span class="go-doc-concept go-doc-intervention">Atezolizumab</span> in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors

Title

  • Brief Title: A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors
  • Official Title: AN OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND EXPANSION PHASE IB STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND THERAPEUTIC ACTIVITY OF RO6958688 IN COMBINATION WITH ATEZOLIZUMAB IN PATIENTS WITH LOCALLY ADVANCED AND/OR METASTATIC CEA-POSITIVE SOLID TUMORS
  • Clinical Trial IDs

    NCT ID: NCT02650713

    ORG ID: WP29945

    NCI ID: 2015-003771-30

    Trial Conditions

    Advanced/Metastatic Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    Atezolizumab RO6958688+Atezolizumab
    RO6958688 RO6958688+Atezolizumab

    Trial Purpose

    This is an open-label, multi-center, dose escalation and expansion Phase IB clinical study
    of RO6958688 in combination with atezolizumab.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    RO6958688+Atezolizumab Experimental Each treatment cycle will be 21 days in duration and will consist of IV infusions of RO6958688 given weekly (QW) (+/- 1 day) in combination with atezolizumab given every 3 weeks (Q3W) (+/- 2 days). Participants will receive atezolizumab (1200 mg fixed dose) IV on Day 1 of each cycle, followed by RO6958688 at least one hour later, given IV on Day 1, Day 8 and Day 15 of each cycle. Atezolizumab, RO6958688

    Eligibility Criteria

    Inclusion Criteria:

    - Confirmed locally advanced and/or metastatic solid tumor in participants who have
    progressed on a standard therapy, are intolerant to standard therapy, and/or are
    non-amenable to standard therapy

    - Life expectancy (in the opinion of the investigator) of >= 12 weeks

    - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1

    - All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical
    procedure must have resolved to Grade <= 1 or returned to baseline, except alopecia
    (any grade) and Grade 2 peripheral neuropathy

    - Adequate hematological, liver, and renal functions

    - Negative serum pregnancy test within 7 days prior to study treatment in premenopausal
    women and women <= 2 years after start of menopause

    - For women of childbearing potential: agreement to remain abstinent (refrain from
    heterosexual intercourse) or use contraceptive methods that result in a failure rate
    of < 1% per year during the treatment period and for at least 90 days after the last
    dose of study drugs

    - Locally confirmed CEA expression in tumor tissue

    Exclusion Criteria:

    - Active or untreated central nervous system (CNS) metastases as determined by computed
    tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and
    prior radiographic assessments

    - Spinal cord compression not definitively treated with surgery and/or radiation or
    previously diagnosed and treated spinal cord compression without evidence that
    disease has been clinically stable for >= 2 weeks prior to enrollment

    - Leptomeningeal disease

    - Malignancies other than non-small-cell lung cancer (NSCLC) within 5 years prior to
    enrollment, with the exception of those with a negligible risk of metastasis or death
    and treated with expected curative outcome (such as adequately treated carcinoma in
    situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer
    treated surgically with curative intent, ductal carcinoma in situ treated surgically
    with curative intent)

    - Significant, uncontrolled concomitant diseases which could affect compliance with the
    protocol or interpretation of results, including diabetes mellitus, pulmonary
    disorders, and known autoimmune diseases

    - Uncontrolled hypertension (systolic blood pressure (BP) > 150 mmHg and/or diastolic
    BP > 100 mmHg), unstable angina, congestive heart failure (CHF) of any New York Heart
    Association (NYHA) classification (Class II or greater), serious cardiac arrhythmia
    requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular
    tachycardia), history of myocardial infarction within 6 months of enrollment

    - Administration of a live, attenuated vaccine within 28 days before Day 1 or
    anticipation that such a live attenuated vaccine will be required during the study

    - Known HIV

    - Active Hepatitis B (HBV) or Hepatitis C (HCV) infection (required at screening)

    - Severe infections within 28 days prior to Day 1, including, but not limited to
    hospitalization for complications of infection, bacteremia, or severe pneumonia or
    active tuberculosis

    - Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1 (Patients
    receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
    infection) are eligible)

    - Any other diseases, metabolic dysfunction, physical examination finding, or clinical
    laboratory finding giving reasonable suspicion of a disease or condition that would
    contraindicate the use of an investigational drug

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Participants with Adverse Events

    Secondary Outcome Measures

    Pharmacokinetic Assessment: Area Under the Concentration Curve (AUC)

    Pharmacokinetic Assessment: Volume of Distribution at Steady State (Vss)

    Pharmacokinetic Assessment: Minimum Serum Concentration (Cmin)

    Pharmacokinetic Assessment: Maximum serum concentration (Cmax)

    Pharmacokinetic Assessment: Time to Cmax (Tmax)

    Pharmacokinetic Assessment: Clearance (CL)

    Pharmacokinetic Assessment: Half-life (t1/2)

    Objective Overall Response Rate (ORR)

    Disease Control Rate (DCR)

    Progression-Free Survival (PFS)

    Overall Survival (OS)

    Trial Keywords