Clinical Trials /

Phase 1, Multiple Ascending Dose Study of Anti-HER2 FCAB FS102 in HER2 Positive Solid Tumors (Anti HER2 Fcab)

NCT02286219

Description:

To evaluate the safety, tolerability, dose limiting toxicity (DLT), and maximum tolerated dose (MTD), of FS102(BMS-986186) when administered intravenously (IV) to subjects with relapsed or refractory solid tumors that overexpress HER2 and who have no standard treatment options.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Phase 1, Multiple Ascending Dose Study of Anti-<span class="go-doc-concept go-doc-biomarker">HER2</span> FCAB <span class="go-doc-concept go-doc-intervention">FS102</span> in <span class="go-doc-concept go-doc-biomarker">HER2</span> Positive Solid Tumors (Anti <span class="go-doc-concept go-doc-biomarker">HER2</span> Fcab)

Title

  • Brief Title: Phase 1, Multiple Ascending Dose Study of Anti-HER2 FCAB FS102 in HER2 Positive Solid Tumors (Anti HER2 Fcab)
  • Official Title: Phase 1, Multiple Ascending Dose Study of Anti-HER2 FCAB FS102 in HER2 Positive Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02286219

    ORG ID: CA014-001

    NCI ID: FS10214100

    Trial Conditions

    Solid Tumors That Overexpress HER2 (HER2 Positive)

    Trial Interventions

    Drug Synonyms Arms
    FS102 Fcab, Fc region of full immunoglobulin G, subclass 1 [IgG1] FS102

    Trial Purpose

    To evaluate the safety, tolerability, dose limiting toxicity (DLT), and maximum tolerated
    dose (MTD), of FS102(BMS-986186) when administered intravenously (IV) to subjects with
    relapsed or refractory solid tumors that overexpress HER2 and who have no standard treatment
    options.

    Detailed Description

    This is a Phase 1, open-label, multiple dose escalation study in subjects with solid tumors
    that over express HER2.

    Subjects with locally un-resectable and/or metastatic solid cancers that over express human
    epidermal growth factor tyrosine kinase receptor 2 (HER2) by standard clinical pathology
    criteria and who have no standard treatment options will be enrolled into a series of
    escalating dose cohorts.

    Within each dose cohort, subjects will receive weekly ( 1 day) or less frequent (i.e Q3W or
    Q2W) IV infusions of FS102 during an initial 28-day (4-week) DLT observation period. During
    the DLT observation period, subjects will be assessed for safety, tolerability, dose
    limiting toxicity, PK, immunogenicity, and clinical disease response. Following assessment
    by the Investigator, subjects without clinical disease progression and without unacceptable
    toxicity will be eligible to continue receiving FS102 for up to six 21 (Q3W) to 28-day
    (weekly or Q2W) cycles.

    Continuation Phase. Subjects who complete six 21-28-day cycles of treatment will be
    evaluated for entry into an extended Continuation Phase of the study. Subjects will be
    eligible for continuation if:

    - They demonstrate no evidence of disease progression;

    - In the opinion of the Investigator they are deemed reasonably likely to continue to
    benefit from treatment; and

    - They have not experienced any toxicity requiring discontinuation. During the
    Continuation Phase, subjects will continue to receive FS102 at the same dose they were
    originally assigned, unless modified downward for earlier toxicity. No dose escalation
    within subjects will be permitted.

    Treatment may continue until one of the following criteria applies:

    - Disease progression;

    - Intervening illness that prevents further administration of treatment;

    - Unacceptable adverse events;

    - Significant subject non-compliance with protocol;

    - Pregnancy;

    - Subject decides to withdraw from study;

    - General or specific changes in the subject's condition that render the subject
    unacceptable for further treatment in the judgment of the Investigator; or

    - Sponsor decides to end the study.

    Trial Arms

    Name Type Description Interventions
    FS102 Experimental Dose escalation of either weekly, Q3W or Q2W doses of FS102 FS102

    Eligibility Criteria

    For more information regarding BMS clinical trial participation, please visit
    www.BMSStudyConnect.com

    Inclusion Criteria:

    1. Signed written informed consent obtained prior to performing any study procedure,
    including screening procedures.

    2. Men and women 18-years-old on the day of signing informed consent.

    3. Subjects must have histologically or cytologically confirmed solid tumor malignancy
    that is unresectable/locally advanced and/or metastatic and for which standard
    curative or palliative measures are not available or are no longer effective (for all
    subjects, histologic or cytologic proof of malignancy based on prior primary cancer
    pathology is acceptable).

    4. Subjects must have HER2-positive tumors and written clinical pathology report
    documentation of HER2 status available for Sponsor's Medical Monitor review.

    1. Assessment of HER2 status in subjects with breast cancer should follow the 2013
    American Society of Clinical Oncology (ASCO)/College of American Pathologists
    (CAP) criteria (Wolff et al, 2013) as practicable.

    2. Assessment of HER2 status in subjects with gastric and gastroesophageal junction
    adenocarcinoma should follow the criteria published by Rschoff et al (2012) as
    practicable.

    3. Assessment of HER2 status in subjects with non-breast/non-gastric cancers may
    follow local institutional criteria. These criteria should be made available to
    the Sponsor.

    4. All subjects with breast and gastric/gastroesophageal junction cancers should
    have HER2 testing performed using an assay kit/methodology specifically
    FDA-approved for their cancer type as practicable.

    5. Subjects for whom the clinical pathology report includes only IHC as 3+ (does
    not reflex to ISH) may enroll without a written report of ISH determined HER2
    copy number, provided the investigative site confirms that archival tissue is
    available.

    5. Subjects with breast cancer must have been treated with at least two FDA-approved
    anti-HER2 directed therapies (more than two is also permissible), and subjects with
    gastric and gastroesophageal junction cancers must have been treated with at least
    one FDA-approved anti-HER2 directed therapy (more than one is also permissible); and
    all subjects must have refractory or relapsed/progressive disease during or following
    their last prior anti-HER2 directed therapy.

    1. Subjects enrolling in the study who have non-breast, non-gastric,
    non-gastroesophageal junction cancers do not require any prior treatment with
    anti-HER2 therapy if there is no FDA-approved anti-HER2 agent for their specific
    cancer type, but they must have refractory or relapsed/progressive disease
    during or following their last prior anti-cancer therapy.

    2. For all subjects, prior post-operative adjuvant administration of anti-HER2
    therapy is permissible.

    6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 and estimated
    life expectancy 3 months.

    7. Any prior cumulative doxorubicin dose must be 360 mg/m2; prior cumulative
    epirubicin dose must be 720 mg/m2.

    8. Adequate organ function as defined below:

    1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2.5
    upper limit of normal (ULN); if liver function abnormalities are due to the
    underlying malignancy, then AST and ALT must be 5 ULN;

    2. Total serum bilirubin ULN unless due to Gilbert's Syndrome;

    3. Serum creatinine 1.25 x ULN; or if serum creatinine > 1.25 ULN, then
    calculated (Cockcroft-Gault formula, glomerular filtration rate (GFR) 60
    mL/min;

    4. Hemoglobin 9.0 g/dL and not requiring > 1 unit red blood cell transfusion per
    month; subjects receiving therapeutic erythropoietin preparations in accordance
    with the FDA product label are eligible to enroll;

    5. Absolute neutrophil count 1,500/mm3 (not supported by growth factors in the
    preceding 21 days);

    6. Platelet count 100,000/mm3 (without platelet transfusion or growth factor
    support in the preceding 7 days);

    7. Activated partial thromboplastin time (aPTT) 1.25 ULN and international
    normalized ratio (INR) 1.3 (unless the subject is receiving therapeutic
    anticoagulants);

    8. Left ventricular ejection fraction (LVEF) determined by 2 dimensional
    echocardiogram (2D Echo) or multi-gated acquisition scan (MUGA) 50% or local
    institutional lower limit normal (LLN) whichever is higher.

    9. Serum magnesium, calcium, and phosphorus must be within normal reference ranges
    as per local tests. [If initial screening results are outside of normal
    reference range, the Investigator may initiate appropriate measures to correct.
    However administration of FS102 may not proceed until the specified electrolytes
    have normalized.]

    9. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
    test (minimum sensitivity 25 IU/L or equivalent units of HCG) during screening for
    eligibility assessments and enrollment and within 24 hours prior to the start of
    study drug.

    10. Women must not be breastfeeding

    11. WOCBP must agree to follow instructions for method(s) of contraception for the
    duration of treatment with study drug FS102 plus 30 days (duration of ovulatory
    cycle) for a total of 30 days post-treatment completion.

    12. Males who are sexually active with WOCBP must agree to follow instructions for
    method(s) of contraception for the duration of treatment with study drug FS102 plus
    90 days (duration of sperm turnover) for a total of 90 days post-treatment
    completion.

    13. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt
    from contraceptive requirements. However they must still undergo pregnancy testing
    as described in this section.

    Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on
    the importance of pregnancy prevention and the implications of an unexpected pregnancy.
    Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on
    the use of highly effective methods of contraception. Highly effective methods of
    contraception have a failure rate of < 1% when used consistently and correctly.

    At a minimum, subjects must agree to the use of two methods of contraception, with one
    method being highly effective and the other method being either highly effective or less
    effective as listed below.

    Exclusion Criteria:

    1. Primary brain or other central nervous system malignancy.

    2. Any history of leptomeningeal metastasis.

    3. Active brain metastasis or treatment for brain metastasis within 1 month of scheduled
    dosing day 1.

    a. Dose of corticosteroid, if any, for brain metastasis must be tolerated in terms of
    glucose tolerance Grade 2 (symptomatic; dietary modification or oral agent
    indicated) and hyperglycemia Grade 2 (fasting glucose value >160 - 250 mg/dL [> 8.9
    - 13.9 mmol/L]).

    4. History of second or other primary cancer with the exception of: 1) curatively
    treated non-melanomatous skin cancer; 2) curatively treated cervical or breast
    carcinoma in situ; or 3) other primary solid tumor treated with curative intent and
    no known active disease present and no treatment administered during the last 3
    years.

    5. Receipt of any investigational treatment within 4 weeks of scheduled dosing day 1.

    6. Receipt of cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and
    mitomycin C) of scheduled dosing day 1.

    7. Receipt of radiation therapy within 3 weeks of scheduled dosing day 1, unless the
    radiation comprised a limited field to non-visceral structures (eg, a limb bone
    metastasis).

    8. Receipt of treatment with immunotherapy (including interferons, interleukins,
    immunoconjugates), biological therapies (including monoclonal antibodies or other
    engineered proteins), targeted small molecules (including but not limited to kinase
    inhibitors), hormonal therapies (except for gonadotropin releasing hormone
    agonists/antagonists for prostate cancer which may be continued while on study)
    within 3 weeks of scheduled dosing day 1.

    9. Receipt of trastuzumab, pertuzumab, or ado-trastuzumab emtansine within 4 weeks of
    scheduled dosing day 1.

    10. Receipt of lapatinib within 7 days of scheduled dosing day 1.

    11. Is concurrently enrolled in another therapeutic clinical trial involving ongoing
    therapy with any investigational or marketed product or placebo.

    12. Exclusionary concurrent medical conditions:

    1. Hypertension which is not controlled to systolic < 160 mm Hg and diastolic < 90
    mm Hg;

    2. Myocardial infarction, unstable angina, coronary artery bypass graft, coronary
    artery angioplasty or stent placement within 12 months before scheduled dosing
    day 1;

    3. History of congestive heart failure;

    4. History of absolute decrease in LVEF of 16 absolute percentage points, or 10
    absolute percentage points and crossing from > LLN to < LLN on prior anti-HER2
    therapy, even if asymptomatic and the LVEF decrease recovered;

    5. Abnormal 12-lead electrocardiogram (ECG) judged to be clinically significant by
    the Investigator;

    6. Hemorrhagic, embolic, or thrombotic stroke within 6 months of scheduled dosing
    day 1;

    7. Prior bone marrow or stem cell transplant;

    8. Previously known infection with human immunodeficiency virus (HIV); or,
    hepatitis B or C requiring treatment;

    9. Any active infection requiring the use of parenteral anti-microbial agents or
    that is > Grade 2;

    10. Non-malignant interstitial lung disease;

    11. Dyspnea of any cause requiring supplemental oxygen therapy;

    12. Significant traumatic injury or major surgery (major surgery means opening of a
    body cavity, eg, thoracotomy, laparotomy, laparoscopic organ resection, and
    major orthopedic procedures, eg, joint replacement, open reduction and internal
    fixation) within 21 days of scheduled dosing day 1;

    13. Any other acute or chronic medical or psychiatric condition (including alcohol
    and illicit substance abuse) or laboratory abnormality that could increase the
    risk associated with study participation or could interfere with the
    interpretation of the study results and, in the judgment of the Investigator or
    Medical Monitor, would render the subject inappropriate for participation in the
    study.

    13. Has not recovered from the adverse effects of previous anti-cancer treatments to
    pre-treatment baseline or Grade 1, except for alopecia, anemia (hemoglobin must meet
    the present study inclusion criterion), and peripheral neuropathy (which must have
    recovered to Grade 2).

    14. Hypersensitivity/infusion reaction to monoclonal antibodies, other therapeutic
    proteins, or allergy to any component/excipient of FS102 finished drug product
    (arginine, glycine, phosphoric acid, or polysorbate 80) and the reaction could not be
    controlled or prevented on subsequent infusion with standard therapies such as
    anti-histamines, 5-HT3 antagonists, or corticosteroids.

    15. Subjects who are pregnant or breast feeding.

    16. Subjects who are unable or unwilling to comply with all study requirements for
    clinical visits, examinations, tests, and procedures.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Adverse events as assessed by NCI Common Toxicity Criteria for Adverse Events CTCAE v3.0

    Secondary Outcome Measures

    Clinical benefit as assessed by objective response rate

    PK profile as assessed by drug levels

    Adverse events as assessed by immune response to drug

    Trial Keywords