Clinical Trials /

First-in-human Study With the Antibody-drug Conjugate SYD985 to Evaluate Safety and Efficacy in Cancer Patients

NCT02277717

Description:

The purpose of this study is to evaluate the safety of a new medicinal drug SYD985 at different dose levels in patients with cancer, to understand how SYD985 is handled by the body and to evaluate the effect of SYD985 on the cancer.

Related Conditions:
  • Breast Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

First-in-human Study With the <span class="go-doc-concept go-doc-intervention">Antibody-drug Conjugate</span> SYD985 to Evaluate Safety and Efficacy in <span class="go-doc-concept go-doc-disease">Cancer</span> Patients

Title

  • Brief Title: First-in-human Study With the Antibody-drug Conjugate SYD985 to Evaluate Safety and Efficacy in Cancer Patients
  • Official Title: A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT02277717

    ORG ID: SYD985.001

    Trial Conditions

    Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    SYD985 (trastuzumab vc-seco-DUBA) SYD985 (trastuzumab vc-seco-DUBA)

    Trial Purpose

    The purpose of this study is to evaluate the safety of a new medicinal drug SYD985 at
    different dose levels in patients with cancer, to understand how SYD985 is handled by the
    body and to evaluate the effect of SYD985 on the cancer.

    Detailed Description

    Cancer cells can have different kinds of proteins on their cell surface; one of these is the
    protein HER2. HER2 plays an important role in the development of cancer. High expression of
    HER2 is related to poor prognosis. Although several cancer drugs are available that work via
    the HER2 protein, a substantial portion of these patients still does not benefit from these
    treatments.

    The new cancer drug SYD985 is being developed by Synthon Biopharmaceuticals BV. SYD985 is an
    antibody-drug conjugate and consists of two parts: an antibody and a linker-drug moiety
    containing a toxin. The antibody part binds to HER2 on the surface of the cancer cell. When
    SYD985 binds to this cancer cell, it will be internalized by the cell. After proteolytic
    cleavage of the linker, the toxin will be split off in the cell and the cancer cell will be
    killed. Thus, SYD985 can be considered as a form of targeted chemotherapy.

    This is the first study in which SYD985 is administered to humans. The study consists of two
    parts:

    Part I is the dose-escalation part in which a low dose of SYD985 is given to three cancer
    patients. If it is well tolerated, a higher dose of SYD985 will be given to 3 other cancer
    patients. This will continue until a further dose increase is not safe anymore.

    In Part II of the study, several groups of patients with a specific type of cancer will
    receive the SYD985 dose which has been selected for further evaluation.

    All patients from both parts of the study will receive SYD985 infusions every three weeks
    until progression of the cancer or unacceptable toxicity develops.

    Trial Arms

    Name Type Description Interventions
    SYD985 (trastuzumab vc-seco-DUBA) Experimental SYD985 (trastuzumab vc-seco-DUBA)

    Eligibility Criteria

    Main Inclusion Criteria:

    1. Patient with histologically-confirmed, locally advanced or metastatic tumor who has
    progressed on standard therapy or for whom no standard therapy exists, with the
    following restriction:

    - Part I: solid tumors of any origin;

    - Part II: breast and gastric tumors;

    2. For Part II: HER2 tumor status as defined in the protocol;

    3. ECOG performance status 1;

    4. Life expectancy > 12 weeks;

    5. Adequate organ function;

    6. For Part II: measurable disease.

    Main Exclusion Criteria:

    1. Anthracycline treatment within 3 months and/or abnormal cardiac biomarker values;

    2. Other anticancer therapy (except for LHRH agonists) within 4 weeks (6 weeks for
    trastuzumab, (ado-)trastuzumab emtansine, nitrosoureas and mitomycin C);

    3. History of infusion-related reactions and/or hypersensitivity to trastuzumab or
    (ado-) trastuzumab emtansine;

    4. Severe, uncontrolled systemic disease;

    5. LVEF < 55%, or a history of absolute decrease in LVEF of 10% points to < 50% during
    previous treatment with trastuzumab or (ado-)trastuzumab emtansine, or a history of
    decrease in LVEF to < 40% during previous treatment with trastuzumab or
    (ado-)trastuzumab emtansine;

    6. History of clinically significant CV disease;

    7. Symptomatic brain metastasis, or therapy for brain metastasis (excluding PCI and
    dexamethasone treatment with stable or decreasing daily dose) within 4 weeks.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of dose-limiting toxicities

    Secondary Outcome Measures

    Number of patients with adverse events

    Area under the plasma concentration versus time curve (AUC) of SYD985

    Peak plasma concentration of SYD985

    Change from baseline in hematology and blood chemistry parameters

    Number of patients with antibodies against SYD985

    Objective response rate

    Trial Keywords

    cancer

    metastasis

    HER2

    trastuzumab

    duocarmycin

    SYD985

    antibody-drug conjugate

    ADC

    trastuzumab vc-seco-DUBA