Clinical Trials /

Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1

NCT02387125

Description:

This is a Phase 1b, open label, multi-center study of CMB305 (sequentially administered LV305 [a dendritic cell-targeting viral vector expressing the NY-ESO-1 gene] and G305 [NY-ESO-1 recombinant protein plus GLA-SE]) in patients with melanoma, sarcoma, ovarian cancer, or non-small cell lung cancer that express NY-ESO-1.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Sarcoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A <span class="go-doc-concept go-doc-intervention">Phase 1b</span> Safety Study of CMB305 (Sequentially Administered LV305 and G305) in Patients With Locally Advanced, Relapsed, or Metastatic <span class="go-doc-concept go-doc-disease">Cancer</span> Expressing NY-ESO-1

Title

  • Brief Title: A Phase 1b Safety Study of CMB305 (Sequentially Administered LV305 and G305) in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1
  • Official Title: A Phase 1b Study Evaluating the Safety, Tolerability and Immunogenicity of CMB305 (Sequentially Administered LV305 and G305) in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1
  • Clinical Trial IDs

    NCT ID: NCT02387125

    ORG ID: IMDZ-C131

    Trial Conditions

    Sarcoma

    Melanoma

    Non-small Cell Lung Cancer

    Ovarian Cancer

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a Phase 1b, open label, multi-center study of CMB305 (sequentially administered
    LV305 [a dendritic cell-targeting viral vector expressing the NY-ESO-1 gene] and G305
    [NY-ESO-1 recombinant protein plus GLA-SE]) in patients with melanoma, sarcoma, ovarian
    cancer, or non-small cell lung cancer that express NY-ESO-1.

    CMB305 is a novel in vivo approach designed to stimulate the body's immune system to fight
    the spread and growth of cancer for patients whose tumors express the NY-ESO-1 protein.
    LV305 will be given in a prime-boost approach with G305 to induce a synergistic
    immunotherapeutic response.

    Detailed Description

    This study is designed to investigate and examine the safety and immunogenicity of the
    combinatorial regimen called CMB305, where intradermal LV305 is administered sequentially
    with intramuscular G305 over three months. During Part 1, a dose escalation design will be
    utilized in patients with melanoma, NSCLC, ovarian cancer, or sarcoma. After completion of
    Part 1, the study will be expanded in Part 2 and will enroll patients with NSCLC, ovarian
    cancer, synovial sarcoma or myxoid/round cell liposarcoma.

    Trial Arms

    Name Type Description Interventions
    CMB305 Experimental Dose escalation cohorts and Expansion

    Eligibility Criteria

    Inclusion Criteria:

    1. Locally advanced, relapsed, and/or metastatic cancer with low or minimal tumor
    burden, which may or may not be measureable (see Appendix A for descriptions)

    2. Tumor histology consistent with one of the following: In Part 1, Dose Escalation -
    melanoma, NSCLC, ovarian cancer (including fallopian tube carcinoma), or sarcoma (any
    subtype). In Part 2, Patient Expansion - NSCLC, ovarian cancer (including fallopian
    tube carcinoma), or the sarcoma subtypes, synovial sarcoma or myxoid/round cell
    liposarcoma

    3. Tumor specimen positive for NY-ESO-1 expression by IHC and/or RT-PCR

    4. If ovarian cancer, cancer antigen 125 (CA-125) must be 40 U/mL (unless patient has
    measureable disease that cannot be followed by CA-125); if melanoma, LDH must be
    ULN

    5. Inadequate response, relapse, and/or unacceptable toxicity with one or more prior
    systemic, surgical, or radiation cancer therapies, and for whom curative standard
    therapy is not an option (except patients with NSCLC who must have experienced either
    an inadequate response, relapse, and/or unacceptable toxicity with two or more prior
    systemic, surgical, or radiation cancer therapies)

    6. 18 years of age

    7. Life expectancy of 6 months per the investigator

    8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    9. ECG without evidence of clinically significant arrhythmia or ischemia

    10. If female of childbearing potential (FCBP), willing to undergo pregnancy testing and
    agrees to use at least one highly effective or two effective contraceptive methods
    during the dosing period and for three months after last CMB305 injection

    11. If male and sexually active with a FCBP, must agree to use highly effective
    contraception such as latex condom during the dosing period and for three months
    after last CMB305 injection

    Exclusion Criteria:

    1. Investigational therapy within 3 weeks prior to CMB305 dosing

    2. Prior administration of other NY-ESO-1-targeting immunotherapeutics

    3. Significant immunosuppression from:

    1. Concurrent, recent ( 4 weeks ago) or anticipated treatment with systemic
    corticosteroids at any dose, or

    2. Other immunosuppressive medications such as methotrexate, cyclosporine,
    azathioprine (antihistamines, non-steroidal anti-inflammatory drugs and aspirin
    permitted) or conditions such as common variable hypogamma-globulinemia or
    exposures such as large field radiotherapy

    4. Cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors,
    G-CSF or GM-CSF within 3 weeks prior to the first scheduled CMB305 dosing

    5. Psychiatric, other medical illness or other condition that in the opinion of the PI
    prevents compliance with study procedures or ability to provide valid informed
    consent

    6. Significant autoimmune disease with the exception of alopecia, vitiligo,
    hypothyroidism or other conditions that have never been clinically active or were
    transient and have completely resolved and require no ongoing therapy

    7. Myocardial infarction within 6 months of study initiation, active cardiac ischemia or
    New York Heart Association (NYHA) Grade III or IV heart failure

    8. Inadequate organ function including:

    1. Marrow: Peripheral blood leukocyte count (WBC) < 3000/mm3, absolute neutrophil
    count 1500/mm3, platelets < 75000/mm3, or hemoglobin < 10 gm/dL

    2. Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) >
    2.5 x ULN, total serum bilirubin > 1.5 x ULN (patients with Gilbert's Disease
    may be included if their total bilirubin is 3.0 mg/dL)

    3. Renal: Creatinine > 1.5x ULN

    4. Other: INR (prothrombin time ratio) or partial thromboplastin time (PTT) >1.5 x
    ULN

    9. History of other cancer within 3 years (except non-melanoma cutaneous malignancies
    and cervical carcinoma in situ).

    10. Active tuberculosis or recent (< 2 week ago) clinically significant infection or
    evidence of active hepatitis B, hepatitis C or HIV infection

    11. Uveal melanoma

    12. Brain metastases considered unstable as:

    1. Without confirmed stability over 60 days in patients previously treated with
    prior surgery or radiation; OR

    2. Associated with symptoms and/or findings; OR

    3. Requiring corticosteroids or anticonvulsants in the prior 60 days

    13. Pregnant or nursing

    14. Known allergy(ies) to any component of CMB305, including egg lecithin

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 80 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Safety and Tolerability by assessing the number of participants experiencing AEs

    Secondary Outcome Measures

    Immunogenicity by assessing the frequency of inducing or increasing responses in participants

    Tumor Response: Progression free survival (PFS)

    Trial Keywords