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Trial record 3 of 209 for:    Ovarian Dysgenesis 1

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

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ClinicalTrials.gov Identifier: NCT02387125
Recruitment Status : Completed
First Posted : March 12, 2015
Last Update Posted : May 20, 2019
Sponsor:
Information provided by (Responsible Party):
Immune Design

Tracking Information
First Submitted Date  ICMJE March 1, 2015
First Posted Date  ICMJE March 12, 2015
Last Update Posted Date May 20, 2019
Study Start Date  ICMJE February 2015
Actual Primary Completion Date March 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
The nature, frequency and severity of adverse events (AEs) and laboratory abnormalities in subjects receiving CMB305 alone or in combination with oral metronomic CPA or G100 [ Time Frame: Up to 5 years since first study injection ]
To evaluate the safety and tolerability of CMB305 (sequential administered doses of LV305 and G305) alone or in combination with oral metronomic CPA or G100 in subjects with locally advanced, relapsed, or metastatic cancer expressing NY ESO 1
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2015)
Safety and Tolerability by assessing the number of participants experiencing AEs [ Time Frame: Up to 2 years since first study injection ]
To evaluate the safety and tolerability of CMB305 by assessing the number of participants experiencing AEs
Change History Complete list of historical versions of study NCT02387125 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Time to Progression [ Time Frame: Up to 5 years since first study injection ]
    To evaluate clinical responses (by Immune-related Response Criteria (irRC) modified to use RECIST (v 1.1) measurement criteria), time to progression (TTP) and progression-free survival (PFS) as a preliminary assessment of clinical activity
  • Progression Free Survival [ Time Frame: Up to 5 years since first study injection ]
    To evaluate clinical responses (by Immune-related Response Criteria (irRC) modified to use RECIST (v 1.1) measurement criteria), time to progression (TTP) and progression-free survival (PFS) as a preliminary assessment of clinical activity
  • Overall Survival [ Time Frame: Up to 5 years since first study injection ]
    Overall survival (OS), time to progression (TTP), and progression-free survival (PFS) and descriptive tumor responses. Evaluation of response will be by RECIST (v1.1) modified to use irRC measurement criteria and by changes in markers of tumor burden
  • Humoral and cellular immune responses at selected sites, as measured by changes from baseline anti-NY-ESO-1 immunity [ Time Frame: Approximately 14 weeks ]
    To evaluate the cellular and humoral immunogenicity of CMB305 alone or in combination with mCPA or G100 in patients
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2015)
  • Immunogenicity by assessing the frequency of inducing or increasing responses in participants [ Time Frame: Approximately 12 weeks ]
    To evaluate the cellular and humoral immunogenicity of CMB305 by assessing the frequency of inducing or increasing responses in participants
  • Tumor Response: Progression free survival (PFS) [ Time Frame: Up to 2 years since first study injection ]
    Progression free survival (PFS) as defined by immune response related criteria (irRC)
Current Other Pre-specified Outcome Measures
 (submitted: June 30, 2017)
  • To evaluate pre- and post-regimen blood samples for potential biomarkers of immunogenicity and clinical tumor response [ Time Frame: Approximately 14 weeks ]
  • To evaluate available pre- and post-regimen tumor tissue for histologic, immunohistologic, and genomic markers following administration of CMB305 alone or in combination with mCPA or G100 [ Time Frame: Approximately 14 weeks ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1b Safety Study of CMB305 in Patients With Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1
Official Title  ICMJE 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
Brief Summary 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.
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. While this is an exploratory study to evaluate the safety, tolerability and immunogenicity of the CMB305 regimen, the study will also evaluate the safety and response to with oral metronomic CPA or intratumoral G100 in the context of CMB305.

CMB305 is a prime-boost vaccine approach against NY-ESO-1-expressing tumors, designed to generate an integrated, anti-NY-ESO-1 immune response in vivo via a targeted, specific interaction with dendritic cells.

G100 contains a potent synthetic small molecule toll-like receptor-4 (TLR-4) agonist, Glucopyranosyl Lipid A (GLA) that leverages the activation of both innate and adaptive immunity, including dendritic cells, in the tumor microenvironment to create an immune response against the tumor's preexisting diverse set of antigens.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sarcoma
  • Melanoma
  • Non-small Cell Lung Cancer
  • Ovarian Cancer
Intervention  ICMJE
  • Biological: CMB305
  • Biological: G100
  • Drug: Metronomic CPA
    Other Name: Cytoxan Tablets
Study Arms  ICMJE
  • Experimental: Part 1 Dose Escalation of CMB305
    Patients with melanoma, NSCLC, ovarian cancer, or sarcoma will be enrolled. Patients will receive CMB305, a sequential regimen of LV305 and G305. Two cohorts are planned based on LV305 dose.
    Intervention: Biological: CMB305
  • Experimental: Part 2 Expansion of CMB305
    Arm A will enroll up to 9 patients each with NSCLC or ovarian cancer, or up to 18 patients with the sarcoma subtypes, synovial sarcoma or MRCL. Arm B will enroll up to 9 additional patients with selected sarcoma subtypes to explore subcutaneous (SC) dosing of LV305 and G305 on the same schedule. Arm C will enroll up to 9 patients with synovial sarcoma or MRCL for treatment with CMB305 and with oral metronomic CPA. Arm D will enroll up to 9 patients with synovial sarcoma or MRCL at selected sites for treatment with CMB305 and IT G100. Arm E will enroll up to 6 patients with soft tissue sarcoma any subtype for treatment with a higher dose of CMB305 than previous arms.
    Interventions:
    • Biological: CMB305
    • Biological: G100
    • Drug: Metronomic CPA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 26, 2018)
79
Original Estimated Enrollment  ICMJE
 (submitted: March 11, 2015)
33
Actual Study Completion Date  ICMJE March 29, 2019
Actual Primary Completion Date March 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Locally advanced, relapsed, and/or metastatic cancer
  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. At least one tumor must be accessible and patients must consent for biopsies in Arms C and D.
  4. 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. For melanoma: Uveal melanoma or LDH >1.1 x ULN
  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, planning to become pregnant, or nursing
  14. Known allergy(ies) to any component of CMB305 or CPA
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02387125
Other Study ID Numbers  ICMJE IMDZ-C131
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Immune Design
Study Sponsor  ICMJE Immune Design
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Immune Design
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP