Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 1b DV281 With an Anti-PD-1 Inhibitor in NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03326752
Recruitment Status : Active, not recruiting
First Posted : October 31, 2017
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
Dynavax Technologies Corporation

Tracking Information
First Submitted Date  ICMJE October 19, 2017
First Posted Date  ICMJE October 31, 2017
Last Update Posted Date June 11, 2019
Actual Study Start Date  ICMJE September 20, 2017
Estimated Primary Completion Date August 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2018)
  • Dose Escalation [ Time Frame: DLT assessment period - Day 1 through Day 28. ]
    Incidence of dose-limiting toxicities (DLTs)
  • Dose Expansion [ Time Frame: 1 year after last subject is enrolled in the Dose Expansion phase of study ]
    Objective response rate (ORR) of dosing regimen established during the Dose Escalation
  • Dose Expansion [ Time Frame: 1 year after last subject is enrolled in the Dose Expansion phase of the Study ]
    Duration of Response (DOR) and time to response.
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2017)
  • Dose Escalation [ Time Frame: DLT assessment period - Day 1 through Day 28. ]
    Incidence of dose-limiting toxicities (DLTs)
  • Dose Expansion [ Time Frame: 1 year after last subject is enrolled in the Dose Expansion phase of study ]
    Dosing regimen established during the Dose Escalation phase of the study based on safety and pharmacodynamics
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • Dose Escalation [ Time Frame: IFN response assessment period - Day 1 through Day 21 ]
    Assess IFN-a induced gene expression in blood when DV281 is administered as a monotherapy and in combination with an approved anti-PD-1 inhibitor
  • Dose Expansion [ Time Frame: 1 year after last subject is enrolled in the Dose Expansion phase of study ]
    Incidence of treatment related AE's as assessed by CTCAE Version 4.03
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2017)
  • Dose Escalation [ Time Frame: IFN response assessment period - Day 1 through Day 21 ]
    Access IFN-a induced gene expression in blood when DV281 is administered as a monotherapy and in combination with an approved anti-PD-1 inhibitor
  • Dose Expansion [ Time Frame: 1 year after last subject is enrolled in the Dose Expansion phase of study ]
    Incidence of treatment related AE's as assessed by CTCAE Version 4.03
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1b DV281 With an Anti-PD-1 Inhibitor in NSCLC
Official Title  ICMJE Phase 1b Dose Escalation and Dose Expansion Trial of DV281 in Combination With an Approved Anti-PD-1 Inhibitor in Subjects With Advanced Non-Small Cell Lung Cancer
Brief Summary This open-label, multicenter, dose-escalation and expansion trial is designed to evaluate the safety and preliminary efficacy of inhaled DV281 in combination with nivolumabfor the treatment of NSCLC and to select a recommended phase 2 dose (RP2D).
Detailed Description Pre-clinical studies support the proposed dosing schema to be tested and a potential benefit of the combination of inhaled DV281 with nivolumab for subjects with advanced NSCLC. This study (DV9-NSC-01) is designed for establishing an immunologically optimal RP2D for inhaled DV281 in combination with an approved anti-PD-1 inhibitor. This trial, studying the potential to enhance the efficacy of an approved anti-PD-1 inhibitor in subjects with advanced NSCLC, addresses an unmet need for NSCLC patients having tumors that do not respond or do not respond adequately to anti-PD-1 inhibitor monotherapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
  • In the Dose Escalation phase of the study, 5 DV281 dose cohorts will be evaluated in combination with an approved anti-PD-1 Inhibitor.
  • The Dose Expansion phase of the study will establish the Recommended Phase 2 Dose of DV281 in combination with an approved anti-PD-1 inhibitor.
Masking: None (Open Label)
Masking Description:
N/A - There is no masking in this study.
Primary Purpose: Treatment
Condition  ICMJE Advanced Non Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: DV281
    - Dose Escalation will be the preliminary dose finding phase of the study. Subjects will be enrolled to available Dosing Cohorts.
  • Device: Breath Actuated Nebulizer
    Breath-actuated, electronic system designed to aerosolize liquid medication.
    Other Name: Nebulizer
  • Drug: DV281 (RP2D)
    - Dose Expansion will be enrolled into 4 groups based on NSCLC characteristics.
  • Drug: Approved Anti-PD-1 Inhibitor
    FDA approved Anti-PD-1 Inhibitor
    Other Name: nivolumab
Study Arms  ICMJE
  • Experimental: Dose Escalation Cohort 1-5

    Cohort 1-4

    • DV281 - Dose Level 1-5
    • DV281 in combination with nivolumab
    • DV281 is administered via a breath actuated nebulizer
    Interventions:
    • Drug: DV281
    • Device: Breath Actuated Nebulizer
    • Drug: Approved Anti-PD-1 Inhibitor
  • Experimental: Dose Expansion (RP2D)

    4 Cohorts

    • Preliminary Recommended Phase 2 dosing of DV281 in combination with nivolumab
    • Cohort 1: Non-squamous and non-EGFR/ ALK mutation and progressed on anti-PD-1/L1 therapy
    • Cohort 2: Non-squamous and EGFR/ ALK mutation and progressed on targeted therapy
    • Cohort 3: Squamous and anti-PD-1/ L1 therapy experienced
    • Cohort 4: Squamous and anti-PD-1/L1 therapy naive
    • DV281 is administered via a breath actuated nebulizer.
    Interventions:
    • Device: Breath Actuated Nebulizer
    • Drug: DV281 (RP2D)
    • Drug: Approved Anti-PD-1 Inhibitor
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 10, 2019)
26
Original Estimated Enrollment  ICMJE
 (submitted: October 25, 2017)
80
Estimated Study Completion Date  ICMJE August 30, 2020
Estimated Primary Completion Date August 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have documented histologically or cytologically confirmed advanced NSCLC as the dominant histology.
  • If confirmed EGFR or ALK directed testing warrants actionable targeted therapy, must have confirmed disease progression on targeted therapy or cannot tolerate targeted therapy.
  • Aged 18 years and older on the day of signing informed consent
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 for Dose Escalation phase and ECOG PS 0 to 1 for Dose Expansion phase
  • Adequate organ function as indicated by laboratory values
  • Life expectancy, in the opinion of the investigator, of at least 3 months

Exclusion Criteria

  • Condition of the subjects lung anatomy is such that proper delivery of inhaled DV281 to the specific location of intra-thoracic tumor(s) could be compromised
  • Any known additional malignancy that is progressing or required active treatment in the last 3 years
  • Current or history of clinically significant non-infectious pneumonitis
  • History of clinically severe lung disease, asthma, or chronic obstructive pulmonary disease (COPD) requiring emergency management and/or hospitalization in the last year
  • Received more than 30 Gy of conventional radiation therapy in the thoracic region within 26 weeks prior to study enrollment
  • Is expected to require any other form of anti-cancer therapy while in the trial. Zoledronic acid or denosumab as supportive care for bone metastases will be allowed if started prior to study enrollment
  • Diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10 mg of prednisone or equivalent) or any other form of immunosuppressive therapy (including immune modulators or systemic corticosteroids) that cannot be discontinued safely within 14 days prior to study enrollment
  • Has a medical condition that requires immunosuppression
  • Active autoimmune disease requiring systemic treatment in the past 2 years or a disease that requires immunosuppressive medication including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Known central nervous system metastases, brain metastases, or carcinomatous meningitis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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 NCT03326752
Other Study ID Numbers  ICMJE DV9-NSC-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dynavax Technologies Corporation
Study Sponsor  ICMJE Dynavax Technologies Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Edward Garon, MD University of California, Los Angeles
PRS Account Dynavax Technologies Corporation
Verification Date June 2019

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