Working…
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

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).

Condition or disease Intervention/treatment Phase
Advanced Non Small Cell Lung Cancer Drug: DV281 Device: Breath Actuated Nebulizer Drug: DV281 (RP2D) Drug: Approved Anti-PD-1 Inhibitor Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
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
Official Title: 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
Actual Study Start Date : September 20, 2017
Estimated Primary Completion Date : August 30, 2020
Estimated Study Completion Date : August 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
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
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: Approved Anti-PD-1 Inhibitor
FDA approved Anti-PD-1 Inhibitor
Other Name: nivolumab

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.
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




Primary Outcome Measures :
  1. Dose Escalation [ Time Frame: DLT assessment period - Day 1 through Day 28. ]
    Incidence of dose-limiting toxicities (DLTs)

  2. 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

  3. 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.


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03326752


Locations
Layout table for location information
United States, California
Moores UC San Diego Cancer Center
La Jolla, California, United States, 92093
Ronald Reagan University of California Los Angeles Medical Center
Santa Monica, California, United States, 90404
United States, Minnesota
Allina Health, Virginia Piper Cancer Institute
Minneapolis, Minnesota, United States, 55407
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37201
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Dynavax Technologies Corporation
Investigators
Layout table for investigator information
Principal Investigator: Edward Garon, MD University of California, Los Angeles

Layout table for additonal information
Responsible Party: Dynavax Technologies Corporation
ClinicalTrials.gov Identifier: NCT03326752     History of Changes
Other Study ID Numbers: DV9-NSC-01
First Posted: October 31, 2017    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Keywords provided by Dynavax Technologies Corporation:
Cancer
Lung Cancer
NSCLC
Anti-PD-1 inhibitor
Immuno-oncology
Toll-Like Receptor (TLR) agonist
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents