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History of Changes for Study: NCT03326752
Phase 1b DV281 With an Anti-PD-1 Inhibitor in NSCLC
Latest version (submitted June 15, 2020) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 October 25, 2017 None (earliest Version on record)
2 November 2, 2017 Outcome Measures, Arms and Interventions, Study Status and Study Identification
3 February 27, 2018 Study Status and Contacts/Locations
4 May 17, 2018 Contacts/Locations and Study Status
5 October 12, 2018 Contacts/Locations, Arms and Interventions, Study Design, Study Description, Study Status, Eligibility and Outcome Measures
6 January 30, 2019 Contacts/Locations and Study Status
7 March 18, 2019 Contacts/Locations and Study Status
8 June 10, 2019 Recruitment Status, Study Status, Contacts/Locations and Study Design
9 June 15, 2020 Recruitment Status and Study Status
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Changes (Merged) for Study: NCT03326752
May 17, 2018 (v4) -- October 12, 2018 (v5)

Changes in: Study Status, Study Description, Study Design, Arms and Interventions, Outcome Measures, Eligibility and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: DV9-NSC-01
Brief Title: Phase 1b DV281 With an Anti-PD-1 Inhibitor in NSCLC
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
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2018 October 2018
Overall Status: Recruiting
Study Start: September 20, 2017
Primary Completion: August 30, 2020 [Anticipated]
Study Completion: August 30, 2020 [Anticipated]
First Submitted: October 19, 2017
First Submitted that
Met QC Criteria:
October 25, 2017
First Posted: October 31, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
May 17, 2018 October 12, 2018
Last Update Posted: May 21 October 16, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Dynavax Technologies Corporation
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: Yes
Unapproved/Uncleared Device:
Pediatric Postmarket Surveillance:
Data Monitoring: No
Open or close this module Study Description
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 an approved anti-PD-1 inhibitor for 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 an approved anti-PD-1 inhibitor 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.
Open or close this module Conditions
Conditions: Advanced Non Small Cell Lung Cancer
Keywords: Cancer
Lung Cancer
NSCLC
Anti-PD-1 inhibitor
Immuno-oncology
Toll-Like Receptor (TLR) agonist
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
  • 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 , dependent on the maximum tolerated dose (MTD) of DV281 in the Dose Escalation phase of the study combination with an approved anti-PD-1 inhibitor.
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 80 167 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Dose Escalation Cohort 1-5

Cohort 1- 5 4

  • DV281 - Dose Level 1-5
  • DV281 in combination with approved anti-PD-1 Inhibitor. 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 Names:
  • Nebulizer
Approved Anti-PD-1 Inhibitor - Escalation
FDA approved anti PD-1 Inhibitor
Drug: Approved Anti-PD-1 Inhibitor
FDA approved Anti-PD-1 Inhibitor
Other Names:
  • nivolumab
Experimental: Dose Expansion (RP2D)

Preliminary Recommended Phase 2 dosing of DV281 in combination with an approved anti-PD-1 Inhibitor 4 Cohorts

  • - DV281 is administered via a breath actuated nebulizer. 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 Names:
  • Nebulizer
Drug: DV281 (RP2D)
- Dose Expansion will be enrolled into 2 groups, specifically, anti-PD-1/L1 treatment naïve and anti-PD-1/L1 treatment experienced. - Dose Expansion will be enrolled into 4 groups based on NSCLC characteristics.
Device: Breath Actuated Nebulizer
Breath-actuated, electronic system designed to aerosolize liquid medication.
Drug
Approved Anti-PD-1 Inhibitor - Expansion
FDA approved Anti-PD-1 Inhibitor
Other Names:
  • nivolumab
Open or close this module Outcome Measures
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
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Have documented histologically or cytologically confirmed advanced NSCLC with no small cell as the dominant histology or neuroendocrine histology .
  • Have progressed on prior systemic therapy If confirmed EGFR or ALK directed testing warrants actionable targeted therapy, must have confirmed disease progression on targeted therapy or cannot tolerate targeted therapy.
  • Have PD-L1 expression level determined from the subject's archival tissue or fresh tumor specimen Aged 18 years and older on the day of signing informed consent
  • 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
  • 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
  • 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
  • Has extensive pleural effusion which occupies greater than 50% of the total lung volume observed on screening imaging
  • 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
  • Received small molecule targeted therapy such as TKIs within 2 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 active central nervous system metastases, brain metastases, or carcinomatous meningitis
Open or close this module Contacts/Locations
Central Contact Person: Graciela Perez
Telephone: 619-293-6237
Email: PerezGraciela@prahs.com
Central Contact Backup: Erick Gamelin, MD M.D., PhD
Telephone: 510-665-0470
Email: egamelin@dynavax.com
Study Officials: Edward Garon, MD
Principal Investigator
University of California, Los Angeles
Locations: United States, California
Please contact Dynavax Technologies for any questions
[Not yet recruiting]
La Jolla, California, United States, 92093
United States, California
Please contact Dynavax Technologies for any questions Ronald Reagan University of California Los Angeles Medical Center
[Recruiting]
Santa Monica, California, United States, 90404
United States, Minnesota
Allina Health, Virginia Piper Cancer Institute
[Recruiting]
Minneapolis, Minnesota, United States, 55407
United States, Tennessee
Please contact Dynavax Technologies for any questions Sarah Cannon Research Institute
[Recruiting]
Nashville, Tennessee, United States, 37201
United States, Virginia
Please contact Dynavax Technologies for any questions Virginia Cancer Specialists
[Recruiting]
Fairfax, Virginia, United States, 22031
United States, Washington
Please contact Dynavax Technologies for any questions Seattle Cancer Care Alliance
[Recruiting]
Seattle, Washington, United States, 98109
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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