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

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

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).

Study Overview

• Status: Completed
• Conditions: Advanced Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: DV281; Device: Breath Actuated Nebulizer; Drug: Approved Anti-PD-1 Inhibitor; Drug: DV281 (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: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Moores UC San Diego Cancer Center
    • Santa Monica, California, United States, 90404
      • Ronald Reagan University of California Los Angeles Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health, Virginia Piper Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37201
      • Sarah Cannon Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Nebulizer; Drug: Approved Anti-PD-1 Inhibitor; FDA approved Anti-PD-1 Inhibitor; Other Names: 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 Names: Nebulizer; Drug: Approved Anti-PD-1 Inhibitor; FDA approved Anti-PD-1 Inhibitor; Other Names: nivolumab; Drug: DV281 (RP2D); - Dose Expansion will be enrolled into 4 groups based on NSCLC characteristics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation	Incidence of dose-limiting toxicities (DLTs)	DLT assessment period - Day 1 through Day 28.
Dose Expansion	Objective response rate (ORR) of dosing regimen established during the Dose Escalation	1 year after last subject is enrolled in the Dose Expansion phase of study
Dose Expansion	Duration of Response (DOR) and time to response.	1 year after last subject is enrolled in the Dose Expansion phase of the Study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation	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	IFN response assessment period - Day 1 through Day 21
Dose Expansion	Incidence of treatment related AE's as assessed by CTCAE Version 4.03	1 year after last subject is enrolled in the Dose Expansion phase of study

Collaborators and Investigators

• Sponsor: Dynavax Technologies Corporation
• Investigators: Principal Investigator: Edward Garon, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): September 19, 2019
• Study Completion (Actual): September 19, 2019

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): June 17, 2020
• Last Update Submitted That Met QC Criteria: June 15, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; Lung Cancer; NSCLC; Immuno-oncology; Anti-PD-1 inhibitor; Toll-Like Receptor (TLR) agonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nivolumab; Immune Checkpoint Inhibitors
• Other Study ID Numbers: DV9-NSC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes