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

NCT03326752 | Completed Phase 1 FDA Drug FDA Device

• 1 other identifier: DV9-NSC-01
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 6

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).

Conditions

Advanced Non Small Cell Lung Cancer

Keywords

Cancer; Lung Cancer; NSCLC; Anti-PD-1 inhibitor; Immuno-oncology; Toll-Like Receptor (TLR) agonist

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Dose Escalation

  IFN response assessment period - Day 1 through Day 21

• Dose Expansion

  1 year after last subject is enrolled in the Dose Expansion phase of study

Study Arms (2)

Dose Escalation Cohort 1-5

EXPERIMENTAL

Cohort 1-4 * DV281 - Dose Level 1-5 * DV281 in combination with nivolumab * DV281 is administered via a breath actuated nebulizer

Drug: DV281; Device: Breath Actuated Nebulizer; Drug: Approved Anti-PD-1 Inhibitor

Dose Expansion (RP2D)

EXPERIMENTAL

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; Drug: DV281 (RP2D); Drug: Approved Anti-PD-1 Inhibitor

Interventions

DV281 DRUG

\- Dose Escalation will be the preliminary dose finding phase of the study. Subjects will be enrolled to available Dosing Cohorts.

Dose Escalation Cohort 1-5

Breath Actuated Nebulizer DEVICE

Breath-actuated, electronic system designed to aerosolize liquid medication.

Also known as: Nebulizer

Dose Escalation Cohort 1-5; Dose Expansion (RP2D)

DV281 (RP2D) DRUG

\- Dose Expansion will be enrolled into 4 groups based on NSCLC characteristics.

Dose Expansion (RP2D)

Approved Anti-PD-1 Inhibitor DRUG

FDA approved Anti-PD-1 Inhibitor

Also known as: nivolumab

Dose Escalation Cohort 1-5; Dose Expansion (RP2D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dynavax Technologies Corporation: lead

Study Sites (6)

Moores UC San Diego Cancer Center

La Jolla, California, 92093, United States

Location

Ronald Reagan University of California Los Angeles Medical Center

Santa Monica, California, 90404, United States

Location

Allina Health, Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37201, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms

Interventions

DV281; Nebulizers and Vaporizers; Nivolumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Equipment and Supplies; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Edward Garon, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: N/A - There is no masking in this study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * 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.

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: October 31, 2017
• Study Start: September 20, 2017
• Primary Completion: September 19, 2019
• Study Completion: September 19, 2019
• Last Updated: June 17, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)