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

NCT ID: NCT03326752

Last Updated: 2020-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-20
• Study Completion Date: 2019-09-19

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.

Conditions

Advanced Non Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

DV281

Intervention Type: DRUG

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

Breath Actuated Nebulizer

Intervention Type: DEVICE

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

Approved Anti-PD-1 Inhibitor

Intervention Type: DRUG

FDA approved Anti-PD-1 Inhibitor

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.

Group Type: EXPERIMENTAL

Breath Actuated Nebulizer

Intervention Type: DEVICE

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

DV281 (RP2D)

Intervention Type: DRUG

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

Approved Anti-PD-1 Inhibitor

Intervention Type: DRUG

FDA approved Anti-PD-1 Inhibitor

Interventions

DV281

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

Intervention Type: DRUG

Breath Actuated Nebulizer

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

Intervention Type: DEVICE

DV281 (RP2D)

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

Intervention Type: DRUG

Approved Anti-PD-1 Inhibitor

FDA approved Anti-PD-1 Inhibitor

Intervention Type: DRUG

Other Intervention Names

Nebulizer; nivolumab

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dynavax Technologies Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward Garon, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

Moores UC San Diego Cancer Center

La Jolla, California, United States

Ronald Reagan University of California Los Angeles Medical Center

Santa Monica, California, United States

Allina Health, Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

Other Identifiers

DV9-NSC-01

Identifier Type: -

Identifier Source: org_study_id