Phase 1b DV281 With an Anti-PD-1 Inhibitor in NSCLC
- Conditions
- Advanced Non Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03326752
- Lead Sponsor
- 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion (RP2D) DV281 (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. Dose Escalation Cohort 1-5 DV281 Cohort 1-4 * DV281 - Dose Level 1-5 * DV281 in combination with nivolumab * DV281 is administered via a breath actuated nebulizer Dose Escalation Cohort 1-5 Breath Actuated Nebulizer Cohort 1-4 * DV281 - Dose Level 1-5 * DV281 in combination with nivolumab * DV281 is administered via a breath actuated nebulizer Dose Escalation Cohort 1-5 Approved Anti-PD-1 Inhibitor Cohort 1-4 * DV281 - Dose Level 1-5 * DV281 in combination with nivolumab * DV281 is administered via a breath actuated nebulizer Dose Expansion (RP2D) Breath Actuated Nebulizer 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. Dose Expansion (RP2D) Approved Anti-PD-1 Inhibitor 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.
- Primary Outcome Measures
Name Time Method Dose Expansion 1 year after last subject is enrolled in the Dose Expansion phase of the Study Duration of Response (DOR) and time to response.
Dose Escalation DLT assessment period - Day 1 through Day 28. Incidence of dose-limiting toxicities (DLTs)
- Secondary Outcome Measures
Name Time Method Dose Expansion 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
Dose Escalation 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
Trial Locations
- Locations (6)
Moores UC San Diego Cancer Center
🇺🇸La Jolla, California, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Ronald Reagan University of California Los Angeles Medical Center
🇺🇸Santa Monica, California, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Allina Health, Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States