Advanced Non Small Cell Lung Cancer
Conditions
Keywords
Cancer, Lung Cancer, NSCLC, Anti-PD-1 inhibitor, Immuno-oncology, Toll-Like Receptor (TLR) agonist
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.
Interventions
DRUGDV281
\- Dose Escalation will be the preliminary dose finding phase of the study. Subjects will be enrolled to available Dosing Cohorts.
Breath-actuated, electronic system designed to aerosolize liquid medication.
DRUGDV281 (RP2D)
\- Dose Expansion will be enrolled into 4 groups based on NSCLC characteristics.
DRUGApproved Anti-PD-1 Inhibitor
FDA approved Anti-PD-1 Inhibitor
Sponsors
Dynavax Technologies Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
N/A - There is no masking in this study.
Intervention model description
* 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation | DLT assessment period - Day 1 through Day 28. | Incidence of dose-limiting toxicities (DLTs) |
| Dose Expansion | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
United States
Outcome results
None listed