Clinical trial NCT03326752: Phase 1b DV281 With an Anti-PD-1 Inhibitor in NSCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Non Small Cell Lung Cancer
Keywords: Cancer
Lung Cancer
NSCLC
Anti-PD-1 inhibitor
Immuno-oncology
Toll-Like Receptor (TLR) agonist
Lead sponsor: Dynavax Technologies Corporation
Sponsor class: INDUSTRY
First posted: 2017-10-31
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Dose Escalation
timeFrame: DLT assessment period - Day 1 through Day 28.
measure: Dose Expansion
timeFrame: 1 year after last subject is enrolled in the Dose Expansion phase of study
measure: Dose Expansion
timeFrame: 1 year after last subject is enrolled in the Dose Expansion phase of the Study
Secondary outcomes:
measure: Dose Escalation
timeFrame: IFN response assessment period - Day 1 through Day 21
measure: Dose Expansion
timeFrame: 1 year after last subject is enrolled in the Dose Expansion phase of study
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: Santa Monica
country: United States
facility: Ronald Reagan University of California Los Angeles Medical Center
state: California
city: Minneapolis
country: United States
facility: Allina Health, Virginia Piper Cancer Institute
state: Minnesota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: University of California, Los Angeles
name: Edward Garon, MD
role: PRINCIPAL_INVESTIGATOR
References: