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

Dynavax Technologies Corporation

Status and phase: Completed; Phase 1

Conditions: Advanced Non Small Cell Lung Cancer

Treatments: Device: Breath Actuated Nebulizer; Drug: Approved Anti-PD-1 Inhibitor; Drug: DV281; Drug: DV281 (RP2D)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03326752

DV9-NSC-01

Details and patient eligibility

About

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).

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Dose Escalation Cohort 1-5

Experimental group

Description:

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

Treatment:

Drug: DV281

Drug: Approved Anti-PD-1 Inhibitor

Device: Breath Actuated Nebulizer

Dose Expansion (RP2D)

Experimental group

Description:

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.

Treatment:

Drug: DV281 (RP2D)

Drug: Approved Anti-PD-1 Inhibitor

Device: Breath Actuated Nebulizer