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

Advanced Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03326752
• Other study ID #: DV9-NSC-01
• Status: Completed
• Phase: Phase 1
• Start date: September 20, 2017
• Est. completion date: September 19, 2019

Study information

• Verified date: June 2020
• Source: Dynavax Technologies Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 19, 2019
• Est. primary completion date: September 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Non Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• DV281
- Dose Escalation will be the preliminary dose finding phase of the study. Subjects will be enrolled to available Dosing Cohorts.

Device:
• Breath Actuated Nebulizer
Breath-actuated, electronic system designed to aerosolize liquid medication.

Drug:
• DV281 (RP2D)
- Dose Expansion will be enrolled into 4 groups based on NSCLC characteristics.
• Approved Anti-PD-1 Inhibitor
FDA approved Anti-PD-1 Inhibitor

Locations

Country	Name	City	State
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Moores UC San Diego Cancer Center	La Jolla	California
United States	Allina Health, Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Ronald Reagan University of California Los Angeles Medical Center	Santa Monica	California
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Dynavax Technologies Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation	Incidence of dose-limiting toxicities (DLTs)	DLT assessment period - Day 1 through Day 28.
Primary	Dose Expansion	Objective response rate (ORR) of dosing regimen established during the Dose Escalation	1 year after last subject is enrolled in the Dose Expansion phase of study
Primary	Dose Expansion	Duration of Response (DOR) and time to response.	1 year after last subject is enrolled in the Dose Expansion phase of the Study
Secondary	Dose Escalation	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	IFN response assessment period - Day 1 through Day 21
Secondary	Dose Expansion	Incidence of treatment related AE's as assessed by CTCAE Version 4.03	1 year after last subject is enrolled in the Dose Expansion phase of study