NCT03326752已完成1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 6
- 主要终点
- Dose Expansion
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
N/A - There is no masking in this study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation Cohort 1-5
Experimental
Cohort 1-4
- DV281 - Dose Level 1-5
- DV281 in combination with nivolumab
- DV281 is administered via a breath actuated nebulizer
干预措施: DV281 (Drug)
Dose Escalation Cohort 1-5
Experimental
Cohort 1-4
- DV281 - Dose Level 1-5
- DV281 in combination with nivolumab
- DV281 is administered via a breath actuated nebulizer
干预措施: Breath Actuated Nebulizer (Device)
Dose Escalation Cohort 1-5
Experimental
Cohort 1-4
- DV281 - Dose Level 1-5
- DV281 in combination with nivolumab
- DV281 is administered via a breath actuated nebulizer
干预措施: Approved Anti-PD-1 Inhibitor (Drug)
Dose Expansion (RP2D)
Experimental
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.
干预措施: Breath Actuated Nebulizer (Device)
Dose Expansion (RP2D)
Experimental
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.
干预措施: DV281 (RP2D) (Drug)
Dose Expansion (RP2D)
Experimental
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.
干预措施: Approved Anti-PD-1 Inhibitor (Drug)
结局指标
主要结局
Dose Expansion
时间窗: 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
时间窗: DLT assessment period - Day 1 through Day 28.
Incidence of dose-limiting toxicities (DLTs)
次要结局
- Dose Expansion(1 year after last subject is enrolled in the Dose Expansion phase of study)
- Dose Escalation(IFN response assessment period - Day 1 through Day 21)
研究者
研究点 (6)
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