Phase I Trial of Atezolizumab and Interleukin-12 Gene Therapy in Metastatic Non-Small Cell Lung Cancer With Progression on First-Line Immunotherapy With or Without Chemotherapy
概览
- 阶段
- 1 期
- 干预措施
- 未指定
- 疾病 / 适应症
- Non-small Cell Lung Cancer
- 发起方
- The Methodist Hospital Research Institute
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Progression-free survival plus stable disease after 6 cycles
- 状态
- 终止
- 最后更新
- 上个月
概览
简要总结
This is a Phase I study evaluating the safety of atezolizumab in combination with ADV/IL-12 gene therapy in patients with metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on first-line immunotherapy with or without chemotherapy.
详细描述
This is a Phase I study evaluating the safety of atezolizumab in combination with adenoviral-mediated interleukin-12 (ADV/IL-12) gene therapy in patients with metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on first-line immunotherapy with or without chemotherapy. Approximately 16 patients will be enrolled on the study. The primary endpoint will be the safety of the atezolizumab and ADV/IL-12 gene therapy combination and will be determined using the Bayesian model averaging-continual reassessment method (BMA-CRM). ADV/IL-12 will be intratumorally injected on Day 0 of the study. The starting dose of ADV/IL-12 will be 5 × 1011 vp. ADV/IL-12 dose level will de-escalate based on Dose Limiting Toxicity (DLT) occurrence: dose level -1, 3 × 1011 vp and dose level -2, 1 × 1011 vp. The starting dose, based on the dose range explored in prior studies, is expected to have activity and dosing changes are only in place in the event that toxicity is demonstrated. Starting on Day 2 of the study, atezolizumab will be administered at 1200 mg IV every 3 weeks (Q3W) for 2 cycles. Patients with stable disease or better after completion of 2 cycles of atezolizumab will continue to receive atezolizumab Q3W until disease progression, unacceptable toxicity, or up to 12 months.
研究者
Jun Zhang
Associate Professor of Clinical Medicine in Oncology
The Methodist Hospital Research Institute
入排标准
入选标准
- •Patients must meet the following criteria for study entry:
- •Signed informed consent form.
- •Male or female.
- •Age ≥ 18 years at time of signing informed consent form.
- •Ability to comply with the study protocol, in the investigator's judgment.
- •Histologically or cytologically confirmed metastatic NSCLC.
- •Disease progression on first-line immunotherapy with or without chemotherapy (chemoimmunotherapy \[e.g., carboplatin/pemetrexed/pembrolizumab\] or single-agent pembrolizumab in PD-L1-expressing tumors). Patients with National Comprehensive Cancer Network recommended targeted mutations who have failed FDA-approved targeted therapies for these aberrations will be eligible for enrollment in the study.
- •Measurable disease per RECIST v1.
- •Previously irradiated lesions can be considered as measurable disease only if progressive disease (PD) has been unequivocally documented at that site since radiation.
- •Accessible tumor for ADV/IL-12 administration (a lesion safely accessible by an image guided biopsy or bronchoscopy) .
排除标准
- •Patients who meet any of the following criteria will be excluded from study entry:
- •History of leptomeningeal disease.
- •Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry Palliative radiotherapy is allowed to a single painful metastatic site during the study if the patient is otherwise benefitting from the study treatment per the treating physician's judgment.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX®) are allowed.
- •Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12 mg/dL or corrected serum calcium \>ULN).
- •Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- •Rash must cover \<10% of body surface area
- •Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- •No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), druginduced pneumonitis, or idiopathic pneumonitis History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
结局指标
主要结局
Progression-free survival plus stable disease after 6 cycles
时间窗: 12 weeks
The primary efficacy endpoint will be the progression-free survival (complete response, partial response) plus stable disease after 6 cycles of atezolizumab) of patients treated with atezolizumab and IL-12 gene therapy in metastatic non-small cell lung cancer with progression on first-line immunotherapy with or without chemotherapy.
次要结局
- Patient-reported outcomes (PRO)(12 weeks)
- Overall Survival(12 weeks)
- Radiographic response rate(12 Weeks)
- Health-Related Quality-of-Life (HRQOL)(12 weeks)