Phase 3, Two-stage, Randomized Study of ONC-392 Versus Docetaxel in Metastatic Non-Small Cell Lung Cancers That Progressed on PD-1/PD-L1 Inhibitors
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- OncoC4, Inc.
- 入组人数
- 630
- 试验地点
- 304
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The goal of this Phase 3 clinical trial is to study the safety and efficacy of the nextgen anti-CTLA-4 antibody, gotistobart (ONC-392/BNT316), in patients with metastatic non-small cell lung cancer who have disease progressed on anti-PD-1/PD-L1 antibody based therapy. The study will test whether gotistobart, in comparison with chemotherapy agent docetaxel, could prolong the life for NSCLC patients. Patients will be randomized to be treated with either gotistobart or docetaxel, IV infusion, once every 21 days, for up to 17 cycles in approximately one year.
详细描述
This is a seamless 2-stage, randomized, open-label, active-controlled, Phase 3 study. The study population consists of patients with NSCLC who progressed on PD-1/PD-L1 inhibitor. Approximately 630 patients will be enrolled.
Two gotistobart dosing regimens will be tested in Stage I, and one will be selected for Stage II.
Stage I, the dose-confirmation stage, will assess the efficacy and safety of two gotistobart dosing regimens (3 mg/kg Q3W and 6 mg/kg Q3W with 2 loading doses of 10 mg/kg Q3W) in comparison to docetaxel 75 mg/m2 Q3W.
Stage II will assess the safety and efficacy of gotistobart at the selected dosing regimen versus docetaxel on squamous cell NSCLC. Patients will be randomized 1:1 to receive either gotistobart at the selected dosing regimen or docetaxel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •(Major criteria):
- •Adult (≥ 18 years), all genders, capable of signing informed consent.
- •Histologically- or cytologically- confirmed diagnosis of metastatic squamous NSCLC, metastasis can be regional lymph nodes or distant organs.
- •Radiographic progression after treatment with the most recent line of treatment being either 3a or 3b:
- •At least 12 weeks of PD-1/PD-L1 inhibitor in combination with platinum-based chemotherapy;
- •Prior treatment with at least 2 cycles of a platinum-based chemotherapy, followed by at least 12 weeks of standard doses of PD-1 or PD-L1 inhibitor-based immunotherapy.
- •Antibodies against CTLA-4, LAG-3, TIGIT, VEGF or VEGFR in combination with PD-1/PD-L1 inhibitor are allowed.
- •At least one measurable tumor lesion according to RECIST 1.
- •ECOG score of 0 or
- •Adequate organ functions. Serum LDH level ≤ 2xULN.
- •Life expectancy ≥ 3 months.
排除标准
- •(Major criteria):
- •Cancer treatment related AEs have not recovered to NCI CTCAE grade≤ 1 except endocrinopathy.
- •Last anti-PD-1/PD-L1 dosing within 28 days prior to first dose of study treatment.
- •Receiving systemic steroid therapy with >10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment.
- •Having documented actionable mutations or genomic alterations in any of the following genes: EGFR, ALK, ROS1, HER2, MET, BRAF, RET or NTRK;. Exception: KRAS mutations are not excluded.
- •Patients who have symptomatic brain metastasis. Palliative radiotherapy or radiosurgery to brain metastasis within 14 days of the first dose of study drug.
- •Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
- •Active interstitial lung disease (ILD) or non-infectious pneumonitis.
- •Active infections with IV antibiotics within 14 days prior to first dose of study treatment.
- •Impaired heart function.
研究组 & 干预措施
Arm 1: Gotistobart 6 mg/kg with 2 loading doses of 10 mg/kg, Q3W
Gotistobart will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.
干预措施: Gotistobart (Drug)
Arm 2: Docetaxel 75 mg/m2, Q3W
Docetaxel will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: 36 months
OS is defined as the time from randomization to the date of death by any cause. Kaplan-Meier estimates of median OS time will be presented by treatment arm with two sided 95% CIs.
次要结局
- Progression-free survival (PFS)(36 months)
- Objective response rate (ORR)(36 months)
- Treatment emergent adverse events, treatment related adverse events and immune related adverse events.(36 months)