A Phase 1/2, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of BBT-176 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Progressed Following Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Agent
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 45
- 试验地点
- 4
- 主要终点
- (Part 1) Incidence of Adverse Events and Clinical Laboratory Abnormalities Defined as Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This clinical trial is the first-in-human study of BBT-176. The purpose of this trial is to investigate the safety and tolerability of BBT-176 (Part 1) and to evaluate the anti-tumor activity of BBT-176 (Part 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Provision of signed and dated, written informed consent before any study specific procedures, sampling and analyses
- •Histological or cytological confirmation of advanced and/or metastatic stage IIIB/IV NSCLC
- •Radiological documentation of disease progression while on a previous continuous (at least 30 days) treatment with an EGFR TKI monotherapy (including, but not limited to, osimertinib, afatinib, gefitinib, or erlotinib)
- •Patients must fulfill one of the following:
- •Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including, but not limited to, exon 19 deletion, L858R, or L861Q)
- •Documented partial or complete response or a significant and durable stable disease (at least 6 months), based on the RECIST or WHO criteria, after treatment of an EGFR TKI
排除标准
- •Treatment with any of the following:
- •An EGFR TKI, including but not limited to osimertinib, afatinib, gefitinib, or erlotinib within 8 days of the first dose of study treatment.
- •Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for the treatment of advanced NSCLC, between prior EGFR TKI treatment and BBT-176 treatment
- •Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
- •Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment
- •Patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation within 6 weeks of the first dose of study treatment
- •Any unresolved toxicities from prior therapy greater than NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 neuropathy related to prior platinum-therapy
- •Spinal cord compression or brain metastases, unless asymptomatic and stable
研究组 & 干预措施
20mg QD
BBT-176: 20mg, Orally, Once daily (QD)
干预措施: BBT-176, QD (Drug)
80mg QD
BBT-176: 80mg, Orally, QD
干预措施: BBT-176, QD (Drug)
160mg QD
BBT-176: 160mg, Orally, QD
干预措施: BBT-176, QD (Drug)
320mg QD
BBT-176: 320mg, Orally, QD
干预措施: BBT-176, QD (Drug)
480mg QD
BBT-176: 480mg, Orally, QD
干预措施: BBT-176, QD (Drug)
600mg QD
BBT-176: 600mg, Orally, QD
干预措施: BBT-176, QD (Drug)
160mg, BID
BBT-176: 160mg, Orally, Twice daily (BID)
干预措施: BBT-176, BID (Drug)
200mg, BID
BBT-176: 200mg, Orally, BID
干预措施: BBT-176, BID (Drug)
240mg, BID
BBT-176: 240mg, Orally, BID
干预措施: BBT-176, BID (Drug)
结局指标
主要结局
(Part 1) Incidence of Adverse Events and Clinical Laboratory Abnormalities Defined as Dose-limiting Toxicities (DLTs)
时间窗: 21 days from the first dosing
Any toxicity not attributable to the disease or disease-related processes under investigation that occurs from the first dose of study treatment in dose-escalation cohorts as defined in the protocol.
(Part 2) Objective Response Rate (ORR)
时间窗: Every 6 weeks
ORR is estimated by the number of patients with a best overall response of CR or PR divided by the total number of patients who are evaluable for efficacy.
次要结局
- (Part 1) Pharmacokinetics (PK) Parameters - Peak Concentration (Cmax)(0, 1, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1) (each cycle is 21 days))
- (Part 1) PK Parameters - Area Under the Concentration-time Curve (AUC)(0, 1, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1) (each cycle is 21 days))
- (Part 1) Objective Response Rate (ORR)(Every 6 weeks, approximately 1 year)
- (Part 2) Duration of Response (DoR)(throughout study completion, approximately 1 year)
- (Part 2) Incidence of Adverse Event (AE)s(throughout study completion, approximately 1 year)
- (Part 2) BBT-176 Concentrations(At Cycle 2 Day 1 (each cycle is 21 days))
- (Part 2) Progression Free Survival (PFS)(throughout study completion, approximately 1 year)