NCT06905197招募中1 期
A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Efficacy of DZD6008 in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations (TIAN-SHAN1)
Dizal Pharmaceuticals5 个研究点 分布在 2 个国家目标入组 70 人开始时间: 2025年5月13日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 70
- 试验地点
- 5
- 主要终点
- Part A: To assess safety and tolerability
研究概览
简要总结
This study is designed to evaluate safety and anti-tumor activity of DZD6008 in patients with advanced NSCLC with EGFR mutations.
详细描述
The study includes two parts: Part A (dose escalation) and Part B(dose expansion). In Part A, locally advanced or metastatic NSCLC patients with EGFR sensitizing mutations (Exon19del and/or L858R) following at least 1 prior EGFR TKI regimen will be enrolled. In Part B, locally advanced or metastatic NSCLC patients with EGFR sensitizing mutations following 1 line of the third generation of EGFR TKI treatment will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Patients must be able to provide documented informed consent.
- •Aged ≥ 18 years.
- •Histologically or cytologically confirmed diagnosis of NSCLC, locally advanced or metastatic, not suitable for curative therapy.
- •Documentation of EGFR sensitizing mutations (Exon19del and/or L858R) from a local CLIA-certified laboratory (or equivalent).
- •Provide adequate amount of pretreatment tumor samples collected after disease progression on the last EGFR TKI treatment.
- •Failed (progressed or are intolerant) from at least 1 prior EGFR TKI regimen.
- •ECOG 0 or 1 with predicted life expectancy ≥ 12 weeks.
- •Patients with brain metastases must have a stable BM status.
- •Measurable disease per RECIST 1.
- •Adequate hematopoietic and other organ system functions.
- •Male Patients with female partners of childbearing potential should use barrier contraceptives and refrain from donating sperm during their participation in this study and for 3 months following the last dose of the study drug.
排除标准
- •Carry any other known EGFR alterations, including but not limited to uncommon EGFR mutations (G719X, S768I, L861Q, exon 20 insertions, etc.)(Part B).
- •NSCLC with mixed small cell lung cancer (SCLC) or NSCLC with histologic SCLC transformation.
- •Prior treatment with any of the following: 1)Immunotherapy or other antibody therapy within 4 weeks prior to the first administration; 2)Any cytotoxic chemotherapy, investigational drugs or other anticancer drugs from a previous treatment regimen or clinical study within 14 days prior to the first administration; 3)Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose, radiation to more than 30% of the bone marrow or with a wide field of radiation within 28 days before screening; 4)Currently receiving or unable to stop drug or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP)3A
- •A washout period of at least 2 weeks for strong inhibitors and 3 weeks for strong inducers is required prior to the first study drug administration; 5)currently receiving or unable to stop drugs known to be CYP3A4 sensitive substrate with a narrow therapeutic index. A washout period of at least 14 days is required prior to the first study drug administration; 6)currently receiving or unable to stop drugs known to be proton pump inhibitors. A washout period of at least 7 days is required prior to the first study drug administration; 7)major surgery within 4 weeks of the first administration of DZD6008 or anticipated during the study period.
- •Any unresolved toxicities from prior anti-cancer therapy greater than CTCAE Grade
- •Spinal cord compression or leptomeningeal metastasis.
- •Patients with any other malignancy within 2 years of the first administration of study drug.
- •Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses as judged by investigator.
- •Patients with active infection, including but not limited to HBV, HCV, HIV and active infection of COVID-
- •Resting QTcF > 470 msec; Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG;Any factors that increase the risk of QTc prolongation.
- •Past medical history of ILD or active ILD.
- •Diseases which would preclude adequate absorption of DZD
- •Received a live vaccine within 2 weeks before the first administration of DZD
- •Women who are pregnant or breastfeeding.
- •Hypersensitivity to active or inactive excipients of DZD
- •Involvement in the planning and conduct of the study.
- •Judgment by the investigator that the patient is unlikely to comply with study procedures
研究组 & 干预措施
Experimental: Part A Dose Escalation cohorts (120 mg QD)
Experimental
干预措施: DZD6008 (Drug)
Experimental: Part A Dose Escalation cohorts (150 mg QD)
Experimental
干预措施: DZD6008 (Drug)
Experimental: Part A Dose Escalation cohorts (20 mg once daily [QD])
Experimental
干预措施: DZD6008 (Drug)
Experimental: Part A Dose Escalation cohorts (40 mg QD)
Experimental
干预措施: DZD6008 (Drug)
Experimental: Part A Dose Escalation cohorts (60 mg QD)
Experimental
干预措施: DZD6008 (Drug)
Experimental: Part A Dose Escalation cohorts (90 mg QD)
Experimental
干预措施: DZD6008 (Drug)
Experimental: Part B Dose Expansion cohorts (selected dose 1 QD)
Experimental
干预措施: DZD6008 (Drug)
Experimental: Part B Dose Expansion cohorts (selected dose 2 QD)
Experimental
干预措施: DZD6008 (Drug)
结局指标
主要结局
Part A: To assess safety and tolerability
时间窗: Through the study completion, an average of around 1 year
Number of participants with Adverse events (AEs)/Serious adverse events (SAEs)
Part B: To assess anti-tumor activity
时间窗: Through the study completion, an average of around 1 year
Objective Response Rate (ORR) assessed by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
次要结局
- Part A: To characterize the plasma concentration of DZD6008 following single and multiple oral dose administration(From first dosing to cycle 7 day 1, each cycle is 21 days)
- Part A: To assess the anti-tumor activity(Through the study completion, an average of around 1 year)
- Part B: To assess the anti-tumor activity(PFS assessed by IRC and investigators per RECIST version 1.1)
- Part B: Plasma concentration of DZD6008(Time Frame: From first dosing to cycle 11 day 1, each cycle is 21 days)
- Part B: To assess safety and tolerability(Through the study completion, an average of around 1 year)
研究者
研究点 (5)
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