Antitumor Activity and Safety of BEBT-109, a Novel EGFR Inhibitor, in Previously Treated NSCLC With EGFR Exon 20 Insertion Mutations: a Phase 1B, Dose Escalation and Expansion Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- DLT
研究概览
简要总结
This clinical study was a first-in-human, phase 1B, single-center, single-arm, open-label, dose escalation and expansion trial that aimed to determine the safety, tolerability and efficacy of BEBT-109 in patients with locally advanced or metastatic NSCLC harboring EGFR exon20ins mutations who had received at least one line of previous treatment.
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
- Single (Outcomes Assessor)
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
- •Sign written informed consent before implementing any trial-related procedures;
- •Age ≥18 years and no limit on the gender.
- •Histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR exon20ins mutation according to assessments made in local laboratories.
- •Previous treatment and type of mutation:
- •Disease progression in doses extension cases may have been treated with an EGFR-TKI (e.g., gefitinib, erlotinib, eclitinib, afatinib, or dapatinib) and prior written test reports confirming EGFR T790M mutation.
- •Disease progression after prior chemotherapy regimen and/or EGFR-TKI treatment in dose-extension cases, and prior written test reports confirming EGFR 20 exon insertion mutations.
- •Disease progression following prior chemotherapy regimen and/or EGFR-TKI treatment in dose-extension cases, and prior written test reports confirming other rare mutations in EGFR (EGFR G719A, L861Q, or S768I point mutations).
- •Patients who are intolerant to chemotherapy or EGFR-TKI and have no other effective treatment can also be admitted to the dose expansion group after judgment by the investigator.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Patients with brain metastasis were only enrolled if the metastases were stable.
- •Subjects had at least 1 measurable lesion that met the RECIST 1.1 criteria.
- •If female subjects are of childbearing potential, adequate contraception (e.g., condoms, etc.) should be used, no breastfeeding should be used, and a negative pregnancy test before administration should be given.
排除标准
- •Combined with any other malignancy (except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix).
- •Genetic testing confirmed the presence of C-MET amplification, HER-2 amplification and KRAS mutations, and other genetic mutations that clearly confirm resistance to EGFR-TKI.
- •From the last treatment of EGFR-TKI (such as erlotinib, gefitinib, eclitinib, afatinib or osimertinib, etc.) to the first administration of this clinical trial, the interval is less than 14 days or 5 half-lives (whichever is longer is the exclusion criterion), and the specific drugs involved are decided by the investigator based on comprehensive consideration.
- •In the 4 weeks prior to the first administration of the study treatment, participants had used other anticancer drugs (including immune cell therapy) in the previous treatment regimen.
- •Those who have not withdrawn from other clinical trials within 4 weeks prior to the first administration of the study treatment.
- •Previous homogeneous drug restriction:
- •Patients with EGFR mutation previously treated with osimertinib or other third-generation EGFR inhibitor drugs (eg, ivelitinib, emetinib, and eflotinib) ;
- •EGFR exon20 insertion mutants have used drugs that target EGFR 20 exon insertion mutants (e.g. Poziotinib tarloxotinib TAK788 JNJ-61186372 CLN-081, etc.)
- •Other EGFR rare mutations (EGFR G719A, L861Q, or S768I point mutations) have been treated with afatinib.
研究组 & 干预措施
BEBT-109 120mg
BEBT-109 orally at an initial dose of 120 mg once daily.
干预措施: BEBT-109 (Drug)
BEBT-109 180mg
BEBT-109 orally at an initial dose of 180 mg once daily.
干预措施: BEBT-109 (Drug)
BEBT-109 240mg
BEBT-109 orally at an initial dose of 240mg (120mg bid) once daily.
干预措施: BEBT-109 (Drug)
结局指标
主要结局
DLT
时间窗: 2 years
Defined as one of adverse events defined by NCI CTCAE V5.0 from the first day to the 28th day of the treatment period.
MTD
时间窗: 2 years
If only 1 of 3 participants in a dose group has DLT, 3 additional subjects in this group will be tested at the same dose level; If no participants developed DLT, the next dose study was conducted; If 2 of the first 3 participants developed DLT or 2 of 6 participants developed DLT, the previous dose of the dose was the maximum tolerated dose (MTD).
次要结局
- DCR(2 years)
- ORR(2 years)
研究者
Yongchang Zhang
Professor, Deputy Director of Thoracic Oncology Department
Hunan Province Tumor Hospital