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Poziotinib 在具有 EGFR 或 HER2 外显子 20 插入突变的 NSCLC 患者中的 2 期研究

2026年6月11日 更新者：Spectrum Pharmaceuticals, Inc

Poziotinib 治疗具有 EGFR 或 HER2 外显子 20 插入突变的局部晚期或转移性非小细胞肺癌 (NSCLC) 患者的 2 期研究 (ZENITH20)

这是一项 2 期、开放标签、多中心研究，旨在评估 poziotinib 在七个患者队列中的疗效和安全性/耐受性，涉及多达 603 名既往接受过治疗和未接受过治疗的 NSCLC 患者。 队列 3 和 4 是在修正案 1 中添加的，另外三个队列是在修正案 2 中添加的（队列 5、6 和 7）。

研究概览

地位

终止

条件

干预/治疗

详细说明

筛选期（第 -30 天至第 -1 天）持续至第 1 周期第 1 天之前的大约 30 天。患者必须满足所有纳入/排除标准才能参与研究。 符合条件的患者将在接受任何研究程序之前提供书面知情同意书。

每个治疗周期持续 28 个日历日。 将有七个患者队列，符合条件的患者将根据 EGFR 或 HER2 外显子 20 突变状态和既往治疗状态平行纳入每个队列：

  • 队列 1：先前接受过治疗的 EGFR 外显子 20 插入突变阳性 NSCLC 患者（已停止入组）
  • 队列 2：先前接受过治疗的 HER2 外显子 20 插入突变阳性 NSCLC 患者（已停止入组）
  • 队列 3：EGFR 外显子 20 插入突变阳性 NSCLC 的初治患者（完全入组）
  • 队列 4：HER2 外显子 20 插入突变阳性 NSCLC 的初治患者
  • 队列 5：符合队列 1 至 4 入组标准的患者，但相应队列的入组已结束
  • 队列 6：获得性 EGFR 突变患者在接受一线奥希替尼治疗期间病情进展
  • 队列 7：具有 EGFR 或 HER2 激活突变的患者

将使用 CTCAE 4.03 版根据不良事件的等级评估毒性。

在每个 28 天周期的第 1 天，患者的中性粒细胞绝对计数 (ANC) 必须≥1.5×10^9/L，血小板计数必须≥100×10^9/L，然后才能使用波齐替尼。 所有患者都将接受治疗，直至疾病进展（队列 5 中的首次进展除外）、死亡、无法忍受的不良事件 (AE) 或其他协议规定的患者退出原因。

研究类型

介入性

注册 (实际的)

648

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 以色列
      • Beersheba、以色列
        • Soroka Medical Center
      • Haifa、以色列
        • Rambam Healthcare Campus
      • Jerusalem、以色列
        • Hadassah Medical Center
      • Petah Tikva、以色列
        • Rabin Medical Center
  • 加拿大
    • Alberta
      • Edmonton、Alberta、加拿大、T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Vancouver、British Columbia、加拿大、V5Z 4E6
        • BC Cancer - Vancouver
    • Ontario
      • London、Ontario、加拿大、N6A 5W9
        • London Regional Cancer Program
      • Toronto、Ontario、加拿大、M5G 2M9
        • Princess Margaret Cancer Centre
  • 意大利
      • Milan、意大利
        • National Cancer Institute, IRCCS, Department of Medical Oncology
      • Ravenna、意大利
        • Santa Maria delle Croci Hospital
      • Rome、意大利
        • National Cancer Institute Regina Elena, IRCCS, Operative Unit of Medical Oncology A 1
  • 比利时
      • Brussels、比利时
        • Saint Luc University Hospital
      • Leuven、比利时
        • University Hospitals Leuven
      • Mons、比利时
        • Ambroise Pare University Hospital Center
      • Roeselare、比利时
        • General Hospital Delta
  • 法国
      • Toulouse、法国
        • Hopital Larrey, CHU Toulouse, Unité d'Oncologie des Voies Respiratoires
      • Villejuif、法国
        • Gustave Roussy Oncology Institute, Department of Medical Oncology
  • 美国
    • Arizona
      • Phoenix、Arizona、美国、85054
        • Mayo Clinic Hospital
    • California
      • Arcadia、California、美国、91007
        • Oncology Physician's Network Inc./OPN Healthcare
      • Duarte、California、美国、91010
        • City Of Hope
      • La Jolla、California、美国、92093
        • UCSD -Moores Cancer Center
      • Long Beach、California、美国、90813
        • Pacific Shores Medical Group
      • Los Angeles、California、美国、90017
        • Los Angeles Hematology Oncology Medical Group
      • Los Angeles、California、美国、90033
        • USC/Norris Comprehensive Cancer Center
      • Sacramento、California、美国、95817
        • UC Davis Comprehensive Cancer Center
      • San Francisco、California、美国、94115
        • UCSF Helen Diller Comprehensive Cancer Center at Mt Zion
      • Santa Monica、California、美国、90404
        • UCLA Hematology/Oncology
      • Torrance、California、美国、90502
        • The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
      • Vallejo、California、美国、94589
        • Kaiser Permanente Medical Center
    • Colorado
      • Boulder、Colorado、美国、80303
        • Rocky Mountain Cancer Center
    • Connecticut
      • New Haven、Connecticut、美国、06510
        • Yale University, Yale Cancer Center Smilow Cancer Hospital at Yale
    • District of Columbia
      • Washington D.C.、District of Columbia、美国、20007
        • Georgetown University Medical Center
    • Florida
      • Orlando、Florida、美国、32804
        • Florida Hospital
      • Tampa、Florida、美国、33612
        • H. Lee Moffitt Cancer Center & Research Institute
      • Winter Haven、Florida、美国、33881
        • The Bond & Steele Clinic, P.A. dba Bond Clinic, P.A.
    • Georgia
      • Athens、Georgia、美国、30607
        • University Cancer & Blood Center, LLC
      • Newnan、Georgia、美国、30265
        • CTCA - Southeastern Regional Medical Center
    • Illinois
      • Zion、Illinois、美国、60099
        • CTCA - Midwestern Regional Medical Center
    • Maryland
      • Baltimore、Maryland、美国、21287
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    • Massachusetts
      • Boston、Massachusetts、美国、02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit、Michigan、美国、48201
        • Karmanos Cancer Institute
    • Minnesota
      • Minneapolis、Minnesota、美国、55404
        • Minnesota Oncology Hematology, P.A.
      • Rochester、Minnesota、美国、55905
        • Mayo Clinic
    • Mississippi
      • Hattiesburg、Mississippi、美国、39401
        • Hattiesburg Clinic Hematology/Oncology
    • New York
      • Buffalo、New York、美国、14263
        • Roswell Park Cancer Institute
      • New York、New York、美国、10065
        • Weill Cornell Medical College
      • New York、New York、美国、10016
        • NYU Langone Medical Center
      • Port Jefferson Station、New York、美国、11776
        • North Shore Hematology Oncology Associates P.C. DBA NY Cancer and Blood Specialists
      • The Bronx、New York、美国、10461
        • Montefiore Einstein Medical Center for Cancer Care
      • The Bronx、New York、美国、10469
        • North Shore Hematology Oncology Associates DBA New York Cancer and Blood Specialists
    • North Carolina
      • Durham、North Carolina、美国、27710
        • Duke University Medical Center
    • Ohio
      • Cleveland、Ohio、美国、44195
        • Cleveland Clinic
      • Columbus、Ohio、美国、43210
        • The Ohio State University
    • Oklahoma
      • Tulsa、Oklahoma、美国、74146
        • Oklahoma Cancer Specialists and Research Institute, LLC
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19124
        • CTCA - Eastern Regional Medical Center
    • Tennessee
      • Memphis、Tennessee、美国、38120
        • Baptist Cancer Center
    • Texas
      • Austin、Texas、美国、78745
        • Texas Oncology- Austin
      • Houston、Texas、美国、77030
        • MD Anderson Cancer Center
    • Virginia
      • Fairfax、Virginia、美国、22031
        • Virginia Cancer Specialists, PC
    • Washington
      • Seattle、Washington、美国、98109
        • Seattle Cancer Care Alliance
  • 荷兰
      • Rotterdam、荷兰
        • Erasmus Medical Center
  • 西班牙
      • Barcelona、西班牙
        • University Hospital Germans Trias i Pujol, Department of Medical Oncology
      • Madrid、西班牙
        • University Hospital 12 de Octubre

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

描述

关键纳入标准：

  • 患者必须愿意并能够提供书面知情同意书，遵守剂量和访问时间表，并满足所有研究要求
  • 患者患有经组织学或细胞学证实的局部晚期或转移性非小细胞肺癌 (NSCLC)，不适合以治愈为目的的治疗

  • 既往治疗情况：

    • 第 1 组和第 2 组：患者之前至少接受过一次针对局部晚期或转移性 NSCLC 的全身治疗
    • 第 3 组和第 4 组：患者是局部晚期或转移性 NSCLC 的初治患者，并且有资格接受研究者确定的 poziotinib 一线治疗。 辅助/新辅助疗法（化疗、放疗或研究药物）是允许的，只要它们在研究开始前至少 15 天结束。
    • 队列 5：符合队列 1 至 4 入组标准的患者，但相应队列的入组已结束
    • 队列 6：EGFR 突变阳性 NSCLC 患者在一线奥希替尼治疗期间出现疾病进展
    • 第 7 组：患者之前至少接受过一次针对局部晚期或转移性 NSCLC 的全身治疗

  • 具体突变：

    • 第 1 组和第 3 组：记录在案的 EGFR 外显子 20 插入突变
    • 第 2 组和第 4 组：记录的 HER2 外显子 20 插入突变
    • 队列 5：记录在案的 EGFR 或 HER2 外显子 20 插入突变
    • 队列 6：记录的获得性 EGFR 突变（在奥希替尼进展后测试）
    • 队列 7：记录在案的 EGFR 或 HER2 激活突变
  • 患者在基线时具有足够的器官功能

关键排除标准：

  • 患者在参与研究之前曾接受过 poziotinib 或任何其他 EGFR 或 HER2 外显子 20 插入突变选择性酪氨酸激酶抑制剂 (TKI) 的治疗。 目前批准的 TKI（即厄洛替尼、吉非替尼、阿法替尼、奥希替尼）不被认为是外显子 20 插入选择性的并且是允许的（队列 1 和 2）。
  • 患者同时接受化疗、生物制剂、免疫疗法治疗癌症；不应在 2 周或 5 个半衰期（以较长者为准）内使用全身抗癌治疗或研究性治疗；可以允许对骨痛进行局部放射治疗
  • 患者在过去 3 年内患有其他恶性肿瘤，除了稳定的非黑色素瘤皮肤癌、完全治疗和稳定的早期前列腺癌，或无需治疗的宫颈或乳房原位癌
  • 患者怀孕或哺乳

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Cohort 1: Poziotinib 16 mg
Participants previously treated for epidermal growth factor receptor (EGFR) exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC) received poziotinib, 16 milligrams (mg), orally, once daily (QD) in each 28-day cycle until disease progression, death, intolerable adverse events (AEs), or for up to a maximum of 35 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 2: Poziotinib 16 mg
Participants previously treated for human epidermal growth factor receptor 2 (HER2) exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 32 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 3: Poziotinib 16 mg
Treatment naïve participants with EGFR exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 24 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 4: Poziotinib 8 mg
Treatment naïve participants with HER2 exon 20 insertion mutation-positive NSCLC received poziotinib, 8 mg, orally, twice daily (BID) in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 27 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 4: Poziotinib 16 mg
Treatment naïve participants with HER2 exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 27 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 5: Poziotinib 6 mg
Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 6 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 23 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 5: Poziotinib 8mg
Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 25 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 5: Poziotinib 10 mg
Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 10 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 15 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 5: Poziotinib 12 mg
Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 12 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 26 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 5: Poziotinib 16 mg
Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 18 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 6: Poziotinib 8 mg
Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 29 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 6: Poziotinib 16 mg
Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 7 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 7: Poziotinib 8 mg
Participants with EGFR or HER2 activating mutations received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 20 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。
实验性的：Cohort 7: Poziotinib 16 mg
Participants with EGFR or HER2 activating mutations received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 4 months, whichever occurs first.
药品：泊齐替尼
Poziotinib原料药为poziotinib的盐酸盐，制成口服片剂。

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Objective Response Rate (ORR)
大体时间：Up to 3 years
ORR was defined as the percentage of participants whose best overall response (BOR) was confirmed to be complete response (CR) or partial response (PR) from the first dose of poziotinib until the last tumor assessment on study. ORR was assessed by the Independent Radiologic Review Committee according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all non-nodal target lesions. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present.
Up to 3 years

次要结果测量

结果测量
措施说明
大体时间
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
大体时间：Up to 5 years
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that occur from the first dose of study treatment until 35 (±5) days after the last dose of study treatment.
Up to 5 years
Disease Control Rate (DCR)
大体时间：Up to 3 years
DCR was defined as percentage of participants with best response of CR, PR, or stable disease (SD) from the first dose of poziotinib to the last tumor assessment on study. CR was defined as the disappearance of all non-nodal target lesion. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present. SD was defined as neither sufficient shrinkage of target lesions to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Up to 3 years
Duration of Response (DoR)
大体时间：Up to 3 years
DoR was evaluated only for participants who had CR or PR and was defined as the time from the date that response evaluation criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that PD or death was documented. CR was defined as the disappearance of all non-nodal target lesion. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present. Disease progression was defined as greater than or equal to (≥) 20% increase in the SOD of target lesions taking as reference the nadir SOD (or the baseline, if the baseline is the nadir value). In addition to the relative increase of 20% in SOD, the SOD must also have demonstrated an absolute increase of ≥ 5 mm.
Up to 3 years

其他结果措施

结果测量
措施说明
大体时间
Progression-free Survival (PFS) - Exploratory
大体时间：Up to 3 years
PFS was defined as the time (in months) from the treatment start date to the first date of documented PD or death. Disease progression was defined as ≥20% increase in the SOD of target lesions taking as reference the nadir SOD (or the baseline if the baseline is the nadir value). In addition to the relative increase of 20% in SOD, the SOD must also have demonstrated an absolute increase of ≥ 5 mm.
Up to 3 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Spectrum Pharmaceuticals, Inc

调查人员

  • 研究主任：Lyndah Dreiling, MD、Spectrum Pharmaceuticals, Inc

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2017年10月11日

初级完成 (实际的)

2023年4月3日

研究完成 (实际的)

2023年4月3日

研究注册日期

首次提交

2017年10月10日

首先提交符合 QC 标准的

2017年10月20日

首次发布 (实际的)

2017年10月24日

研究记录更新

最后更新发布 (实际的)

2026年6月12日

上次提交的符合 QC 标准的更新

2026年6月11日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • SPI-POZ-202

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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