First-In-Human Study of STX-721/PFL-721 in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR or HER2 Exon 20 Insertion Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 345
- 试验地点
- 41
- 主要终点
- Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
研究概览
简要总结
Study STX-721-101/PFL-721CI101 is an open label, Phase 1/2 study evaluating the safety, tolerability, pharmacokinetic (PK) exposure, and preliminary antitumor activity of STX-721/PFL-721 in participants with non-small cell lung cancer (NSCLC) carrying EGFR or HER2 exon 20 insertion (ex20ins) mutations.
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
- 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
- •Has histologically- or cytologically confirmed diagnosis of NSCLC Stage IIIB/C or IV not eligible for curative intent surgery or chemoradiation
- •Part 1: Tumor tissue EGFR or HER2 exon 20 insertion mutations confirmed by qualified local laboratories. Parts 2 and 3: EGFR/HER2 exon 20 insertion mutations confirmed by qualified local laboratories
- •Part 1: Has received all approved therapies for advanced or metastatic NSCLC or is ineligible. Part 2 and Part 3: Has received at least 1, but not more than 2, prior lines of approved treatment for advanced or metastatic NSCLC, 1 of which must be platinum-based chemotherapy unless contraindicated
- •Has documented tumor progression (based on radiological imaging)
- •Has new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen collected in the past 10 years available for genomic profiling
- •Has at least one measurable tumor lesion per RECIST v1.1
- •Is ≥18 years of age at the time of signing the ICF
- •Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
排除标准
- •Has a tumor that is known to harbor EGFR ex20ins p.H773_V774insH variant, or any EGFR kinase domain activating mutation concurrent with either a T790M and/or C797S resistance mutations
- •Has history (within ≤2 years before screening) of solid tumor or hematological malignancy that is histologically distinct from NSCLC
- •Has symptomatic brain or spinal metastases
- •Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE Grade ≤1, except for alopecia and peripheral neuropathy
- •Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., could compromise the participant's well-being) or would prevent, limit, or confound the protocol-specified assessments
研究组 & 干预措施
Part 1: Dose Escalation
干预措施: STX-721/PFL-721 (Escalated) (Drug)
Part 3: Dose Expansion
干预措施: STX-721/PFL-721 (RP2D) (Drug)
Part 2: RP2D Selection
干预措施: STX-721/PFL-721 (3 dose levels) (Drug)
结局指标
主要结局
Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
时间窗: 28 days
Part 2 RP2D Selection: Number of participants with confirmed objective response rate (ORR) defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1 per investigator assessment.
时间窗: 1 year
Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
时间窗: 28 days
Part 1 Dose Escalation (MTD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
时间窗: 28 days
Part 1 Dose Escalation (OBD): Dose Escalation - Number of participants who experience at least 1 DLT during the first 28 days of treatment
时间窗: 28 days
Part 2 RP2D Selection: C(max) of STX-721/PFL-721
时间窗: 1 year
Part 2 RP2D Selection: AUC(0-inf) of STX-721/PFL-721
时间窗: 1 year
Part 2 RP2D Selection: AUC(0-t) of STX-721/PFL-721
时间窗: 1 year
Part 2 RP2D Selection: AUC(0-τ) of STX-721/PFL-721
时间窗: 1 year
Part 2 RP2D Selection: Number of participants with confirmed objective response rate (ORR) defined as the percentage of participants with partial response (PR) or complete response (CR) based on RECIST v1.1 per investigator assessment.
时间窗: 1 year
Part 3 Dose Expansion: Number of participants with confirmed ORR defined as the percentage of participants with PR or CR based on RECIST v1.1 per investigator assessment.
时间窗: 1 year
次要结局
未报告次要终点