A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of ABSK043 Combined With Osimertinib in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 72
- 试验地点
- 7
- 主要终点
- - Incidence of dose-limiting toxicity (DLT)
研究概览
简要总结
This is a phase 2, open-Label study to evaluate the efficacy and safety of ABSK043 Combined with Osimertinib in participants with EGFR-Mutated locally advanced or metastatic Non-Small Cell Lung Cancer
详细描述
This is an open-label study with an escalation part and an expansion part. The dose escalation part will evaluate the safety, tolerability of ABSK043 in combination with Osimertinib in previously treated participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC. The expansion part will evaluate the efficacy of ABSK043 in combination with Osimertinib as first-line treatment for participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC at the one or more recommended dose(s). The safety, tolerability, and PK profile of ABSK043 in combination with Osimertinib will also be further evaluated.
Escalation Part:
The escalation part includes dose escalation cohorts and backfill cohort(s), enrolling a sufficient number with previously treated participants with EGFR-mutated and PD-L1 positive locally advanced or metastatic NSCLC.
Expansion Part:
The expansion part will enroll a sufficient number with treatment-naïve participants with locally advanced or metastatic NSCLC harboring the EGFR mutation and PD-L1 positive expression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Aged 18 or above, male or female.
- •Participants must understand and voluntarily participate in this study and must have been provided informed consent for study participation.
- •NSNLC confirmed by tissue or cytological pathology. NSCLC with a mixed histology is eligible, if adenocarcinoma is the predominant histology.
- •Diagnosed locally advanced or metastatic NSCLC
- •Different requirements for specific cohort:
- •Dose escalation and backfill cohorts:
- •Participants with disease in the adjuvant setting, post chemoradiotherapy setting, locally advanced stage or metastatic stage, who have received at least one prior line of third-generation EGFR-TKI-based monotherapy or combination therapy and experienced disease progression.
- •Participants must have received ≥2 prior lines of frontline systemic therapy.
- •Documented or central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
- •Documented genetic testing report confirms the presence of EGFR alteration(s) in tumor or plasma.
- •Expansion cohort(s):
- •Participants must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting for locally advanced or metastatic disease.
- •Central laboratory test report confirms that the tumor is PD-L1 expression positive (TPS/TC≥1%).
- •Documented genetic testing reports confirm the presence of EGFR
- •Presence of at least one measurable tumor lesion
- •ECOG score 0-1 at screening.
- •The expected life expectancy after the first dose is >12 weeks.
排除标准
- •1. Histological or cytological examinations suggest that NSCLC squamous cells is the predominant histology, or contains small cell lung cancer, neuroendocrine carcinoma, etc.
- •2. Has a history of interstitial lung disease (ILD)/pneumonitis or active ILD
- •Spinal cord compression and unstable brain metastases. 4.Any unresolved toxicities from prior systemic therapy greater than CTCAE v6.0 Grade 1 at the time of starting study treatment.
- •5. Participants with obvious and unstable pleural effusion, peritoneal effusion or pericardial effusion .
- •6. Has a history of other malignant tumors, or currently have other malignant tumors.
- •7. Participants with known HIV infection.
结局指标
主要结局
- Incidence of dose-limiting toxicity (DLT)
时间窗: At the end of Cycle 1 (each cycle is 21 days)
Escalation Part
Adverse events(AEs)
时间窗: From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months.
Escalation Part
Serious adverse events (SAEs)
时间窗: From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months.
Escalation Part
Adverse events of special interest (AESIs)
时间窗: From the time the patient signs the informed consent form throughout the study and up to 30 days (± 7 days) after the last dose of ABSK043 or Osimertinib, up to 30 months.
Escalation Part
Progression-free survival at 12 month
时间窗: From the time patients receive the first dose of study drug to 12 months，assessed up to 5 years.
Expansion Part
次要结局
- Maximum observed concentration（Cmax）(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Area under the concentration-time curve area under the concentration-time curve area under the concentration-time curve (AUC)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Elimination half-life(t1/2)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Apparent volume of distribution(Vz/F)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Apparent oral clearance(CL/F)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Maximum observed concentration after multiple doses(Cmax,ss)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Minimum observed concentration after multiple doses(Cmin,ss)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Area under the concentration-time curve after multiple doses(AUCtau,ss)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Accumulation ratio(AR)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Time to maximum observed concentration(tmax)(From the date of enrolment #Cycle1 Day1 to EOT visit and assessed up to 10 months.)
- Progression-Free Survival (PFS)(From treatment start up to 5 years)
- Objective response rate (ORR)(From treatment start up to 5 years)
- Duration of response (DOR)(From treatment start up to 5 years)
- Disease control rate (DCR)(From treatment start up to 5 years)
- Time to progression (TTP)(From treatment start up to 5 years)
- Overall survival (OS)(From treatment start up to 7 years)