An Open-label Phase II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of ABSK043 in Combination With Glecirasib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring a KRAS G12C Mutation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 86
- 试验地点
- 17
- 主要终点
- AESIs AESIs
研究概览
简要总结
This is a multicenter, open-label phase 2 study that will enroll KRASG12C mutated patients with locally advanced or metastatic NSCLC, receiving treatment (ABSK043 in combination with Glecirasib) in a 21-day combination cycle.
详细描述
The study consists of an escalation part and an expansion part. The escalation part will evaluate the safety, tolerability, preliminary efficacy, and PK profile of different doses of ABSK043 in combination with Glecirasib, and the combination regimen recommended for the expansion part. The expansion part will further evaluate the safety, PK profile, and anti-tumor efficacy of ABSK043 in combination with Glecirasib at the one or more recommended dose (s).
Up to 86 patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) are planned to be enrolled in the study.
- Escalation Part: up to 50 previously treated patients with KRASG12C mutation.
- Expansion Part: up to 36 treatment-naïve patients with KRASG12C mutation.
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
- •Prior to any protocol- specific procedures are performed, the patient should understand and voluntarily sign and date the written informed consent form.
- •Gender was not limited patients aged ≥18 years at the time of signing the informed consent.
- •Histologically or cytologically confirmed locally advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC).
- •For patients in the dose-escalation cohort (Part A) of the escalation part:
- •Patients must have experienced disease progression following at least one line of prior standard systemic therapy, but no more than two lines of systemic therapy.
- •For patients in the dose confirmation cohort (Part B) of the escalation part :
- •Prior treatment requirements for patients in cohort (Part B) are the same as those for patients in (Part A);
- •Documented or central laboratory test report confirmed that the tumor was PD-L1 expression positive (≥1%) .
- •For patients in the expansion cohort of the expansion part :
- •Patients who have not received prior systemic therapy for locally advanced or unresectable/metastatic disease;
- •Central laboratory test report confirmed that the tumor was PD-L1 expression positive (≥1%) .
- •Tumor tissue or blood test report confirmed KRASG12C mutation.
- •Patients must have at least one measurable lesion as defined by RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0~
- •Expected survival time of ≥3 months.
- •Patients must have adequate organ and bone marrow function.
排除标准
- •Histological or cytological evidence of small cell lung cancer or neuroendocrine carcinoma components.
- •Toxicities from prior antitumor therapy have not returned to baseline or stabilized.
- •Patients with active brain metastases.
- •The patient currently has active interstitial lung disease.
- •Patients currently have active autoimmune disease or a history of autoimmune disease that may be at risk for recurrence.
- •Any condition requiring systemic treatment with corticosteroids.
- •Uncontrolled or significant cardiovascular disease.
- •Has a known human immunodeficiency virus (HIV) infection that is not well controlled.
- •Any evidence of severe or uncontrolled diseases or other factors which in the Investigator's opinion makes it undesirable for the patients to participate in the study
研究组 & 干预措施
Experimental: ABSK043 in combination with Glecirasib
This is an open-label phase 2 study with an escalation part and an expansion part.
• Escalation Part: up to 50 previously treated patients with KRASG12C mutation. Does Escalation Cohort(Part A): up to 30previously treated patients with KRASG12C mutation.
Dose Confirmation Cohort(Part B): up to 20previously treated patients with KRASG12C mutation.
• Expansion Part: up to 36 treatment-naïve patients with KRASG12C mutation.
干预措施: ABSK043 in combination with Glecirasib (Drug)
结局指标
主要结局
AESIs AESIs
时间窗: From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of Glecirasib, whichever occurs first, up to 30 months.
Adverse events of special interest (AESIs)
Incidence of DLT
时间窗: At the end of Cycle 1 (each cycle is 21 days)
Dose-limiting toxicities
AEs
时间窗: From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of Glecirasib, whichever occurs first, up to 30 months.
Adverse events
ORR
时间窗: From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 50 months.
objective response rate
SAEs
时间窗: From the time the patient signs the informed consent form throughout the study and up to 90 days after the last dose of ABSK043 or 30 days after the last dose of Glecirasib, whichever occurs first, up to 30 months.
Serious adverse events (SAEs)
次要结局
- Cmax,ss(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- Cmin,ss(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- AUCtau,ss(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- AR(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- tmax(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- DOR DOR(From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 50 months.)
- PFS(From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 50 months.)
- DCR(From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 50 months.)
- TTP(From date of enrolment #Cycle1 Day1# until disease progression, assessed up to 50 months.)
- OS(From date of enrolment#Cycle1 Day1# until disease progression, death, loss to follow-up, withdrawal of consent, intolerable toxicity, investigator's decision to discontinue treatment, or end of study, whichever comes first, assessed up to 50 months.)
- Cmax(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months)
- AUC(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- t1/2 t1/2(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- Vz/F(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)
- CL/F(From the date of enrolment #Cycle1 Day1# to #Cycle7#, and for patients who discontinue treatment before cycle 7 (C7), PK sampling will be performed at the EOT visit and assessed up to 10 months.)