A Phase III, Randomized, Open-Label, Multicenter Study to Evaluate GFH375 Versus Docetaxel in Participants With Locally Advanced and Unresectable or Metastatic Non-Small Cell Lung Cancer With KRAS G12D Mutation Failed Prior Standard Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Objective Response Rate(ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR)
研究概览
简要总结
The purpose of this study is to compare the effectiveness, safety and tolerability of GFH375 versus docetaxel in participants with KRAS G12D-mutant non-small cell lung cancer (NSCLC).
GFH375 is an oral, highly selective, non-covalent small-molecule inhibitor targeting the KRAS G12D mutation. Preclinical studies showed GFH375 strongly blocks KRAS-driven signaling and cancer cell growth, and demonstrated anti-tumor activity in NSCLC animal models. Docetaxel is a chemotherapy drug for locally advanced or metastatic NSCLC.
This is an open-label, randomized controlled trial. Both participant and study doctor will know which study medication each participant receives.
After enrollment, participant will be randomly assigned to either the GFH375 group or docetaxel group by chance. Neither participant nor study doctor can pick your treatment group. You have a two-thirds chance to receive GFH375 and a one-third chance to receive docetaxel.
- GFH375 group: Take GFH375 tablets by mouth once daily as scheduled; each treatment cycle lasts 21 days.
- Docetaxel group: Receive docetaxel via intravenous infusion at 75 mg/m² once every 3 weeks.
Study treatment will continue until cancer gets worse, participant can't tolerate the study treatment, or other conditions make participant unable to keep receiving study treatment.
Some participants on docetaxel may be able to switch to GFH375 during the study if their cancer becomes worse. There will be safety checks at each visit, and the doctors will continue to check for medical problems and participant 's wellbeing throughout the study. Participants will continue to have scans of their tumor every 6 weeks for the first year, then every 9 weeks until their cancer becomes worse. After participant's cancer becomes worse, clinic staff will telephone participant every 3 mouths to check on their cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •1. Voluntary participation in the study and signed informed consent form (ICF).
- •2. Age ≥ 18 years at the time of signing the ICF; male or female.
- •3. Histologically or cytologically confirmed locally advanced unresectable or metastatic non small cell lung cancer (NSCLC).
- •4. Participants must provide adequate and qualified tumor tissue slides samples or agree to undergo tumor biopsy to obtain tissue samples for central laboratory confirmation of KRAS G12D mutation.
- •5. Disease progression or intolerance to toxicity after at least one prior line of platinum based chemotherapy and anti PD 1/PD L1 antibody therapy.
- •6. At least one measurable target lesion according to RECIST version 1.
- •7. Investigator assessed life expectancy ≥ 12 weeks.
- •8. Adequate organ function.
- •9. Ability to communicate well, comply with scheduled follow up visits, and adhere to protocol requirements.
排除标准
- •1. Presence of other driver gene mutations in NSCLC, or concurrent other KRAS or RAS mutations.
- •2. Other malignancy that has progressed or required treatment within 3 years prior to randomization.
- •3. Leptomeningeal metastasis, or symptomatic or progressive central nervous system (CNS) metastasis.
- •4. Existing or potential severe bone injury due to bone metastasis, or uncontrolled pain related to bone metastasis.
- •5. Prior treatment with KRAS G12D targeted therapy or pan RAS/KRAS targeted therapy.
- •6. Prior treatment with docetaxel as part of systemic therapy.
- •7. Radiotherapy within 4 weeks prior to randomization, or other local anti tumor therapy within 4 weeks prior to randomization.
- •8. Other anti tumor therapy within 28 days or 5 half lives prior to randomization, or cell therapy within 3 months prior to randomization.
- •9. Clinically significant severe cardiovascular disease.
- •10. Stroke or other severe cerebrovascular disease within 6 months prior to randomization.
- •11. Major acute or chronic infectious disease.
- •12. Other poorly controlled systemic diseases.
- •13. Severe psychiatric or psychological disorder, or history of drug abuse, or severe alcohol abuse.
- •14. Pregnancy or breastfeeding.
- •15. Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.
研究组 & 干预措施
GFH375 group
Participants will take GFH375 orally once daily of every 21-day cycle.
干预措施: GFH375 (Drug)
Docetaxel group
Participants will receive docetaxel on day 1 of every 21-day cycle.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Objective Response Rate(ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR)
时间窗: From the first dose until the date of first documented CR or PR, assessed up to 24 months
ORR is the proportion of participants whose best response is either complete response (CR) or partial response (PR) per RECIST v1.1 assessed by BICR.
Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. as assessed by blinded independent central review (BICR)
时间窗: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
PFS is defined as the time from the date of randomization until the date of documented radiographic disease progression per RECIST v1.1, as assessed by BICR or until death due to any cause, whichever comes first.
Overall Survival (OS)
时间窗: From the first dose until the date of death from any cause, whichever came first, assessed up to 36~48 months
OS is defined as the time from the date of randomization until the date of death from any cause.
次要结局
- Objective Response Rate (ORR) per RECIST v1.1, as assessed by the investigator(From the first dose until the date of first documented CR or PR,assessed up to 24 months.)
- PFS per RECIST v1.1. as assessed by the investigator(From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.)
- DCR per RECIST v 1.1 as assessed by the investigator and the BICR(From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.)
- DoR per RECIST v 1.1 as assessed by the investigator and the BICR(From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.)
- Time to deterioration in NSCLC symptoms evaluated via European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) items(From the first dose until 30 days after the last dose, assessed up to 24 months.)
- TTR per RECIST v 1.1 as assessed by the investigator and the BICR(From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.)
- Number of Participants with Adverse Events (AEs)(From the first dose until 30 days after the last dose, assessed up to 24 months.)
- Severity of Adverse Events(AEs)(From the first dose until 30 days after the last dose, assessed up to 24 months.)
- Incidence of AEs that result in treatment discontinuation, treatment interruption, or dose reduction.(From the first dose until 30 days after the last dose, assessed up to 24 months.)
- Severity of adverse events (AEs) leading to treatment discontinuation, treatment interruption, and dose reduction.(From the first dose until 30 days after the last dose, assessed up to 24 months.)
- Time to Worsening measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) items(From the first dose until 30 days after the last dose, assessed up to 24 months.)
- Change from baseline in EORTC QLQ-C30(From the first dose to week12.)
- Change from baseline in EORTC QLQ-LC13(From the first dose to week12.)
- Pharmacokinetics (PK) of GFH375: Trough concentration after multiple dosing(From the first dose to Cycle 6 Day 1(each cycle is 21 days).)
- PK of GFH375: Peak concentration after multiple dosing(From the first dose to Cycle 6 Day 1(each cycle is 21 days).)