A Phase 3 Multicenter, Randomized, Controlled, and Open-Label Study of IN10018 in Combination With D-1553 Versus Standard Therapy for the Treatment of First Line Locally-advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 11
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a multicenter, randomized, open-label, phase III clinical study, to evaluate the efficacy and safety of IN10018 in combination with D-1553 as compared to anti-PD-1 monoclonal antibody (mAb) in combination with platinum and pemetrexed as the first-line treatment for the locally advanced or metastatic KRASG12C mutation-positive non-squamous non-small cell lung cancer (NSCLC).
详细描述
Preclinical studies indicate that IN10018 synergizes with D-1553 to enhance antitumor activity and delay resistance through multiple mechanisms, including suppression of FAK-YAP signaling pathway activation, reduction of tumor stromal fibrosis, and induction of immunogenic cell death (ICD). IN10018-602/D1553-106 is an ongoing Phase Ib/II clinical study evaluating the synergistic antitumor activity and safety of IN10018 combined with D-1553 in patients with KRAS G12C-mutant solid tumors. Preliminary results have demonstrated notable antitumor activity and a favorable safety and tolerability profile in patients with advanced KRAS G12C-mutant NSCLC and metastatic colorectal cancer. Based on the available clinical data, the sponsor plans to initiate a Phase III study in previously untreated patients with advanced KRAS G12C-mutant NSCLC to further evaluate the efficacy and safety of IN10018 in combination with D-1553 compared with first-line standard treatment.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to provide informed consent and comply with study requirements
- •Has histologically confirmed locally advanced (Stage IIIB/C) or metastatic (Stage IV) non-squamous NSCLC
- •Aged 18-80 years at the time of consent
- •Has KRAS G12C mutation confirmed by central laboratory
- •Has not received prior systemic therapy for advanced or metastatic NSCLC
- •Has at least one measurable lesion per RECIST v1.1
- •ECOG performance status of 0-1
- •Has adequate organ function
- •Life expectancy ≥3 months in the opinion of the Investigator
- •Male and female subjects of reproductive potential must agree to use effective contraception during and for 6 months after treatment
排除标准
- •Has other histological subtypes of NSCLC (e.g., small cell or neuroendocrine)
- •Has active or untreated CNS metastases or carcinomatous meningitis
- •Prior treatment with KRAS G12C inhibitors, FAK inhibitors, or immune checkpoint inhibitors
- •Has another known driver mutation with approved targeted therapy (e.g., EGFR, ALK, ROS1)
- •Has uncontrolled cardiovascular disease, active severe infection, interstitial lung disease, or autoimmune disease requiring systemic therapy
- •Has history of another malignancy within 5 years, except those curatively treated and considered low risk (e.g., basal cell carcinoma, cervical carcinoma in situ)
- •Has gastrointestinal conditions that may interfere with absorption of oral drugs (if applicable)
- •Has known active hepatitis B, hepatitis C, or HIV infection
- •Has received a live vaccine within 30 days before first dose of study drug
- •Pregnant or breastfeeding women
- •Has psychiatric or substance abuse disorders that would interfere with study compliance
- •Is participating in another interventional clinical study
- •Any condition that, in the opinion of the Investigator, would interfere with participation or study results
研究组 & 干预措施
IN10018 plus D-1553
Subjects receive IN10018 100mg orally once daily (QD) and D-1553 600mg orally twice daily (BID) on Days 1-21 of each 21-day cycle, until disease progression or unacceptable toxicity.
干预措施: IN10018 in combination with D-1553 (Drug)
Tislelizumab plus Platinum and Pemetrexed
Subjects receive Tislelizumab 200mg intravenously (IV) once every 3 weeks (Q3W) until disease progression, plus Carboplatin (AUC = 5 mg/mL/min, Q3W, IV) or Cisplatin (75 mg/m², Q3W, IV) for up to 4 cycles, in combination with Pemetrexed (500 mg/m², Q3W, IV) until disease progression.
干预措施: anti-PD-1 monoclonal antibody in combination with platinum and pemetrexed (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: up to 36 months
Defined as time from randomization until disease progression or death from any cause, whichever occurs first assessed per RECIST v1.1 by blinded independent central review (BICR).
次要结局
- Objective Response Rate (ORR)(up to 36 months)
- Overall Survival (OS)(up to 60 months)
- Disease Control Rate (DCR)(Up to 36 months)
- Duration of Response (DoR)(up to 36 months)
- PFS(up to 36 months)
- ORR(up to 36 months)
- DCR(up to 36 months)
- DOR(Up to 36 months)
- Number of subjects with adverse event(up to 36 months)