A Phase 1b/II, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 Combined With IN10018 in Subjects With Locally Advanced or Metastatic Solid Tumors With KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 140
- 试验地点
- 10
- 主要终点
- Objective Response Rate (ORR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
研究概览
简要总结
This is a phase 1b/II, open-label study to evaluate the safety, tolerability, pharmacokinetics and antitumor activities of D-1553 in combination with IN10018 in subjects with locally advanced or metastatic solid tumor with KRAS G12C mutation.
详细描述
This study includes 2 phases: Phase Ib-Dose Escalation and Phase II-Dose Expansion. Phase Ib-Dose Escalation part will enroll at least 6 subjects to identify the safety and RP2D of D1553 in combination with IN10018 in KRAS G12C mutant solid tumors. Phase II-Dose Expansion part contains 3 cohorts with cohort A to enroll advanced colorectal cancer (CRC) with KRAS G12C mutation, cohort B to enroll advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation, and cohort C to enroll other advanced solid tumors with KRAS G12C mutation. Phase II study is to evaluate the safety and antitumor activities of D-1553 in combination with IN10018 in KRAS G12C mutant solid tumors. The sample size in each cohort is estimated per Simon's 2-stage design. In Cohort A, when Simon's 2-stage study achieved statistical hypothesis, an open-label, randomized study will be conducted for factorial analysis to evaluate the contribution of IN10018 in the combination regimen.
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
- •Men or women aged ≥ 18 years at the time of signing the informed consent form.
- •Subjects with pathologically confirmed locally advanced or metastatic solid tumors.
- •Confirmed positive KRAS G12C mutation in tumor tissue or other biospecimens (only for phase1b) containing cancer cells or DNA.
- •Tumor types in different phases and cohorts: 1) Phase 1b: subjects with locally advanced or metastatic solid tumors who have progressed on or failed in standard therapy, and no standard treatment is available. 2) Phase II Cohort A: subjects with locally advanced or metastatic CRC. 3) Phase II Cohort B: subjects with locally advanced or metastatic NSCLC. 4) Phase 2 Cohort C: subjects with other locally advanced or metastatic solid tumors.
- •Has measurable lesions at baseline according to RECIST 1.1 criteria.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate bone marrow, liver, renal, and coagulation function within 7 days prior to the first dose.
排除标准
- •Prior KRAS G12C inhibitors treatment.
- •Have known symptoms of spinal cord compression, instable or symptomatic central nervous system (CNS) metastases, and/or carcinomatous meningitis.
- •Have a history of stroke or other serious cerebrovascular diseases within 12 months prior to the first dose.
- •Have had interstitial lung disease or any active infection requiring systemic treatment within 14 days prior to the first dose.
- •Has a history of severe cardiovascular disease such as acute myocardial infarction, severe/unstable angina, QTc prolongation, or poorly controlled hypertension.
- •Haven't recovered from toxicity due to prior antitumor therapy
- •Pregnant or lactating women.
- •Malignant neoplasms other than study disease within 5 years prior to enrollment.
研究组 & 干预措施
Phase 1b-Dose Escalation Part
To evaluate the safety and Recommended Phase 2 dose (RP2D) of D-1553 in combination with IN10018 in previously-treated solid tumors.
干预措施: IN10018（Ifebemtinib） (Drug)
Phase 1b-Dose Escalation Part
To evaluate the safety and Recommended Phase 2 dose (RP2D) of D-1553 in combination with IN10018 in previously-treated solid tumors.
干预措施: D1553 (Drug)
Phase II Cohort A-previously-treated CRC with KRAS G12C mutation（Treatmnt Group）
To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in previously-treated CRCs with KRAS G12C mutation.
干预措施: D1553 (Drug)
Phase II Cohort A-previously-treated CRC with KRAS G12C mutation（Treatmnt Group）
To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in previously-treated CRCs with KRAS G12C mutation.
干预措施: IN10018（Ifebemtinib） (Drug)
Phase II Cohort A-previously-treated CRC with KRAS G12C mutation (Control Group)
To evaluate the safety and antitumor efficacy of D-1553 in previously-treated CRCs with KRAS G12C mutation.
干预措施: D1553 (Drug)
Phase II Cohort C-other previously-treated solid tumors with KRAS G12C mutation
To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in other solid tumors with KRAS G12C mutation
干预措施: IN10018（Ifebemtinib） (Drug)
Phase II Cohort B-treatment-naïve or previously-treated NSCLC with KRAS G12C mutation
To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in advanced NSCLCs with KRAS G12C mutation.
干预措施: IN10018（Ifebemtinib） (Drug)
Phase II Cohort C-other previously-treated solid tumors with KRAS G12C mutation
To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in other solid tumors with KRAS G12C mutation
干预措施: D1553 (Drug)
Phase II Cohort B-treatment-naïve or previously-treated NSCLC with KRAS G12C mutation
To evaluate the safety and antitumor efficacy of D-1553 in combination with IN10018 in advanced NSCLCs with KRAS G12C mutation.
干预措施: D1553 (Drug)
结局指标
主要结局
Objective Response Rate (ORR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
时间窗: Through study completion, approximately 3 years
Defined as the proportion of subjects with complete response (CR) or partial response (PR).
Recommended phase II dose (RP2D) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation
时间窗: Through study completion, approximately 3 years
Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation.
次要结局
- Progression-free Survival (PFS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation(Through study completion, approximately 3 years)
- Overall survival (OS) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation(Through study completion, approximately 3 years)
- Number of subjects with adverse event(Through study completion, approximately 3 years)
- PK:t1/2 of D-1553 and IN10018(Through study completion, approximately 3 years)
- Disease Control Rate (DCR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation(Through study completion, approximately 3 years)
- PK: Cmax of D-1553 and IN10018(Through study completion, approximately 3 years)
- PK: Cmin of D-1553 and IN10018(Through study completion, approximately 3 years)
- PK: AUC of D-1553 and IN10018(Through study completion, approximately 3 years)
- Duration of Response (DoR) of D1553 in combination with IN10018 in solid tumors with KRAS G12C mutation(Through study completion, approximately 3 years)
- PK:CL/F of D-1553 and IN10018(Through study completion, approximately 3 years)
- PK:Vd/F of D-1553 and IN10018(Through study completion, approximately 3 years)
- Plasma concentrations of D-1553 and IN10018 in solid tumors with KRAS G12C mutation(Through study completion, approximately 3 years)