A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-21822 Monotherapy and Combination Therapy in Adult Patients with Advanced Solid Tumors Harboring KRAS G12C Mutation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 111
- 试验地点
- 4
- 主要终点
- Dose Escalation Phase (Phase 1): Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period; Incidence, nature, and severity of TEAEs, TRAEs, and death per NCI CTCAE v5
研究概览
简要总结
Dose Escalation Phase (Phase 1):
- To evaluate the overall safety and tolerability of JAB-21822 monotherapy
- To determine the MTD and a RP2D of JAB-21822 monotherapy administered QD in participants with relapsed or refractory solid tumors with KRAS G12C mutation
Dose Expansion Phase (Phase 2):
- To further evaluate preliminary antitumor activity, ORR, and DOR of JAB-21822 monotherapy at the RP2D in participants with relapsed and refractory NSCLC and other solid tumors with KRAS G12C mutation, and in combination with cetuximab in mCRC with KRAS G12C mutation
研究设计
- 研究类型
- Interventional
- 分配方式
- Non-randomized
- 主要目的
- Jab-21822 Activity In Adult Patients With Advanced Solid Tumors Harboring Kras G12c Mutation
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Participants must have at least 1 measurable lesion as defined by RECIST v1.
- •Participants must be able to provide an archived tumor sample
- •Participant has histologically or cytologically confirmed solid tumors with KRAS G12C mutation
- •Must have received at least 1 prior standard therapy
- •Participants must be able to swallow and retain orally administered medication.
- •Participants must have laboratory data that meet the following criteria: a. Absolute neutrophil count ≥1.5 × 109/L. b. Platelet count ≥100 × 109/L. c. Hemoglobin ≥9 g/dL. d. Albumin ≥3.0 g/dL. e. Total bilirubin ≤1.5 × ULN (with Gilbert’s syndrome, ≤2.0 × ULN). f. AST and ALT ≤1.5 × ULN (with presence of liver metastases, ≤3 × ULN). g. PT and PTT <1.5 × ULN and INR <1.5 if the participant is not on anticoagulants, or INR <3 after dose titration has been completed if the participant is on anticoagulants. h. Kidney function is normal with a CrCl ≥ 60 mL/min (measured using Cockcroft-Gault equation; see Appendix 13.4). i. TSH within normal range at baseline. Additional thyroid function testing (such as free T4, T3, etc.) can be performed at the investigator’s discretion.
排除标准
- •Active infection requiring systemic treatment at the start of treatment in this trial. A washout period of 7 days after the last dose of antibiotics, antivirals, or antifungals prior to first dose of study drug is required.
- •Participant has brain or spinal metastases, except if treated by surgery, surgery plus radiotherapy or radiotherapy alone, with no evidence of radiographic progression or hemorrhage for at least 28 days
- •Has active HBV or HCV
- •History of any severe and/or uncontrolled medical conditions
- •LVEF ≤50% assessed by ECHO or QTcF
- •QT interval >470 msec
- •Participants experiencing unresolved Grade >1 toxicity before the start of treatment with the study drug
结局指标
主要结局
Dose Escalation Phase (Phase 1): Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period; Incidence, nature, and severity of TEAEs, TRAEs, and death per NCI CTCAE v5
Dose Escalation Phase (Phase 1): Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period; Incidence, nature, and severity of TEAEs, TRAEs, and death per NCI CTCAE v5
Dose Escalation Phase (Phase 1): Treatment-emergent changes in clinical laboratory measurements, ECG findings, vital signs, ECOG performance status, and physical examination findings
Dose Escalation Phase (Phase 1): Treatment-emergent changes in clinical laboratory measurements, ECG findings, vital signs, ECOG performance status, and physical examination findings
Dose Escalation Phase (Phase 1): Number and proportion of participants who experience at least 1 DLT during the first 21 days of treatment
Dose Escalation Phase (Phase 1): Number and proportion of participants who experience at least 1 DLT during the first 21 days of treatment
Dose Expansion Phase (Phase 2): ORR defined as the percentage of participants with PR or CR based on RECIST v1.1
Dose Expansion Phase (Phase 2): ORR defined as the percentage of participants with PR or CR based on RECIST v1.1
Dose Expansion Phase (Phase 2): DOR
Dose Expansion Phase (Phase 2): DOR
次要结局
- Dose Expansion Phase (Phase 2): PFS and TTR
- Dose Expansion Phase (Phase 2): OS
- Dose Expansion Phase (Phase 2): DCR
- Dose Escalation Phase (Phase 1): ORR defined as the percentage of participants with PR or CR based on RECIST v1.1
- Dose Escalation Phase (Phase 1): DCR, TTR, DOR, and PFS
- Dose Escalation Phase (Phase 1): PK parameters of JAB-21822 including, but not limited to, Cmax, tmax, Ctrough, AUC0-τ, AUC0-t, AUC0 inf, t½, CL/F, Vz/F, Rac Cmax, and Rac AUC
- Dose Expansion Phase (Phase 2): Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period; Incidence, nature, and severity of TEAEs, TRAEs, and death per NCI CTCAE v5
- Dose Expansion Phase (Phase 2): Treatment-emergent changes in clinical laboratory measurements, ECG findings, vital signs, ECOG performance status, and physical examination findings
- Dose Expansion Phase (Phase 2): PK parameters of JAB-21822 and potential factors (covariates) that impact the PK parameters
研究者
Zheng Xu
Scientific
Jacobio Pharmaceuticals Co. Ltd.