Phase Ib/II, Open-Label Study of EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 152
- 试验地点
- 14
- 主要终点
- Objective Response Rate (ORR) as assessed by RECIST v1.1
研究概览
简要总结
This study is to evaluate the safety and antitumor activity of EMB-01 in advanced/metastatic gastrointestinal cancers, including gastric cancer, hepatocellular cancer, cholangiocarcinoma and colorectal cancer.
详细描述
This is an open-label, Phase Ib/II, multi-stage study of EMB-01 in patients with advanced gastrointestinal tumors including gastric cancer, hepatocellular cancer, cholangiocarcinoma cancer and colorectal cancer, who have EGFR/cMET gene alterations or protein over expression and progressed on available standard therapies and for whom no standard therapy exists that would confer clinical benefit. All patients will be prescreened for cMET and EGFR genetic alterations and protein expression. Only those who met the molecular pre-screening criteria will proceed to clinical screening to determine the eligibility. The study will consist of Phase Ib part and Phase II part, both phases will consist of a molecular prescreening period, screening period, treatment period, safety follow-up period, and disease progression follow-up.
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
- •Molecular Pre-screening Inclusion criteria
- •cMET amplification in tumor sample; OR
- •cMET overexpression in tumor sample; OR
- •EGFR overexpression in tumor sample; OR
- •Other EGFR or cMET gene alteration in blood sample (circulating tumor DNA, ctDNA).
- •In Phase II, CRC patients must provide blood sample for NGS test, but may not provide tumor samples at prescreening visit. CRC patients don't need to meet the above criteria of EGFR/cMET amplification, overexpression or gene aberration.
- •Screening Inclusion Criteria
- •Able to understand and willing to sign the Informed Consent Form (ICF).
- •Histologically/cytologically confirmed advanced/metastatic gastric cancer, HCC, BTC, and colorectal cancer with measurable disease (RECIST V1.1). To be eligible, patients must meet following criteria:
- •Have failed all standard of care therapies known to confer clinical benefit. Patients who is not tolerable on standard of care therapies, or no standard of care therapies available, or refused standard of care therapies are eligible.
- •Have measurable disease as defined by RESIST v 1.
- •Archival tumor tissue (formalin-fixed or paraffin-embedded, collected within 1 year) or a new biopsy collected in the molecular pre-screening visit.
- •Must have adequate organ function.
- •Regarding prior anti-tumor therapy:
- •Patients who have received any anticancer drugs approved or investigational, including chemotherapy, immune therapy, hormonal therapy (Exceptions: hormone-replacement therapy, testosterone or oral contraceptives), biologic therapy, must have stopped treatment at least 4 weeks or within 5 half -lives whichever shorter before first dose of EMB-
- •Local radiotherapy or radiation therapy for bone metastases must have stopped 2 weeks before first dose of EMB-
- •No therapeutic radiopharmaceuticals are taken within 8 weeks before first dose of EMB-
- •Patients who have received prior targeted therapies must have stopped treatment for at least 4 weeks or within 5 half-lives, whichever is shorter before first dose of EMB-
- •Female patient with fertility or male patient whose partner has fertility should use one or more contraceptive methods for contraception starting from screening period and continue throughout the study treatment and for 3 months.
- •ECOG score ≤1.
排除标准
- •Molecular Pre-screening Exclusion Criteria
- •Subject who meets any of the following criteria can't be proceeded to clinical screening:
- •Patients who are unwilling to sign the molecular pre-screening ICF.
- •Patients for whom the results of central laboratory testing do not meet the molecular pre-screening inclusion criteria.
- •Patients with a documented gene alteration including but not limited to HER2, KRAS, NRAS, BRAF, NTRK, ALK, RET, ROS1, and FGFR, etc. that is known to confer resistance to EGFR and/or cMET inhibitors.* * In Phase II, CRC patients with activated KRAS, NRAS or BRAF mutation should be excluded, but patients with other gene alterations do not need to be excluded.
- •Screening Exclusion Criteria
- •Life expectancy < 3 months.
- •Patients with primary central nervous system (CNS) malignancy or symptomatic CNS (leptomeningeal or brain) metastases are not allowed. Patients with asymptomatic CNS metastases are eligible.
- •Pregnant or nursing females.
- •Patients who have had major surgery within the 28 days from the screening. Surgical wounds must be completely healed.
- •Any other serious underlying medical (e.g. uncontrolled diabetes mellitus, active uncontrolled infection, active gastric ulcer, uncontrolled seizures, cerebrovascular incidents, gastrointestinal bleeding, severe signs and symptoms of coagulation and clotting disorders, cardiac conditions), psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
研究组 & 干预措施
Phase Ib and Phase II
The study will consist of Phase Ib and Phase II. The study is planning to recruit approximately 152 patients in total for advanced/metastatic GI cancers, which include 24 patients in Phase Ib and up to approximately 128 patients in Phase II. For GC, HCC, and BTC groups, up to approximately 24 patients may be enrolled in Phase Ib and Phase II. For CRC group, up to approximately 80 patients may be enrolled in Phase Ib and Phase II with up to 40 patients in each subgroup.
干预措施: EMB-01 (Drug)
结局指标
主要结局
Objective Response Rate (ORR) as assessed by RECIST v1.1
时间窗: Phase II, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Objective Response Rate (ORR) as assessed by RECIST v1.1
Disease Control Rate (DCR) as assess by RECIST v1.1
时间窗: Phase II, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Disease Control Rate (DCR) as assess by RECIST v1.1
Trough serum concentration (Ctrough) of EMB-01
时间窗: Phase Ib only, predose, through treatment completion, an average of 1 year
Trough serum concentration (Ctrough) of EMB-01
Best Overall Response (BOR) as assessed by RECIST v1.1
时间窗: Phase II, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Best Overall Response (BOR) as assessed by RECIST v1.1
Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
时间窗: Phase 1b, screening up to follow-up (30 days after the last dose)
Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1
时间窗: Phase II, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1
Maximum serum concentration (Cmax) of EMB-01
时间窗: Phase Ib only, up to 3 months after first study drug administration
Maximum serum concentration (Cmax) of EMB-01
Apparent volume of distribution at steady-state (Vss)
时间窗: Phase Ib only, up to 3 months after first study drug administration
Apparent volume of distribution at steady-state (Vss)
Systemic clearance (CL)
时间窗: Phase Ib only, up to 3 months after first study drug administration
Systemic clearance (CL)
Progression-Free Survival (PFS) as assess by RECIST v1.1
时间窗: Phase II, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Progression-Free Survival (PFS) as assess by RECIST v1.1
Area under the concentration-time curve from time 0 (pre-dose) to the time of the dosing interval (AUC0-t)
时间窗: Phase Ib only, up to 3 months after first study drug administration
Area under the concentration-time curve from time 0 (pre-dose) to the time of the dosing interval (AUC0-t)
Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
时间窗: Phase Ib only, up to 3 months after first study drug administration
Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Incidence of positive ADA
时间窗: Phase Ib only, up to the 30-day safety follow-up visit after EOT
Incidence of positive ADA
Elimination half-life (T1/2)
时间窗: Phase Ib only, up to 3 months after first study drug administration
Elimination half-life (T1/2)
Accumulation Ratio (AR) after multiple dosing
时间窗: Phase Ib only, up to 3 months after first study drug administration
Accumulation Ratio (AR) after multiple dosing
Clinical benefit rate(CBR) as assess by RECIST v1.1
时间窗: Phase II, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Clinical benefit rate(CBR) as assess by RECIST v1.1
次要结局
- Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0(Phase II, screening up to follow-up (30 days after the last dose))
- Best Overall Response (BOR) as assessed by RECIST v1.1(Phase Ib, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months)
- Maximum serum concentration (Cmax) of EMB-01(Phase II, up to 3 months after first study drug administration)
- Trough serum concentration (Ctrough) of EMB-01(Phase II, predose, through treatment completion, an average of 1 year)
- Incidence of positive ADA(Phase II , up to the 30-day safety follow-up visit after EOT)
- Progression-Free Survival (PFS) as assess by RECIST v1.1(Phase Ib, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months)
- Disease Control Rate (DCR) as assess by RECIST v1.1(Phase Ib, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months)
- Clinical benefit rate(CBR) as assess by RECIST v1.1(Phase Ib, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months)
- Objective Response Rate (ORR) as assessed by RECIST v1.1(Phase Ib, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months)
- Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1(Phase Ib, from the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months)