EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers

Neoplasms Clinical Trial

Official title:

Phase Ib/II, Open-Label Study of EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05176665
• Other study ID #: EMB01X201
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 21, 2021
• Est. completion date: August 31, 2024

Study information

• Verified date: June 2023
• Source: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Contact: Xiaodong Sun, MD
• Phone: +86-21-61043299
• Email: CT.info[@]epimab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 152
• Est. completion date: August 31, 2024
• Est. primary completion date: August 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Molecular Pre-screening Inclusion criteria (Phase II only)

1. cMET amplification in tumor sample; OR

2. cMET overexpression in tumor sample; OR

3. EGFR overexpression in tumor sample; OR

4. 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

1. Able to understand and willing to sign the Informed Consent Form (ICF).

2. 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:

1. 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.

2. Have measurable disease as defined by RESIST v 1.1.

3. Archival tumor tissue (formalin-fixed or paraffin-embedded, collected within 1 year) or a new biopsy collected in the molecular pre-screening visit.

4. Must have adequate organ function.

5. Regarding prior anti-tumor therapy:

1. 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-01.

2. Local radiotherapy or radiation therapy for bone metastases must have stopped 2 weeks before first dose of EMB-01. No therapeutic radiopharmaceuticals are taken within 8 weeks before first dose of EMB-01.

3. 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-01.

6. 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.

7. ECOG score =1.

Exclusion Criteria:

Molecular Pre-screening Exclusion Criteria

Subject who meets any of the following criteria can't be proceeded to clinical screening:

1. Patients who are unwilling to sign the molecular pre-screening ICF.

2. Patients for whom the results of central laboratory testing do not meet the molecular pre-screening inclusion criteria.

3. 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

1. Life expectancy < 3 months.

2. 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.

3. Pregnant or nursing females.

4. Patients who have had major surgery within the 28 days from the screening. Surgical wounds must be completely healed.

5. 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.

Related Conditions & MeSH terms

• Carcinoid Tumor
• Gastrointestinal Neoplasms
• Metastatic Gastrointestinal Carcinoid Tumor
• Neoplasm Metastasis
• Neoplasms

Intervention

Drug:
• EMB-01
EMB-01 at the RP2D of 1600 mg will be administered as an IV infusion once weekly (QW) throughout the study. One cycle is defined as 4 weeks (4 doses). All patients will be premedicated with a histamine-1 (H1) receptor antagonist diphenhydramine (25 or 50 mg) intravenously 30-60 minutes prior to dosing in the first two cycles. Premedication for subsequent treatment cycles will depend on whether the patient develops infusion-related reactions (IRR), at the discretion of the investigator.

Locations

Country	Name	City	State
China	Beijing cancer Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha
China	West China Hospital, Sichuan University	Chengdu
China	Nanfang Hospital	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Shandong Cancer Hospital	Jinan
China	Gansu Provincial Hospital	Lanzhou
China	The Affiliated hospital of Qingdao University	Qingdao
China	Fudan University Shanghai Cancer Center	Shanghai
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai EpimAb Biotherapeutics Co., Ltd.	Labcorp Corporation of America Holdings, Inc

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0	Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0	Phase 1b, screening up to follow-up (30 days after the last dose)
Primary	Best Overall Response (BOR) as assessed by RECIST v1.1	Best Overall Response (BOR) as assessed by RECIST v1.1	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
Primary	Objective Response Rate (ORR) as assessed by RECIST v1.1	Objective Response Rate (ORR) as assessed by RECIST v1.1	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
Primary	Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1	Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1	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
Primary	Disease Control Rate (DCR) as assess by RECIST v1.1	Disease Control Rate (DCR) as assess by RECIST v1.1	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
Primary	Progression-Free Survival (PFS) as assess by RECIST v1.1	Progression-Free Survival (PFS) as assess by RECIST v1.1	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
Primary	Maximum serum concentration (Cmax) of EMB-01	Maximum serum concentration (Cmax) of EMB-01	Phase Ib only, up to 3 months after first study drug administration
Primary	Trough serum concentration (Ctrough) of EMB-01	Trough serum concentration (Ctrough) of EMB-01	Phase Ib only, predose, through treatment completion, an average of 1 year
Primary	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 (pre-dose) to the time of the dosing interval (AUC0-t)	Phase Ib only, up to 3 months after first study drug administration
Primary	Area under the concentration-time curve from time 0 to infinity (AUC0-inf)	Area under the concentration-time curve from time 0 to infinity (AUC0-inf)	Phase Ib only, up to 3 months after first study drug administration
Primary	Elimination half-life (T1/2)	Elimination half-life (T1/2)	Phase Ib only, up to 3 months after first study drug administration
Primary	Systemic clearance (CL)	Systemic clearance (CL)	Phase Ib only, up to 3 months after first study drug administration
Primary	Apparent volume of distribution at steady-state (Vss)	Apparent volume of distribution at steady-state (Vss)	Phase Ib only, up to 3 months after first study drug administration
Primary	Accumulation Ratio (AR) after multiple dosing	Accumulation Ratio (AR) after multiple dosing	Phase Ib only, up to 3 months after first study drug administration
Primary	Incidence of positive ADA	Incidence of positive ADA	Phase Ib only, up to the 30-day safety follow-up visit after EOT
Primary	Clinical benefit rate(CBR) as assess by RECIST v1.1	Clinical benefit rate(CBR) as assess by RECIST v1.1	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
Secondary	Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0	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)
Secondary	Maximum serum concentration (Cmax) of EMB-01	Maximum serum concentration (Cmax) of EMB-01	Phase II, up to 3 months after first study drug administration
Secondary	Trough serum concentration (Ctrough) of EMB-01	Trough serum concentration (Ctrough) of EMB-01	Phase II, predose, through treatment completion, an average of 1 year
Secondary	Incidence of positive ADA	Incidence of positive ADA	Phase II , up to the 30-day safety follow-up visit after EOT
Secondary	Best Overall Response (BOR) as assessed by RECIST v1.1	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
Secondary	Objective Response Rate (ORR) as assessed by RECIST v1.1	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
Secondary	Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1	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
Secondary	Disease Control Rate (DCR) as assess by RECIST v1.1	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
Secondary	Progression-Free Survival (PFS) as assess by RECIST v1.1	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
Secondary	Clinical benefit rate(CBR) as assess by RECIST v1.1	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