EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms; Neoplasm Metastasis; Metastatic Gastrointestinal Carcinoid Tumor
• Intervention / Treatment: Drug: EMB-01

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 152
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rong Wang, M.Sc; Phone Number: +86-21-61043299; Email: CT.info@epimab.com
• Study Contact Backup: Name: Di Hu, M.Sc; Phone Number: +862161043299; Email: CT.info@epimab.com

Study Locations

• China
  • Changsha, China
    • Recruiting
    • Hunan Cancer Hospital
    • Contact: Shanzhi Gu
  • Chengdu, China
    • Recruiting
    • West China Hospital, Sichuan University
    • Contact: Meng Qiu
  • Guangzhou, China
    • Recruiting
    • The Sixth Affiliated Hospital of Sun Yat-sen University
    • Contact: Yanhong Deng
  • Hangzhou, China
    • Recruiting
    • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Contact: Hongming Pan
  • Harbin, China
    • Recruiting
    • Harbin medical university cancer hospital
    • Contact: Yanqiao Zhang
  • Jinan, China
    • Recruiting
    • Shandong Cancer Hospital
    • Contact: Changzheng Li
  • Lanzhou, China
    • Recruiting
    • Gansu Provincial Hospital
    • Contact: Weisheng Zhang
  • Qingdao, China
    • Not yet recruiting
    • The Affiliated Hospital of Qingdao University
    • Contact: Zimin Liu
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhiyu Chen
  • Xi'an, China
    • Not yet recruiting
    • The First Affiliated Hospital of Xi'an Jiaotong University
    • Contact: Enxiao Li
  • Zhengzhou, China
    • Recruiting
    • First Affiliated Hospital of Zhengzhou University
    • Contact: Yanru Qin
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Lin Shen
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital
      • Contact: Yabing Guo
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Michael Lee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Molecular Pre-screening Inclusion criteria

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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).; Other Names: FIT-013a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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
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
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
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
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
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
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
Elimination half-life (T1/2)	Elimination half-life (T1/2)	Phase Ib only, up to 3 months after first study drug administration
Systemic clearance (CL)	Systemic clearance (CL)	Phase Ib only, up to 3 months after first study drug administration
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
Accumulation Ratio (AR) after multiple dosing	Accumulation Ratio (AR) after multiple dosing	Phase Ib only, up to 3 months after first study drug administration
Incidence of positive ADA	Incidence of positive ADA	Phase Ib only, up to the 30-day safety follow-up visit after EOT
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
Incidence of positive ADA	Incidence of positive ADA	Phase II , up to the 30-day safety follow-up visit after EOT
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Collaborators: Labcorp Corporation of America Holdings, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: December 31, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Neoplasm Metastasis; Epidermal Growth Factor Receptor (EGFR); Human Bispecific antibody; c-Mesenchymal-Epithelial Transition (cMet); Neoplasms， Neoplasm Metastasis; EMB-01，Tyrosine Kinase Inhibitor (TKI) Resistant
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gastrointestinal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neuroendocrine Tumors; Neoplasms; Neoplasm Metastasis; Gastrointestinal Neoplasms; Carcinoid Tumor
• Other Study ID Numbers: EMB01X201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No