EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers

NCT05176665 | Recruiting Phase 1 FDA Drug

• 1 other identifier: EMB01X201
• Study Type: interventional
• Target: 152
• Locations: 2 countries
• Sites: 14

Brief 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.

Conditions

Neoplasms; Neoplasm Metastasis; Metastatic Gastrointestinal Carcinoid Tumor

Keywords

Human Bispecific antibody; Epidermal Growth Factor Receptor (EGFR); c-Mesenchymal-Epithelial Transition (cMet); Neoplasms， Neoplasm Metastasis; Neoplasm Metastasis; EMB-01，Tyrosine Kinase Inhibitor (TKI) Resistant

Outcome Measures

Primary Outcomes (16)

• 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 Outcomes (10)

• 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

  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

• 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

Study Arms (1)

Phase Ib and Phase II

EXPERIMENTAL

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

Interventions

EMB-01 DRUG

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).

Also known as: FIT-013a

Phase Ib and Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 1.1.
• 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-01.
• 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.
• 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.

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• Shanghai EpimAb Biotherapeutics Co., Ltd.: lead
• Labcorp Corporation of America Holdings, Inc: collaborator

Study Sites (14)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Beijing cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

RECRUITING

Hunan Cancer Hospital

Changsha, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, China

RECRUITING

The Sixth Affiliated Hospital of Sun Yat-Sen University

Guangzhou, China

RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, China

RECRUITING

Shandong Cancer Hospital

Jinan, China

RECRUITING

Gansu Provincial Hospital

Lanzhou, China

RECRUITING

The Affiliated hospital of Qingdao University

Qingdao, China

NOT YET RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, China

NOT YET RECRUITING

First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

RECRUITING

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Rong Wang, M.Sc

CONTACT

+86-21-61043299; CT.info@epimab.com

Di Hu, M.Sc

CONTACT

+862161043299; CT.info@epimab.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: January 4, 2022
• Study Start: October 21, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 26, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (13); US (1)