Clinical trial NCT05176665: EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers
Official title: Phase Ib/II, Open-Label Study of EMB-01 in Patients With Advanced/Metastatic Gastrointestinal Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Labcorp Corporation of America Holdings, Inc
First posted: 2022-01-04
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
timeFrame: Phase 1b, screening up to follow-up (30 days after the last dose)
measure: Best Overall Response (BOR) as assessed by RECIST v1.1
timeFrame: 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
measure: Objective Response Rate (ORR) as assessed by RECIST v1.1
timeFrame: 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
measure: Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1
timeFrame: 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
measure: Disease Control Rate (DCR) as assess by RECIST v1.1
timeFrame: 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
measure: Progression-Free Survival (PFS) as assess by RECIST v1.1
timeFrame: 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
measure: Maximum serum concentration (Cmax) of EMB-01
timeFrame: Phase Ib only, up to 3 months after first study drug administration
measure: Trough serum concentration (Ctrough) of EMB-01
timeFrame: Phase Ib only, predose, through treatment completion, an average of 1 year
measure: Area under the concentration-time curve from time 0 (pre-dose) to the time of the dosing interval (AUC0-t)
timeFrame: Phase Ib only, up to 3 months after first study drug administration
measure: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
timeFrame: Phase Ib only, up to 3 months after first study drug administration
measure: Elimination half-life (T1/2)
timeFrame: Phase Ib only, up to 3 months after first study drug administration
measure: Systemic clearance (CL)
timeFrame: Phase Ib only, up to 3 months after first study drug administration
measure: Apparent volume of distribution at steady-state (Vss)
timeFrame: Phase Ib only, up to 3 months after first study drug administration
measure: Accumulation Ratio (AR) after multiple dosing
timeFrame: Phase Ib only, up to 3 months after first study drug administration
measure: Incidence of positive ADA
timeFrame: Phase Ib only, up to the 30-day safety follow-up visit after EOT
measure: Clinical benefit rate(CBR) as assess by RECIST v1.1
timeFrame: 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:
measure: Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0
timeFrame: Phase II, screening up to follow-up (30 days after the last dose)
measure: Maximum serum concentration (Cmax) of EMB-01
timeFrame: Phase II, up to 3 months after first study drug administration
measure: Trough serum concentration (Ctrough) of EMB-01
timeFrame: Phase II, predose, through treatment completion, an average of 1 year
measure: Incidence of positive ADA
timeFrame: Phase II , up to the 30-day safety follow-up visit after EOT
measure: Best Overall Response (BOR) as assessed by RECIST v1.1
timeFrame: 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
measure: Objective Response Rate (ORR) as assessed by RECIST v1.1
timeFrame: 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
measure: Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1
timeFrame: 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
measure: Disease Control Rate (DCR) as assess by RECIST v1.1
timeFrame: 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
measure: Progression-Free Survival (PFS) as assess by RECIST v1.1
timeFrame: 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
measure: Clinical benefit rate(CBR) as assess by RECIST v1.1
timeFrame: 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
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Beijing
country: China
facility: Beijing cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Lanzhou
country: China
facility: Gansu Provincial Hospital
city: Qingdao
country: China
facility: The Affiliated hospital of Qingdao University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
Study officials:
References: