Metastatic Gastrointestinal Carcinoid Tumor, Neoplasm Metastasis, Neoplasms
Conditions
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
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.
Interventions
DRUGEMB-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).
Sponsors
Labcorp Corporation of America Holdings, Inc
Shanghai EpimAb Biotherapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Clinical benefit rate(CBR) 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 | Disease Control Rate (DCR) 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 | Progression-Free Survival (PFS) as assess by RECIST v1.1 |
| Maximum serum concentration (Cmax) of EMB-01 | Phase Ib only, up to 3 months after first study drug administration | Maximum serum concentration (Cmax) of EMB-01 |
| Trough serum concentration (Ctrough) of EMB-01 | Phase Ib only, predose, through treatment completion, an average of 1 year | Trough serum concentration (Ctrough) of EMB-01 |
| 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 (pre-dose) to the time of the dosing interval (AUC0-t) |
| 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 | Area under the concentration-time curve from time 0 to infinity (AUC0-inf) |
| Elimination half-life (T1/2) | Phase Ib only, up to 3 months after first study drug administration | Elimination half-life (T1/2) |
| Apparent volume of distribution at steady-state (Vss) | Phase Ib only, up to 3 months after first study drug administration | Apparent volume of distribution at steady-state (Vss) |
| Accumulation Ratio (AR) after multiple dosing | Phase Ib only, up to 3 months after first study drug administration | Accumulation Ratio (AR) after multiple dosing |
| Incidence of positive ADA | Phase Ib only, up to the 30-day safety follow-up visit after EOT | Incidence of positive ADA |
| 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) | Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0 |
| 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 | Best Overall Response (BOR) as assessed by RECIST v1.1 |
| Systemic clearance (CL) | Phase Ib only, up to 3 months after first study drug administration | Systemic clearance (CL) |
| 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 | Objective Response Rate (ORR) as assessed 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 | Duration of Response (DoR) as assess by RECIST v1.1 as assess by RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum serum concentration (Cmax) of EMB-01 | Phase II, up to 3 months after first study drug administration | Maximum serum concentration (Cmax) of EMB-01 |
| Trough serum concentration (Ctrough) of EMB-01 | Phase II, predose, through treatment completion, an average of 1 year | Trough serum concentration (Ctrough) of EMB-01 |
| Incidence of positive ADA | Phase II , up to the 30-day safety follow-up visit after EOT | Incidence of positive ADA |
| 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 | Best Overall Response (BOR) 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 | Objective Response Rate (ORR) as assessed 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 | Duration of Response (DoR) as assess by RECIST v1.1 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 | Disease Control Rate (DCR) 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 | Progression-Free Survival (PFS) 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 | Clinical benefit rate(CBR) as assess by RECIST v1.1 |
| 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) | Number of participants with Adverse Events and Serious Adverse Events as assessed by CTCAE v5.0 |
Countries
China, United States
Contacts
Primary ContactRong Wang, M.Sc
Backup ContactDi Hu, M.Sc
Outcome results
None listed