Overview

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.

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.