1. Age â‰¥18 years. A patient may be of either sex and of any race/ethnicity.
2. Histologically confirmed, chemo-refractory, locally advanced, recurrent or metastatic
gastric (including GE junction), colorectal, or pancreatic adenocarcinoma or biliary
cancer (including cholangiocarcinoma, gallbladder and ampullary carcinomas).
1. Patient must not have curative options available (e.g. a single metastatic focus
in the liver in a patient with MCRC eligible for metastasectomy).
2. Chemo-refractory is defined as:
- • Progression on or following, or intolerant of, at least one prior line of
standard systemic therapy for advanced or metastatic gastric or pancreatic
or biliary cancers.
- • Progression on or following, or intolerant of, at least two prior lines of
standard systemic therapy for advanced or metastatic colorectal cancers.
- • Patients who have progressed/recurred following neoadjuvant/adjuvant
chemotherapy for earlier stage disease, if completed within the previous 6
months, are eligible.
3. Archived tissue must be available for all patients (both dose escalation and expansion
cohorts). Dose Escalation Only-If tissue is not available, patients may still be
considered eligible for enrollment, if all other eligibility criteria are confirmed
and after discussion with and approval by the sponsor medical monitor. Cohort
Expansion Only-Tissue must be to confirmed high expression of AG7 antigen during the
Pre-Screening period, defined as immune reactive score (IRS) â‰¥8, via slides from
original diagnostic biopsy material or biopsy of recurrent/metastatic disease, prior
4. Measurable disease by RECIST 1.1 criteria
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
6. Adequate organ function within 3 weeks prior to first study drug administration as
1. Absolute neutrophil count â‰¥1.5 x 10^9/L,
2. Hemoglobin â‰¥9 g/dL,
3. Platelet count â‰¥100 x 10^9/L,
4. Serum creatinine â‰¤1.5 x upper limit of normal (ULN) or a calculated creatinine
clearance >60 mL/min,
5. Total bilirubin <1.5 x ULN, except for patients with Gilbert's disease who are
eligible if total bilirubin â‰¤ 3 mg/dL.
6. Aspartate aminotransferase (AST)/serum glutamic-oxalacetic transaminase (SGOT)
and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT)
<2.5 x ULN, or, in the presence of documented liver metastases, â‰¤5 x ULN.
7. Ability to adhere to dose and visit schedules.
8. Women of childbearing potential (WOCP) must have a negative pregnancy test result
prior to enrollment. WOCP and men whose partners are WOCP must agree to use a highly
effective method of birth control during the study and for 6 months following the last
dose of study drug. A highly effective method of birth control is defined as one which
results in a low failure rate (less than 1% per year).
9. Ability to provide written informed consent
10. Life expectancy of at least 3 months.
1. Any persistent, unresolved Common Terminology Criteria for Adverse Events (CTCAE)
Grade â‰¥2 drug-related toxicity (except alopecia, erectile impotence, tinnitus, hot
flashes, and loss of libido) associated with previous treatment. Inclusion of patients
with persistent neuropathy or hearing loss Grade â‰¥2 due to previous treatment requires
discussion with the sponsor.
2. Radiation therapy within 2 weeks prior to first study drug administration.
3. Major surgery within 3 weeks prior to first study drug administration.
4. Any chemotherapy within 30 days of enrollment.
5. Participation in any other clinical study with a potentially therapeutic agent or
receipt of another investigational product within 21 days or 5 plasma half-lives,
whichever is longer, prior to first day of drug administration (Day 1).
6. Active central nervous system metastases. Patients with a history of brain metastases
may be eligible, provided they have been definitively treated and are clinically
stable, after discussion with sponsor. Treated or untreated leptomeningeal disease is
7. Known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy.
Note: HIV testing is not required unless there is any clinical suspicion that the
patient might be HIV positive.
8. Known active hepatitis B or C. HBV and HCV tests are required prior to Day 1.
9. Any clinically significant condition or situation, other than the condition being
studied that, in the opinion of the investigator, would impair with their ability to
receive or tolerate the planned treatment, or interfere with the study evaluations or
optimal participation in the study.
10. Pregnancy or breastfeeding.