Phase 2 Study: OBI-833/OBI-821 Maintenance for Globo H+ Advanced Biliary Tract Cancer After Gemcitabine/Cisplatin

1. Aged ≥ 20 years.
2. Histologically confirmed, unresectable advanced or metastatic biliary tract cancer, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma.
3. Patient with previously untreated disease if unresectable or metastatic at initial diagnosis will be eligible.
4. Patient with recurrent disease >6 months after curative surgery or >6 months after the completion of adjuvant therapy (chemotherapy and/or radiation) will be eligible.
5. Patient must have a documented Globo H H-score of at least 80 using a validated central IHC assay.
6. Patient must have received 3±1 months of the first-line GemCis regimen (gemcitabine, 1000 mg/m2 and cisplatin, 25 mg/m2 on days 1 and 8 of each 21-day cycle), have achieved SD, PR, or CR before enrollment (as confirmed by the Investigator), and plan to continue the GemCis regimen.
7. At least one measurable tumor lesion according to RECIST version 1.1 as assessed by the Investigator (local radiological image assessment).
8. Life expectancy ≥ 6 months.
9. East Cooperative Oncology Group (ECOG) performance status of 0 or 1.

10. Organ function requirements - Subjects must have adequate organ functions as defined below:

    AST/ALT ≤ 3X ULN (upper limit of normal); AST/ALT ≤ 5X ULN in the presence of liver metastases Total bilirubin ≤ 2.0 X ULN Serum creatinine ≤ 1.5X ULN ANC ≥ 1,5500 /µL Platelets ≥ 100,000/µL

11. All eligible patients of childbearing potential must use effective contraception during study treatment, and for at least 2 months after the last dose of OBI-833/OBI-821. Subjects not of childbearing potential (i.e., permanently sterilized, postmenopausal) can be included in the study. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.
12. Understand and provide a written informed consent document according to institutional guidelines.

Exclusion Criteria:

1. Patient who has CNS metastasis or spinal cord compression.
2. Patient who is pregnant or breast-feeding at entry.
3. Patient with splenectomy.
4. Patient with HIV infection, active hepatitis B infection, or active hepatitis C infection. Patients with hepatitis B infection under anti-HBV medications are exceptionalcan be included in the study. Patients with hepatitis C infection history but inactive status are exceptionalcan be included in the study.

5. Patient with any autoimmune or other disorders requiring IV/oral steroids or immunosuppressive or immunomodulatory therapies.

   (e.g., type 1 juvenile onset diabetes mellitus, antibody positive for rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, lupus, scleroderma, systemic vasculitis, hemolytic anemia, immune mediated thrombocytopenia, Crohn disease, ulcerative colitis, and psoriasis).

6. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Grade 0 or 1 (using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), except for alopecia and laboratory values listed in the inclusion criteria.
7. A history of other malignancies (except non-melanoma skin carcinoma, carcinoma in situ of the uterine cervix, follicular or papillary thyroid cancer) within 5 years.
8. Patient with any known uncontrolled comorbid illness including ongoing or active infections, symptomatic congestive heart failure (NYHA>2), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

9. Treatment with any of the following therapies within 4 weeks prior to the first dose of OBI-833/OBI-821:

   • Anti-cancer therapies, including chemotherapy and targeted therapy (except the GemCis regimen).
   • Radiotherapy.
   • Immunotherapy, including monoclonal antibodies, cytokines, interferons, and checkpoint inhibitors.
   • Immunosuppressants, including cyclosporin, rapamycin, tacrolimus, rituximab, alemtuzumab, natalizumab, and cyclophosphamide.
   • Other biologics, including G-CSF and other hematopoietic growth factors.
   • Live attenuated vaccines.
   • IV/oral steroids except single prophylactic use in CT/MRI scan or other one-time use in approved indications. Use of inhaled and topical (except on the injection site) steroids is allowed.
   • Alternative and complementary medicine that may affect the immune system.
   • Other investigational drugs.
10. Patient with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in the study drugs.
11. Any other reason that the investigator deems the patient to be unsuitable for the study.