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

NCT06490198 | Not Yet Recruiting Phase 1

• 1 other identifier: 202400601A0C601
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase 2 clinical trial protocol for evaluating the efficacy and safety of OBI-833/OBI-821, a carbohydrate-conjugate vaccine combined with an immune adjuvant, as maintenance therapy in combination with first-line gemcitabine and cisplatin chemotherapy for patients with Globo H-positive advanced biliary tract cancer. The study is designed as a single-arm trial with 30 patients who have achieved stable disease, partial response, or complete response after 3±1 months of initial chemotherapy. The primary endpoint is progression-free survival, with secondary endpoints including overall survival, tumor response, and safety profile. The treatment regimen involves subcutaneous injections of OBI-833/OBI-821 on a gradually decreasing frequency schedule for up to 80 weeks. The trial also includes exploratory objectives to assess immune responses and biomarkers. This study aims to address the unmet need for improved treatment options in advanced biliary tract cancer by leveraging the potential of immunotherapy targeting the Globo H antigen.

Conditions

Cholangiocarcinoma; Chemotherapy Effect; Immunotherapy

Keywords

Cholangiocarcinoma; Immunotherapy; Chemotherapy; Globo-H

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  The time from start of treatment until disease progression or death from any cause

  12 to 18 months of subject recruitment, 80 weeks of OBI-833/OBI-821 treatment, and another 1 year for overall survival follow-up.

Secondary Outcomes (4)

• Overall survival

  12 to 18 months of subject recruitment, 80 weeks of OBI-833/OBI-821 treatment, and another 1 year for overall survival follow-up.

• Best overall tumor response

  12 to 18 months of subject recruitment, 80 weeks of OBI-833/OBI-821 treatment, and another 1 year for overall survival follow-up.

• Adverse events

  12 to 18 months of subject recruitment, 80 weeks of OBI-833/OBI-821 treatment, and another 1 year for overall survival follow-up.

• Correlation between anti-Globo H IgM and IgG concentrations and survival

  12 to 18 months of subject recruitment, 80 weeks of OBI-833/OBI-821 treatment, and another 1 year for overall survival follow-up.

Study Arms (1)

Globo-H

EXPERIMENTAL

OBI-833, 30 μg/ OBI-821 100 μg, Subcutaneous injection at Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 56, 64, 72, and 80 weeks

Drug: OBI-833/OBI-821

Interventions

OBI-833/OBI-821 DRUG

OBI-833 is a glycoconjugate that consists of Globo H, a unique tumor-associated carbohydrate antigen (TACA), covalently linked to cross-reacting material 197 (CRM197), an inactive and nontoxic form of diphtheria toxin (DT) acting as the carrier protein. OBI-821 is a saponin-based adjuvant derived from the bark of the Quillaja saponaria Molina tree. It is a purified saponin adjuvant structurally similar to adjuvant QS-21. The OBI-833/OBI-821 combination represents a carbohydrate-conjugate vaccine combined with an immune adjuvant, intended to serve as an active cancer immunotherapy.

Also known as: Globo H-CRM197

Globo-H

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 20 years.
• Histologically confirmed, unresectable advanced or metastatic biliary tract cancer, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma.
• Patient with previously untreated disease if unresectable or metastatic at initial diagnosis will be eligible.
• 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.
• Patient must have a documented Globo H H-score of at least 80 using a validated central IHC assay.
• 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.
• At least one measurable tumor lesion according to RECIST version 1.1 as assessed by the Investigator (local radiological image assessment).
• Life expectancy ≥ 6 months.
• East Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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
• 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.
• Understand and provide a written informed consent document according to institutional guidelines.

You may not qualify if:

• Patient who has CNS metastasis or spinal cord compression.
• Patient who is pregnant or breast-feeding at entry.
• Patient with splenectomy.
• 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.
• 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).
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (2)

Chang Gung Memorial Hospital Linkou Branch

Taoyuan District, 333, Taiwan

Location

Chang-Gung Memorial Hospital, Linkou Branch

Taoyuan District, Taiwan

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Chun-Nan Yeh

  Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chun-Nan Yeh, MD

CONTACT

886-33281200; yehchunnan@gmail.com

Wen-Kuan Huang, PhD

CONTACT

886-33281200

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Department of Surgery, Chang Gung Memorial Hospital, Linkou and Chang Gung University, Taipei, Taiwan

Study Record Dates

• First Submitted: June 30, 2024
• First Posted: July 8, 2024
• Study Start: July 31, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 8, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (2)