Trial Title:
Phase 2 Study: OBI-833/OBI-821 Maintenance for Globo H+ Advanced Biliary Tract Cancer After Gemcitabine/Cisplatin
NCT ID:
NCT06490198
Condition:
Cholangiocarcinoma
Chemotherapy Effect
Immunotherapy
Conditions: Official terms:
Cholangiocarcinoma
Biliary Tract Neoplasms
Conditions: Keywords:
Cholangiocarcinoma
Immunotherapy
Chemotherapy
Globo-H
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
OBI-833/OBI-821
Description:
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.
Arm group label:
Globo-H
Other name:
Globo H-CRM197
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.
Detailed description:
This clinical trial is a single-arm, phase 2 study evaluating OBI-833/OBI-821 as
maintenance therapy in patients with Globo H-positive advanced biliary tract cancer who
have not progressed on first-line gemcitabine and cisplatin chemotherapy. The study is
grounded in the challenging prognosis of biliary tract cancer, including
cholangiocarcinoma, which has limited treatment options. Currently, the standard
first-line therapy is gemcitabine plus cisplatin, but progression-free survival remains
short at around 6 months, highlighting the need for improved treatment strategies.
The investigational therapy, OBI-833, is a glycoconjugate vaccine targeting Globo H, a
tumor-associated carbohydrate antigen expressed in many epithelial cancers. It is used in
combination with OBI-821, an adjuvant designed to enhance the immune response. Previous
studies have demonstrated that OBI-833/OBI-821 can elicit immune responses and provide
disease stabilization in some cancer patients. Notably, Globo H expression has been
detected in about 41% of intrahepatic cholangiocarcinoma specimens, providing a rationale
for investigating this approach in biliary tract cancer.
The study design involves enrolling 30 patients in a single-arm trial. Eligible patients
must have Globo H-positive advanced biliary tract cancer that has not progressed after
3±1 months of first-line gemcitabine/cisplatin therapy. Patients will receive
OBI-833/OBI-821 subcutaneously on a gradually decreasing frequency schedule for up to 80
weeks, while continuing their gemcitabine/cisplatin regimen. The primary endpoint of the
study is progression-free survival, with secondary endpoints including overall survival,
tumor response, safety, and correlations between Globo H expression/antibodies and
survival outcomes.
To ensure safety, the study incorporates a lead-in safety cohort of 6 patients before
proceeding to full enrollment. Following the treatment period, patients will be followed
for survival for up to 12 months after the end of treatment. This single-arm design
allows for an efficient assessment of efficacy signals that could inform potential
further development of this therapeutic approach.
The overall aim of the study is to evaluate whether adding OBI-833/OBI-821 maintenance
therapy can prolong disease control in this patient population with high unmet medical
need. By focusing on patients with Globo H-positive tumors who have initially responded
to standard chemotherapy, the study seeks to explore a potentially targeted approach to
maintaining and extending the benefits of first-line treatment in advanced biliary tract
cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
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.
Gender:
All
Minimum age:
20 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chang Gung Memorial Hospital Linkou Branch
Address:
City:
Taoyuan
Zip:
333
Country:
Taiwan
Facility:
Name:
Chang-Gung Memorial Hospital, Linkou Branch
Address:
City:
Taoyuan
Country:
Taiwan
Start date:
July 31, 2024
Completion date:
July 31, 2027
Lead sponsor:
Agency:
Chang Gung Memorial Hospital
Agency class:
Other
Source:
Chang Gung Memorial Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06490198
