To Evaluate OBI-833/OBI-821 in Patients With Locally Advanced, Globo H-Positive Esophageal Cancer for Recurrence

A Randomized, Open-Label, Phase 2 Study to Evaluate Adjuvant OBI-833/OBI-821 Therapy in Patients With Locally Advanced, Globo H-Positive Esophageal Cancer at High Risk for Recurrence

A Phase 2 Study to Evaluate Adjuvant OBI-833/OBI-821 Therapy in Patients With Locally Advanced, Globo H-Positive Esophageal Cancer at High Risk for Recurrence

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Biological: OBI-833/OBI-821

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jang-Ming Lee; Phone Number: 63940 +886-2-23123456; Email: jangminglee@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Jang-Ming Lee; Phone Number: 263940 +886-2-23123456; Email: jangminglee@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients, 20 years of age or older at the time of consent.
2. Pathologically or cytologically confirmed diagnosis of esophageal cancer (including squamous cell carcinoma and adenocarcinoma) whose postneoadjuvant pathologic stage is ypT1-4 AND ypN1-3 according to the AJCC Cancer Staging System, 8th Edition.
3. Patients have been treated with preoperative cisplatin-based chemoradiotherapy followed by esophagectomy with lymph node dissection for locally advanced esophageal cancer (defined by the above criterion).
4. Postneoadjuvant pathologic staging: ypT1-4 and ypN1-3.
5. Globo H IHC H-score ≥1 in the surgical tumor specimen from the primary site/or lymph node (if the primary site is not available). The Globo H expression will be determined by a qualified laboratory.
6. R0 (no residual tumor on the surgical margin of the resected tumor specimen).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Organ Function Requirements - Subjects must have adequate organ functions as defined below:

   • AST/ALT ≤ 3X ULN (upper limit of normal)
   • Total bilirubin ≤ 2X ULN
   • Serum creatinine ≤ 1.5X ULN
   • ANC ≧ 1,500 /μL
   • Platelets ≧ 100,000/μL
9. 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.
10. Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.

Exclusion Criteria:

1. Subjects who cannot be randomized within 8 weeks after the esophageal cancer surgery.
2. Subjects who are pregnant or breast-feeding at entry.
3. Subjects with splenectomy.
4. Has prior malignancy, except (a) adequately treated basal cell or squamous cell skin cancer; (b) in situ cervical cancer; (c) previously diagnosed malignancy which has been adequately treated and shown no evidence of recurrence for more than 5 years.
5. Subjects with HIV infection, active hepatitis B infection, or active hepatitis C infection.

6. Subjects 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.

7. Subjects 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.

8. Subjects who have received any of the following medications within 4 weeks prior to randomization:

   • 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
9. 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.
10. Subjects 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 as unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OBI-833/OBI-821; OBI-833 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 a carrier protein. OBI-821 is a purified saponin adjuvant Dosage form: solution Dosage:30 μg OBI-833/100 μg OBI-821, subcutaneous injection, Frequency: weekly for 4 doses (weeks 1, 2, 3, 4), then every 2 weeks for 2 doses (weeks 6, 8), then every 4 weeks for 4 doses (weeks 12, 16, 20, 24), and then every 8 weeks until disease recurrence, intolerable adverse events/toxicity, consent withdrawal, death, or up to 80 weeks from randomization.	Biological: OBI-833/OBI-821; OBI-833 and OBI-821 are individually formulated into separate glass vials. The articles are mixed prior to subcutaneous administration at the clinic.
No Intervention: Observation; Patients will be randomized into OBI-833/OBI-821 (experimental) arm or observation arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival rate	To evaluate the effect of OBI-833/OBI-821 treatment on improving recurrence-free survival in patients with locally advanced, Globo H-positive esophageal cancer in the adjuvant setting	one year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Jang-Ming Lee, Department of Surgery, National Taiwan University Hospital. Taipei, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Recurrence; Esophageal Neoplasms
• Other Study ID Numbers: 202106018MIPB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No