Trial of Active Immunotherapy With OBI-833 (Globo H-CRM197) in Advanced/Metastatic Gastric, Lung, Colorectal or Breast Cancer Subjects

An Open-Label Study to Assess the Safety, Tolerability, and Efficacy of Active Immunotherapy With Dose Escalation and Cohort Expansion of OBI-833 (Globo H-CRM197) in Advanced/Metastatic Gastric, Lung, Colorectal, or Breast Cancer Subjects

The purpose of this clinical study is to assess the safety and tolerability and efficacy of active immunotherapy with dose escalation and cohort expansion of OBI-833 in advanced/metastatic gastric, lung, colorectal, or breast cancer subjects.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer; Metastatic Lung Cancer; Metastatic Breast Cancer; Metastatic Gastric Cancer
• Intervention / Treatment: Drug: OBI-833/OBI-821

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University Shuang Ho Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11031
    • Taipei Medical University Hospital
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects ≥21 years of age
2. Dose escalation phase: Histologically or cytologically confirmed diagnosis of gastric, lung, colorectal or breast cancer on file Cohort expansion phase: Histologically or cytologically confirmed diagnosis of Globo H-positive NSCLC

3. Dose escalation: Subjects with recurrent or metastatic incurable disease that failed to respond to at least one line of anticancer standard therapy and for which standard treatment is no longer effective or tolerable.

   Cohort expansion phase: Subjects with recurrent or metastatic NSCLC who have achieved stable disease (SD), or partial response (PR) status after at least 1 regimen of anticancer therapy (i.e., chemotherapy, or targeted therapy, or PD-1/PD-L1 antagonists either alone or in combination) , and there are no standard treatments available except permitted Target or PD-1/PD-L1 therapies

4. Measurable disease (i.e., present with at least one measurable lesion per RECIST, version 1.1.

5. Dose Escalation Phase: No known central nervous system (CNS) metastases or neurological symptoms possibly related to active CNS metastasis in Dose Escalation Phase.

   Cohort Expansion Phase: Subjects with asymptomatic CNS metastases for at least four weeks before study drug treatment

6. Performance status: ECOG ≤ 1

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

   AST/ALT ≤ 3X ULN (upper limit of normal) AST/ALT ≤ 5X ULN [with underlying liver metastasis] Total bilirubin ≤ 2.0 X ULN Serum creatinine ≤ 1.5X ULN ANC ≥ 1500 /µL Platelets > 100,000/µL

8. Subjects of child-bearing potential must agree to use acceptable contraceptive methods during treatment and until the end of the study. Subject not of childbearing potential (i.e., permanently sterilized, postmenopausal) can be included in study. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.
9. Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.

Exclusion Criteria:

1. Patients who have not received standard chemotherapy, hormonal or targeted therapy for their underlying advanced/metastatic cancer.
2. Subjects who are pregnant or breast-feeding at entry.
3. Subjects with splenectomy.
4. Subjects with known or clinically manifest, symptomatic CNS metastases in Dose Escalation Phase.
5. Subjects with HIV infection, active hepatitis B infection or active hepatitis C infection.

6. Subjects with any autoimmune disorders requiring iv/oral steroids or immunosuppressive or immunomodulatory therapies.

   - e.g., Type 1 juvenile onset diabetes mellitus, antibody positive for rheumatoid arthritis, Grave's disease, Hashimoto's thyroiditis, lupus, scleroderma, systemic vasculitis, hemolytic anemia, immune mediated thrombocytopenia, etc.

7. Subjects with any known uncontrolled inter-current 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. Dose escalation phase: Subjects with any of the following MEDICATIONS within 4 weeks prior to IP treatment, except permitted therapies as listed in section 7.1:

   • Chemotherapeutic Agent
   • Immunotherapy [mAbs, Interferons, Cytokines (except GCSF)]
   • Immunosuppressants (e.g., cyclosporin, rapamycin, tacrolimus, rituximab, alemtuzumab, natalizumab, etc.).
   • IV/oral steroids except single prophylactic use in CT/MRI scan or other one-time use in approved indications. The interval between IV/oral steroids administration and first dose of OBI-833/OBI-821 must be more than pharmacological duration or 5 half-lives of administered steroids, whichever is the longer. Uses of inhaled and topical use of steroids are allowed.
   • Another investigational drug

   Cohort Expansion Phase: Subjects with any of the following MEDICATIONS within 4 weeks prior to IP treatment, except permitted therapies:

   • Chemotherapeutic Agent
   • Immunotherapy [Interferons, Cytokines] (except PD-1/PD-L1 antagonists)
   • Immunosuppressants (e.g., cyclosporin, rapamycin, tacrolimus, rituximab, alemtuzumab, natalizumab, etc.).
   • IV/oral steroids except single prophylactic use in CT/MRI scan or other one-time use in approved indications. The interval between IV/oral steroids administration and first dose of OBI-833/OBI-821 must be more than pharmacological duration or 5 half-lives of administered steroids, whichever is longer. Uses of inhaled and topical steroids are allowed.
   • Another investigational drug
9. Subjects with pleural effusions and/or ascites, due to malignancy, requiring paracentesis every 2 weeks or more frequently.
10. Subjects with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in the study drugs.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; Each subject will be given a total of 10 doses of OBI-833/OBI-821 subcutaneously at weeks 1,2,3,4,6,8,12,16,20,and 24 (Visits 1,2,3,4,5,6,7,8,9 and 10, respectively). Post treatment, subjects will be continually evaluated for safety and immune response every 4 weeks until the end of study, which is 12 weeks after the last dose, i.e., week 36. Subsequently, subjects will be followed for survival every 8 weeks up to 12 months after the end of study.	Drug: OBI-833/OBI-821
Experimental: Cohort expansion phase; Each subject will be given OBI-833/OBI-821 at Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, and every 8 weeks thereafter (Visits 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and every 8 weeks thereafter) until disease progression. For the subjects discontinued treatment because of disease progression, subjects will be continually evaluated for safety and immune response every 8 weeks until the end of the study, which is 24 weeks after the last dose.	Drug: OBI-833/OBI-821

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-emergent Adverse Events	Approximately 13 weeks for dose escalation cohorts and 44 weeks for expansion cohort

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Post-baseline Anti-Globo H Antibody Responses	Anti-Globo H IgM and IgG concentrations were measured using a chemical binding assay.	Approximately 13 weeks for dose escalation cohorts and 44 weeks for expansion cohort

Collaborators and Investigators

• Sponsor: OBI Pharma, Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): December 22, 2020
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: December 2, 2014
• First Submitted That Met QC Criteria: December 3, 2014
• First Posted (Estimate): December 8, 2014

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: OBI-833-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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