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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Metastatic Gastric Cancer, Metastatic Breast Cancer, Metastatic Colorectal Cancer, Metastatic Lung Cancer

Intervention / Treatment
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* Drug: OBI-833/OBI-821


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects ≥21 years of age 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 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 Measurable disease (i.e., present with at least one measurable lesion per RECIST, version 1.1. 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 Performance status: ECOG ≤ 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 [with underlying liver metastasis] Total bilirubin ≤ 2.0 X ULN Serum creatinine ≤ 1.5X ULN ANC ≥ 1500 /µL Platelets > 100,000/µL 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. Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines. Exclusion Criteria: Patients who have not received standard chemotherapy, hormonal or targeted therapy for their underlying advanced/metastatic cancer. Subjects who are pregnant or breast-feeding at entry. Subjects with splenectomy. Subjects with known or clinically manifest, symptomatic CNS metastases in Dose Escalation Phase. Subjects with HIV infection, active hepatitis B infection or active hepatitis C infection. 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. 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. 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 Subjects with pleural effusions and/or ascites, due to malignancy, requiring paracentesis every 2 weeks or more frequently. Subjects with any known severe allergies (e.g., anaphylaxis) to any active or inactive ingredients in the study drugs.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>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<br> <br> |
| Experimental: Cohort expansion phase<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |