Trial of Active Immunotherapy With OBI-833 (Globo H-CRM197) in Advanced/Metastatic Gastric, Lung, Colorectal or Breast Cancer Subjects
Condition: Metastatic Gastric Cancer; Metastatic Breast Cancer; Metastatic Colorectal Cancer; Metastatic Lung Cancer
MeSH terms: Breast Neoplasms
Intervention: OBI-833/OBI-821
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.