Metastatic Breast Cancer, Metastatic Colorectal Cancer, Metastatic Gastric Cancer, Metastatic Lung Cancer
Conditions
Brief 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.
Interventions
DRUGOBI-833/OBI-821
Sponsors
OBI Pharma, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Maximal Post-baseline Anti-Globo H Antibody Responses | Approximately 13 weeks for dose escalation cohorts and 44 weeks for expansion cohort | Anti-Globo H IgM and IgG concentrations were measured using a chemical binding assay. |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation - Cohort 1 10 μg OBI-833/100 μg OBI-821 | 4 |
| Dose Escalation - Cohort 2 30 μg OBI-833/100 μg OBI-821 | 3 |
| Dose Escalation - Cohort 3 100 μg OBI-833/100 μg OBI-821 | 4 |
| Expansion Cohort NSCLC patients receiving 30 μg OBI-833/100 μg OBI-821 | 14 |
| Total | 25 |
Baseline characteristics
| Characteristic | Total | Dose Escalation - Cohort 1 | Expansion Cohort | Dose Escalation - Cohort 3 | Dose Escalation - Cohort 2 |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 1 Participants | 11 Participants | 3 Participants | 2 Participants |
| Age, Continuous | 60.3 years STANDARD_DEVIATION 9.82 | 63 years STANDARD_DEVIATION 10.61 | 59.2 years STANDARD_DEVIATION 10.25 | 58 years STANDARD_DEVIATION 9.42 | 65 years STANDARD_DEVIATION 10.44 |
| Cancer Type Breast | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Cancer Type Colorectal | 8 Participants | 3 Participants | 0 Participants | 4 Participants | 1 Participants |
| Cancer Type Lung | 15 Participants | 1 Participants | 14 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 4 Participants | 14 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 1 Participants | 14 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Taiwan | 16 participants | 1 participants | 14 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 9 participants | 3 participants | 0 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 16 Participants | 3 Participants | 7 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 1 Participants | 7 Participants | 1 Participants | 0 Participants |
| Tumor Globo H Expression | 130.6 scores on a scale STANDARD_DEVIATION 83.77 | — | 130.6 scores on a scale STANDARD_DEVIATION 83.77 | — | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 0 / 3 | 1 / 4 | 3 / 14 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 4 / 4 | 13 / 14 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 3 / 4 | 3 / 14 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events
Time frame: Approximately 13 weeks for dose escalation cohorts and 44 weeks for expansion cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Escalation - Cohort 1 | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 1 Participants |
| Dose Escalation - Cohort 1 | Number of Participants With Treatment-emergent Adverse Events | Any TEAEs | 4 Participants |
| Dose Escalation - Cohort 2 | Number of Participants With Treatment-emergent Adverse Events | Any TEAEs | 3 Participants |
| Dose Escalation - Cohort 2 | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 0 Participants |
| Dose Escalation - Cohort 3 | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 3 Participants |
| Dose Escalation - Cohort 3 | Number of Participants With Treatment-emergent Adverse Events | Any TEAEs | 4 Participants |
| Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events | Serious TEAEs | 3 Participants |
| Expansion Cohort | Number of Participants With Treatment-emergent Adverse Events | Any TEAEs | 13 Participants |
Secondary
Maximal Post-baseline Anti-Globo H Antibody Responses
Anti-Globo H IgM and IgG concentrations were measured using a chemical binding assay.
Time frame: Approximately 13 weeks for dose escalation cohorts and 44 weeks for expansion cohort
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dose Escalation - Cohort 1 | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgM concentration | 4.602 μg/mL |
| Dose Escalation - Cohort 1 | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgG concentration | 5.011 μg/mL |
| Dose Escalation - Cohort 2 | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgG concentration | 1.000 μg/mL |
| Dose Escalation - Cohort 2 | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgM concentration | 2.048 μg/mL |
| Dose Escalation - Cohort 3 | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgM concentration | 3.165 μg/mL |
| Dose Escalation - Cohort 3 | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgG concentration | 2.186 μg/mL |
| Expansion Cohort | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgM concentration | 13.920 μg/mL |
| Expansion Cohort | Maximal Post-baseline Anti-Globo H Antibody Responses | Maximal post-baseline anti-Globo H IgG concentration | 9.472 μg/mL |