Locally Advanced Solid Tumors, Metastatic Solid Tumors
Conditions
Keywords
mAbs, monoclonal antibodies
Brief summary
The purpose of this study is to establish the maximum tolerated dose (MTD) of OBI-888 as monotherapy. And to characterize the safety and preliminary clinical activity profile of the MTD dose of OBI-888 administered as monotherapy in patients with locally advanced or metastatic solid tumors.
Interventions
DRUGOBI-888
For the dose-escalation phase, OBI-888 will be given weekly at the dose levels of 5, 10, and 20 mg/kg.
DEVICEGlobo H IHC Assay
This assay will be used to identify eligible patients who may clinically benefit from the OBI-888 treatment, defined by Globo H expression.
Sponsors
OBI Pharma, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria in order to be included in the study: 1. Male or female patients, 18 years of age or older at the time of consent. 2. Provide written informed consent prior to performing any study-related procedure. 3. Histologically or cytologically confirmed patients with advanced or metastatic solid tumors for both Dose Escalation and Expansion cohort. 4. Patients must have been treated with established standard-of-care therapy, or physicians have determined that such established therapy is not sufficiently efficacious, or patients have declined to receive standard-of-care therapy. 5. Measurable disease (i.e., at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Adequate organ function defined as: * Hepatic: * Serum alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN), ≤5 × ULN in the presence of liver metastases * Serum aspartate aminotransferase (AST) ≤3 × ULN, ≤5 × ULN in presence of liver metastases * Serum bilirubin ≤1.5 × ULN * Renal: * Creatinine clearance \>30 mL/minute using Cockcroft Gault equation * Hematologic: * Absolute neutrophil count ≥1000/µL * Platelets ≥75,000/µL * Hemoglobin ≥8 g/dL 8. Patient is willing and able to comply with all protocol required assessments, visits, and procedures, including pretreatment tumor biopsy. Archival tumor biopsies are acceptable at baseline. 9. Females of childbearing potential must have negative urine or serum pregnancy test prior to starting study therapy, and agree to use a reliable form of contraceptive during the study treatment period and for at least 120 days following the last dose of study drug. 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. Male patients must agree to use an adequate method of contraception during the study treatment period and for at least 120 days following the last dose of study drug. 10. Cannot be breast feeding. 11. Patients in Part B (Cohort expansion); must have a qualifying, documented Globo H H-score in sponsor-selected tumor types to be enrolled in the respective cohort: * Cohort 1: Pancreatic cancer * Cohort 2: Esophageal cancer * Cohort 3: Gastric cancer * Cohort 4: Colorectal cancer * Cohort 5: Basket (any solid tumor type other than those included in Cohorts 1 through 4)
Exclusion criteria
Patients meeting any of the following criteria are ineligible to participate in this study: 1. Less than 3 weeks, from prior cytotoxic chemotherapy or radiation therapy; and less than 5 half-lives or 3 weeks from biological therapies, whichever is shorter, prior to the first dose of OBI-888. 2. Has undergone a major surgical procedure (as defined by the investigator) or significant traumatic injury within 28 days prior to the first dose of OBI-888. 3. Presence of an active autoimmune or inflammatory disease requiring systemic treatment within the past 2 months or a documented history of clinically severe autoimmune disease that requires systemic steroids or other immunosuppressive medications. Local steroid injections, intermittent use of topical, inhaled, ophthalmologic, intra-articular, topical, or intranasal corticosteroids, or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent would not be excluded from the study. 4. Presence of primary immunodeficiency or receiving systemic steroids of \>10 mg/day of prednisone or equivalent or other immunosuppressive agents within 14 days prior to the first dose of OBI 888. 5. Has active bacterial, viral, fungal, or mycobacterial infection requiring systemic therapy, including known infection with human immunodeficiency virus (HIV) or active infection with hepatitis B virus or hepatitis C virus. 6. Patients with a history of solid organ transplant. 7. 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 4.03), except for alopecia and laboratory values listed in the inclusion criteria. 8. Receipt of any prior therapy targeting Globo H. 9. Known hypersensitivity to OBI 888 or its excipients. 10. Has known, untreated central nervous system metastases and/or leptomeningeal metastases. 11. Any medical co morbidity or psychiatric illness that is life threatening or, in the opinion of the Investigator, renders the patient unsuitable for participation in a clinical trial due to possible noncompliance, would place the patient at an unacceptable risk and/or potential to affect interpretation of results of the study. 12. Is receiving any concurrent prohibited medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CR, PR, SD) (%) | Every 8 weeks (±1 week) for 6 months, then every 12 weeks (±1 week) until progression or off-study criteria, up to 1 year. | Assessment of OBI-888 clinical benefit rate for dose escalation and cohort expansion phases of the OBI-888-001 study. |
Countries
Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A, Dose Escalation - OBI-888 5 mg/kg OBI-888 5 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 5 |
| Part A, Dose Escalation - OBI-888 10 mg/kg OBI-888 10 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 3 |
| Part A, Dose Escalation - OBI-888 20 mg/kg OBI-888 20 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 6 |
| Part B, Cohort Expansion - Cohort 1, Pancreatic OBI-888 20 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 8 |
| Part B, Cohort Expansion - Cohort 2, Esophageal OBI-888 20 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 7 |
| Part B, Cohort Expansion - Cohort 3, Gastric OBI-888 20 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 8 |
| Part B, Cohort Expansion - Cohort 4, Colorectal OBI-888 20 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 9 |
| Part B, Cohort Expansion - Cohort 5, Basket OBI-888 20 mg/kg was administered as an IV infusion for approximately 90 minutes (±10 minutes) on Days 1, 8, 15 and 22 of each 28-day cycle for 2 cycles | 8 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 | 1 | 0 | 2 | 0 |
| Overall Study | Disease progression | 3 | 3 | 6 | 4 | 5 | 7 | 6 | 7 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 1 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Part B, Cohort Expansion - Cohort 5, Basket | Part B, Cohort Expansion - Cohort 4, Colorectal | Part A, Dose Escalation - OBI-888 5 mg/kg | Part B, Cohort Expansion - Cohort 3, Gastric | Part B, Cohort Expansion - Cohort 2, Esophageal | Part B, Cohort Expansion - Cohort 1, Pancreatic | Part A, Dose Escalation - OBI-888 20 mg/kg | Part A, Dose Escalation - OBI-888 10 mg/kg |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 11.81 | 60.6 years STANDARD_DEVIATION 8.07 | 52.9 years STANDARD_DEVIATION 14.84 | 51 years STANDARD_DEVIATION 12.86 | 64.9 years STANDARD_DEVIATION 9.69 | 57.4 years STANDARD_DEVIATION 9.36 | 63.8 years STANDARD_DEVIATION 13.29 | 64.5 years STANDARD_DEVIATION 12.1 | 57.7 years STANDARD_DEVIATION 9.45 |
| Race/Ethnicity, Customized Ethnicity (NIH/OMB) East Asian | 19 Participants | 3 Participants | 0 Participants | 0 Participants | 7 Participants | 6 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity (NIH/OMB) Other | 24 Participants | 3 Participants | 8 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity (NIH/OMB) Unknown or not reported | 9 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants | 4 Participants | 0 Participants | 0 Participants | 7 Participants | 6 Participants | 3 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 29 Participants | 4 Participants | 9 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Female | 27 Participants | 5 Participants | 2 Participants | 5 Participants | 3 Participants | 0 Participants | 6 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 27 Participants | 3 Participants | 7 Participants | 0 Participants | 5 Participants | 7 Participants | 2 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 | 0 / 6 | 1 / 8 | 0 / 7 | 0 / 8 | 1 / 9 | 0 / 8 |
| other Total, other adverse events | 5 / 5 | 3 / 3 | 5 / 6 | 8 / 8 | 6 / 7 | 8 / 8 | 9 / 9 | 8 / 8 |
| serious Total, serious adverse events | 1 / 5 | 1 / 3 | 0 / 6 | 8 / 8 | 2 / 7 | 5 / 8 | 5 / 9 | 2 / 8 |
Outcome results
Primary
Clinical Benefit Rate (CR, PR, SD) (%)
Assessment of OBI-888 clinical benefit rate for dose escalation and cohort expansion phases of the OBI-888-001 study.
Time frame: Every 8 weeks (±1 week) for 6 months, then every 12 weeks (±1 week) until progression or off-study criteria, up to 1 year.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A, Dose Escalation - OBI-888 5 mg/kg | Clinical Benefit Rate (CR, PR, SD) (%) | 20 Percentage |
| Part A, Dose Escalation - OBI-888 10 mg/kg | Clinical Benefit Rate (CR, PR, SD) (%) | 66.7 Percentage |
| Part A, Dose Escalation - OBI-888 20 mg/kg | Clinical Benefit Rate (CR, PR, SD) (%) | 16.7 Percentage |
| Part B, Cohort Expansion - Cohort 1, Pancreatic | Clinical Benefit Rate (CR, PR, SD) (%) | 12.5 Percentage |
| Part B, Cohort Expansion - Cohort 2, Esophageal | Clinical Benefit Rate (CR, PR, SD) (%) | 14.3 Percentage |
| Part B, Cohort Expansion - Cohort 3, Gastric | Clinical Benefit Rate (CR, PR, SD) (%) | 25 Percentage |
| Part B, Cohort Expansion - Cohort 4, Colorectal | Clinical Benefit Rate (CR, PR, SD) (%) | 22.2 Percentage |
| Part B, Cohort Expansion - Cohort 5, Basket | Clinical Benefit Rate (CR, PR, SD) (%) | 25 Percentage |