This Study is to Evaluate Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors.

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II, Open-Label, Dose Escalation and Cohort Expansion Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors.

Conditions
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Metastatic Solid Tumors, Locally Advanced Solid Tumors

Intervention / Treatment
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* Drug: OBI-888
* Drug: OBI-888
* Device: Globo H IHC Assay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet all of the following criteria in order to be included in the study: Male or female patients, 18 years of age or older at the time of consent. Provide written informed consent prior to performing any study-related procedure. Histologically or cytologically confirmed patients with advanced or metastatic solid tumors for both Dose Escalation and Expansion cohort. 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. Measurable disease (i.e., at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 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 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. 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. Cannot be breast feeding. 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: 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. 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. 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. 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. 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. Patients with a history of solid organ transplant. 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. Receipt of any prior therapy targeting Globo H. Known hypersensitivity to OBI 888 or its excipients. Has known, untreated central nervous system metastases and/or leptomeningeal metastases. 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. Is receiving any concurrent prohibited medication

Ages Eligible for Study
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Minimum Age: 18 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: OBI-888 Escalation Phase<br>Part A: Three cohorts of escalating dose levels of OBI-888 5, 10, and 20 mg/kg liquid form for intravenous infusion to establish maximum tolerated dose (MTD). | Drug: OBI-888<br>* For the dose-escalation phase, OBI-888 will be given weekly at the dose levels of 5, 10, and 20 mg/kg.<br>Device: Globo H IHC Assay<br>* This assay will be used to identify eligible patients who may clinically benefit from the OBI-888 treatment, defined by Globo H expression.<br>|
| Experimental: OBI-888 Expansion Phase<br>Part B: Five cohorts at dose level 20 mg/kg of liquid form OBI-888 for intravenous infusion. | Drug: OBI-888<br>* For the dose-expansion phase, OBI-888 will be given weekly at 20 mg/kg dose level.<br>Device: Globo H IHC Assay<br>* This assay will be used to identify eligible patients who may clinically benefit from the OBI-888 treatment, defined by Globo H expression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of dose-limiting toxicities (DLTs) | Percentage of patients with dose-limiting toxicities (DLTs) observed | first 28 days in escalation phase | 
| Identification of a maximum tolerated dose of OBI-888 | Percentage of patients with adverse events/serious adverse events and laboratory abnormalities as graded by NCI CTCAE version 4.03 | Week 1 to Week 53 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of preliminary clinical activity profile (objective response rate [ORR], clinical benefit rate [CBR], duration of response (DOR), and PFS) of OBI-888 in patients. | Percentage of patients with ORR, CBR, duration of response (DOR), and PFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and immune-related response criteria (irRC) | Week 1 to Week 53 | 
| Measurement of the OBI-888 immunogenicity (anti-drug antibodies [ADAs]) in patients. | Percentage of patients with anti-OBI-888 antibodies in blood. | Week 1 to Week 53 | 
| Pharmacokinetics (PK) - Maximum serum concentrations (Cmax) | PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1 | Week 1 | 
| PK - total exposure Area Under Curve (AUC) | PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1 | Week 1 | 
| PK - elimination half-life (t1/2), | PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1 | Week 1 | 
| PK - clearance (Cl) | PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1 | Week 1 | 
| PK - time to reach maximum concentration (Tmax) | PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1 | Week 1 | 
| PK - volume of distribution (Vd) | PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1 | Week 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mAbs, monoclonal antibodies