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

NCT03573544

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: OBI-888-001
  • NCT ID: NCT03573544

Conditions

  • Metastatic Solid Tumors
  • Locally Advanced Solid Tumors

Interventions

DrugSynonymsArms
OBI-888OBI-888 Escalation Phase
OBI-888OBI-888 Expansion Phase

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
OBI-888 Escalation PhaseExperimentalPart 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).
  • OBI-888
OBI-888 Expansion PhaseExperimentalPart B: Five cohorts at dose level 20 mg/kg of liquid form OBI-888 for intravenous infusion.
  • OBI-888

Eligibility Criteria

        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 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:

        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 6 weeks, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measurement of dose-limiting toxicities (DLTs)
Time Frame:first 28 days in escalation phase
Safety Issue:
Description:Percentage of patients with dose-limiting toxicities (DLTs) observed

Secondary Outcome Measures

Measure: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.
Time Frame:Week 1 to Week 53
Safety Issue:
Description: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)
Measure:Measurement of the OBI-888 immunogenicity (anti-drug antibodies [ADAs]) in patients.
Time Frame:Week 1 to Week 53
Safety Issue:
Description:Percentage of patients with anti-OBI-888 antibodies in blood.
Measure:Pharmacokinetics (PK) - Maximum serum concentrations (Cmax)
Time Frame:Week 1
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1
Measure:PK - total exposure Area Under Curve (AUC)
Time Frame:Week 1
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1
Measure:PK - elimination half-life (t1/2),
Time Frame:Week 1
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1
Measure:PK - clearance (Cl)
Time Frame:Week 1
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1
Measure:PK - time to reach maximum concentration (Tmax)
Time Frame:Week 1
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1
Measure:PK - volume of distribution (Vd)
Time Frame:Week 1
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected on Dose 1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:OBI Pharma, Inc

Trial Keywords

  • mAbs
  • monoclonal antibodies

Last Updated

September 5, 2019