Clinical trial NCT03573544: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Solid Tumors
Locally Advanced Solid Tumors
Keywords: mAbs
monoclonal antibodies
Lead sponsor: OBI Pharma, Inc
Sponsor class: INDUSTRY
First posted: 2018-06-29
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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 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

Primary outcomes:
measure: Clinical Benefit Rate (CR, PR, SD) (%)
timeFrame: Every 8 weeks (±1 week) for 6 months, then every 12 weeks (±1 week) until progression or off-study criteria, up to 1 year.
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic Torrey Pines
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Germantown
country: United States
facility: West Cancer Center and Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Apostolia Tsimberidou, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: