A Phase I/II Study of OBI-3424 in Subjects with Advanced Solid Tumors

NCT03592264 | Terminated Phase 1 FDA Drug

• 1 other identifier: OBI-3424-001
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 5

Brief Summary

A first-in-human open-label, Phase I/II study to evaluate the safety, tolerability, MTD/RP2D, PK, and preliminary efficacy of OBI-3424 administered as a single agent.

Conditions

Solid Tumor; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (10)

• Incidence and severity of adverse events (AEs)

  Adverse events will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.

  Adverse events will be noted as it occurs. Timeframe for measure begins after first administration of study drug until 30 days after last dose of study drug. Study duration defined as up to 2 years from the first dose.

• Assess safety changes in electrocardiogram (ECG)

  Resting 12-lead ECGs will be obtained from all subjects' pre-OBI-3424 infusion and within 15 minutes post-OBI-3424 infusion in order to assess any impact OBI-3424 may have on the QT interval as assessed by the Fridericia's Correction Formula (QTcF).

  Day 1 Cycles 1 and 2 (each cycle is 21 days)

• Assess safety changes of body weight.

  If during treatment a subject's body weight changes by \>10%, the dose should be adjusted.

  Day 1 of each cycle (there are 34 cycles; 21 days for each cycle)

• Number of participants with dose limiting toxicities (DLTs)

  A DLT is defined as the occurrence of Grade 3/4 adverse events within the first cycle (the first 21 days) of treatment that are considered by the investigator to be at least possibly related to OBI-3424.

  Throughout Cycle 1 (21 days for each cycle)

• Define the Recommended Phase 2 Dose (RP2D)

  Determination of the MTD, based on the frequently of DLTs observed in Cycle 1 in subjects recruited to the Dose Escalation Phase.

  Days 1 and 8 of each cycle (all 34 cycles and there are 21 days for each cycle)

• Pharmacokinetics (PK) - Time to maximum concentration (Tmax)

  Tmax of OBI-3424 and OBI-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - Maximum peak plasma concentration (Cmax)

  Cmax of OBI-3424 and OBI-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - The magnitude of the slope of the linear regression of the log concentration vs. time profile during the terminal phase (Kel)

  Kel of OBI-3424 and OBI-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - Half-life (T1/2)

  T1/2 computed as ln (2)/Kel of OBI-3424 and OBI-2660 will be computed for each subject where possible.

  Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)

• PK - Area under the concentration-time curve (AUClast)

  AUClast from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn

  Days 1 and 8 of Cycle 1 (Cycle 1 is 21 days)

Study Arms (2)

Dose escalation phase

EXPERIMENTAL

OBI-3424 (1.0 mg/m\^2 to 14.0 mg/m\^2) will be administered by IV infusion on Days 1 and 8 of each 21-day cycle or Day 1 of each 21-day cycle to determine the MTD and RP2D with a classic 3+3 dose escalation design.

Drug: OBI-3424

Cohort expansion phase

EXPERIMENTAL

OBI-3424 (12 mg/m\^2) will be administered by IV infusion on Day 1 of each 21-day cycle.

Drug: OBI-3424

Interventions

OBI-3424 DRUG

liquid formulation for Intravenous infusion

Cohort expansion phase; Dose escalation phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
• Recovered from toxicities of prior therapy to Grade 0 or 1
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Acceptable liver function:
• Bilirubin ≤1.5 × institutional ULN
• AST and ALT ≤3.0 × ULN, or ≤5.0 × ULN for subjects with liver involvement
• Acceptable renal function:
• a. Creatinine clearance \>30 mL/min according to the Cockcroft-Gault formula
• Acceptable hematologic status (without hematologic support, other than red blood cell transfusion):
• ANC ≥1500 cells/μL
• Platelet count ≥100,000/μL
• Hemoglobin ≥9.0 g/dL (prior packed red blood cell transfusion or erythropoietin support is allowed).
• Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation.

You may not qualify if:

• Prior radiotherapy to more than 25% of the bone marrow
• Symptomatic brain metastases, unless previously treated and well controlled for at least 4 weeks after central nervous system (CNS)-directed treatment as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) during the Screening Period. Patients with known leptomeningeal disease are excluded.
• Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancers whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the current study
• Patients with hepatocellular carcinoma (applies to Expansion Phase only)
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Treatment with radiation therapy, surgery, chemotherapy, targeted therapies or hormones within 3 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)
• Concomitant use of strong CYP3A4 inhibitors/inducers
• Concomitant use of naproxen within a 48-hour window before and after OBI-3424 dosing
• Females who are pregnant or breast-feeding
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
• Unwillingness or inability to comply with the study protocol for any reason

Sponsors & Collaborators

• OBI Pharma, Inc: lead

Study Sites (5)

Scripps Clinic Torrey Pines

La Jolla, California, 92037, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Tsimberidou AM, Verschraegen CF, Wesolowski R, Shia CS, Hsu P, Pearce TE. Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors. Br J Cancer. 2023 Aug;129(2):266-274. doi: 10.1038/s41416-023-02280-4. Epub 2023 May 12.

  PMID: 37173365 DERIVED

Study Officials

• Apostolia Tsimberidou, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2018
• First Posted: July 19, 2018
• Study Start: July 2, 2018
• Primary Completion: February 13, 2024
• Study Completion: March 21, 2024
• Last Updated: October 15, 2024

Record last verified: 2024-04

Locations

US (5)