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

Phase 1

Terminated

• Conditions: Solid Tumor; Pancreatic Adenocarcinoma
• Interventions: Drug: OBI-3424

• Registration Number: NCT03592264
• Lead Sponsor: OBI Pharma, Inc

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-21
• Study Start: 2018-07-02
• Study First Submitted QC: 2018-07-09
• Study First Posted: 2018-07-19
• Primary Completion: 2024-02-13
• Study Completion: 2024-03-21
• Status Verified: 2024-04
• Last Update Submitted: 2024-10-11
• Last Update Posted: 2024-10-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

Not provided

Exclusion Criteria

1. Prior radiotherapy to more than 25% of the bone marrow
2. 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.
3. 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
4. Patients with hepatocellular carcinoma (applies to Expansion Phase only)
5. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
6. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
7. Treatment with radiation therapy, surgery, chemotherapy, targeted therapies or hormones within 3 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)
8. Concomitant use of strong CYP3A4 inhibitors/inducers
9. Concomitant use of naproxen within a 48-hour window before and after OBI-3424 dosing
10. Females who are pregnant or breast-feeding
11. 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
12. Unwillingness or inability to comply with the study protocol for any reason

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose escalation phase	OBI-3424	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.
Cohort expansion phase	OBI-3424	OBI-3424 (12 mg/m\^2) will be administered by IV infusion on Day 1 of each 21-day cycle.

Primary Outcome Measures

Name	Time	Method
Assess safety changes in electrocardiogram (ECG)	Day 1 Cycles 1 and 2 (each cycle is 21 days)	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).
Assess safety changes of body weight.	Day 1 of each cycle (there are 34 cycles; 21 days for each cycle)	If during treatment a subject's body weight changes by \>10%, the dose should be adjusted.
Define the Recommended Phase 2 Dose (RP2D)	Days 1 and 8 of each cycle (all 34 cycles and there are 21 days for each cycle)	Determination of the MTD, based on the frequently of DLTs observed in Cycle 1 in subjects recruited to the Dose Escalation Phase.
Incidence and severity of adverse events (AEs)	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.	Adverse events will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Number of participants with dose limiting toxicities (DLTs)	Throughout Cycle 1 (21 days for each cycle)	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.
Pharmacokinetics (PK) - Time to maximum concentration (Tmax)	Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)	Tmax of OBI-3424 and OBI-2660 will be computed for each subject where possible.
PK - Half-life (T1/2)	Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)	T1/2 computed as ln (2)/Kel of OBI-3424 and OBI-2660 will be computed for each subject where possible.
PK - Maximum peak plasma concentration (Cmax)	Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)	Cmax of OBI-3424 and OBI-2660 will be computed for each subject where possible.
PK - The magnitude of the slope of the linear regression of the log concentration vs. time profile during the terminal phase (Kel)	Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)	Kel of OBI-3424 and OBI-2660 will be computed for each subject where possible.
PK - Area under the concentration-time curve (AUClast)	Days 1 and 8 of Cycle 1 (Cycle 1 is 21 days)	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

Trial Locations

Locations (5)

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Scripps Clinic Torrey Pines; 🇺🇸 La Jolla, California, United States

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States