Solid TumorPhase 1/2NCT03592264

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

A Phase 1/2 study testing OBI-3424 in people with Solid Tumor and Pancreatic Adenocarcinoma, run by OBI Pharma, Inc at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Solid Tumor, Pancreatic Adenocarcinoma
What is being tested?: OBI-3424
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 68 participants
Where: 5 sitesUnited States
Study dates: 2 Jul 2018to 21 Mar 2024
Phase: Phase 1/2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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Bilirubin ≤1.5 × institutional ULN
AST and ALT ≤3.0 × ULN, or ≤5.0 × ULN for subjects with liver involvement
Acceptable renal function:
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.
Dose Escalation Phase Subjects Only (Inclusion Criteria):
Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Tumor progression after most recent therapy
Expansion Phase Subjects Only (Inclusion Criteria):
Available tumor tissue, either archival or fresh (fresh preferred).
For treatment, an AKR1C3 IHC H-score of ≥ 100 using a validated IHC assay in one of the following tumor types to be enrolled in the respective cohort:
Cohort A: Pancreatic Adenocarcinoma
Cohort B: Basket (any solid tumor type other than pancreatic adenocarcinoma)

Who cannot join

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

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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

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
MD Anderson Cancer Center
Houston, Texas, 77030
Scripps Clinic Torrey Pines
La Jolla, California, 92037
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903

Other trials in United States

About this study

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
Being tested: OBI-3424

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OBI-3424Drug
liquid formulation for Intravenous infusion

Study groups in NCT03592264
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: OBI-3424

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Days 1 and 8 of Cycle 1 (Cycle 1 is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Jul 201821 Mar 2024

First posted19 Jul 2018
Study start2 Jul 2018
Primary completion13 Feb 2024
Study completion21 Mar 2024

Why it stopped: Little evidence of clinical activity in tumor types enrolled

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Solid TumorStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 68 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03592264
Sponsor's protocol ID: OBI-3424-001
Status last verified: Apr 2024
First submitted: 21 May 2018
Last updated: 15 Oct 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Tsimberidou AM, Verschraegen C, Sigal D, Lenz HJ, Hochster H, Baysal MA, Chakraborty A, Lee I, Ristoski K, Xu D. Phase 2 dose-expansion trial of OBI-3424, a DNA-alkylating prodrug, in patients with advanced solid tumors expressing AKR1C3. Oncologist. 2026 Jul 8;31(8):oyag254. doi: 10.1093/oncolo/oyag254.
PubMed 42390142
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.
PubMed 37173365

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
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RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
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All Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study of OBI-3424 in Subjects with Advanced Solid Tumors
ClinicalTrials.gov ID: NCT03592264
Acronym / sponsor ID: OBI-3424-001
Conditions: Solid Tumor, Pancreatic Adenocarcinoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Little evidence of clinical activity in tumor types enrolled
Enrolment: 68 participants (actual)
Lead sponsor: OBI Pharma, IncIndustry (pharma, biotech, devices)
Study start: 2 Jul 2018 (actual)
Primary completion: 13 Feb 2024 (actual)
Study completion: 21 Mar 2024 (actual)
First posted: 19 Jul 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Dose escalation phase	Experimental	Drug: OBI-3424OBI-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	Experimental	Drug: OBI-3424OBI-3424 (12 mg/m^2) will be administered by IV infusion on Day 1 of each 21-day cycle.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

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

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OBI-3424liquid formulation for Intravenous infusion	Drug	Cohort expansion phase, Dose escalation phase

Primary outcome

Incidence and severity of adverse events (AEs)
Time frame: 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.
Assess safety changes in electrocardiogram (ECG)
Time frame: 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.
Time frame: 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.
Number of participants with dose limiting toxicities (DLTs)
Time frame: 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.
Define the Recommended Phase 2 Dose (RP2D)
Time frame: 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.
Pharmacokinetics (PK) - Time to maximum concentration (Tmax)
Time frame: 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 - Maximum peak plasma concentration (Cmax)
Time frame: 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)
Time frame: 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 - Half-life (T1/2)
Time frame: 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 - Area under the concentration-time curve (AUClast)
Time frame: 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

Results and safety

The study was stopped early (reason given: Little evidence of clinical activity in tumor types enrolled). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
Derived from this study: PubMed 42390142Tsimberidou AM, Verschraegen C, Sigal D, Lenz HJ, Hochster H, Baysal MA, Chakraborty A, Lee I, Ristoski K, Xu D. Phase 2 dose-expansion trial of OBI-3424, a DNA-alkylating prodrug, in patients with advanced solid tumors expressing AKR1C3. Oncologist. 2026 Jul 8;31(8):oyag254. doi: 10.1093/oncolo/oyag254.
Derived from this study: PubMed 37173365Tsimberidou 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.
Individual participant dataSharing planned: Undecided

Related trials for Solid Tumor

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Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
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Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Apostolia Tsimberidou, MD, PHD principal investigator

M.D. Anderson Cancer Center

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing OBI-3424 in people with Solid Tumor and Pancreatic Adenocarcinoma, run by OBI Pharma, Inc at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Little evidence of clinical activity in tumor types enrolled). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (AEs) (time frame: 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.). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03592264, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.