ONT01 and Gemcitabine/Nab-paclitaxel as Second Line Therapy for Metastatic Pancreatic Ductal Adenocarcinoma
Phase I/II Clinical Trial of ONT01 and Gemcitabine/Nab-paclitaxel as Second Line Therapy for Metastatic Pancreatic Ductal Adenocarcinoma: Reprogramming Tumor-associated Myeloid Cells
2 other identifiers
interventional
61
1 country
1
Brief Summary
The investigators hypothesize that CD11b agonism reprograms the tumor microenvironment (TME) to overcome resistance to checkpoint immunotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, the investigators propose an open label phase I/II clinical trial of ONT01 with gemcitabine and nab-paclitaxel in unresectable pancreatic ductal adenocarcinoma prior to future studies incorporating anti-PD1 checkpoint immunotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2026
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 24, 2025
CompletedFirst Posted
Study publicly available on registry
April 1, 2025
CompletedStudy Start
First participant enrolled
March 25, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2029
March 30, 2026
March 1, 2026
2.5 years
March 24, 2025
March 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Recommended phase II dose (RP2D) (Phase I only)
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. In the absence of excess toxicity, the maximum tolerated dose will become the recommended phase 2 dose (RP2D).
After completion of cycle 1 (each cycle is 28 day) for all Phase I participants (estimated to be 12 months)
Number of participants with dose-limiting toxicities (DLTs) (Phase I only)
DLTs are defined in the protocol.
After completion of cycle 1 (each cycle is 28 day)
Progression-free rate at 6 months (RP2D participants in Phase I and Phase II participants only)
At 6 months from start of treatment
Secondary Outcomes (5)
Frequency of adverse events (RP2D participants in Phase I and Phase II participants in experimental arm only)
From start of treatment through 30 days after last dose of treatment (estimated to be 7 months)
Objective response rate (ORR) (RP2D participants in Phase I and Phase II participants in experimental arm only)
Through completion of treatment (estimated to be 6 months)
Progression-free survival (PFS) (RP2D participants in Phase I and Phase II participants in experimental arm only)
Through completion of follow-up (estimated to be 18 months)
Overall survival (OS) (RP2D participants in Phase I and Phase II participants in experimental arm only)
Through completion of follow-up (estimated to be 18 months)
Disease control rate (DCR) (RP2D participants in Phase I and Phase II participants in experimental arm only)
Through completion of follow-up (estimated to be 18 months)
Study Arms (3)
Phase I Dose de-escalation (starting dose): ONT01 + Gemcitabine + Nab-paclitaxel
EXPERIMENTALONT01 is an oral medication taken twice daily on Days 1-21 of each 28-day cycle. The starting dose is 800 mg. Gemcitabine and nab-paclitaxel will be given as per standard of care (intravenous on Days 1, 8, and 15 of each 28-day cycle).
Phase 2 Experimental Arm: ONT01 + Gemcitabine + Nab-paclitaxel
EXPERIMENTALONT01 is an oral medication taken twice daily on Days 1-21 of each 28-day cycle. The dose will determined during the Phase I portion of the trial. Gemcitabine and nab-paclitaxel will be given as per standard of care (intravenous on Days 1, 8, and 15 of each 28-day cycle).
Phase 2 Control Arm: Gemcitabine + Nab-paclitaxel
ACTIVE COMPARATORGemcitabine and nab-paclitaxel will be given as per standard of care (intravenous on Days 1, 8, and 15 of each 28-day cycle).
Interventions
Per assigned dose level.
The dose of gemcitabine is 1000 mg/m\^2.
The dose of nab-paclitaxel is 125 mg/m\^2.
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed adenocarcinoma of the pancreas.
- Measurable or evaluable disease per RECIST 1.1.
- Previously treated with first-line systemic therapy for unresectable/advanced or metastatic PDAC and experienced progression or became intolerant to the therapy and is in need of another line of systemic therapy in the opinion of the investigator.
- At least 18 years of age.
- ECOG performance status ≤ 1.
- Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN
- Creatinine ≤ 1.5 x IULN or Creatinine clearance \> 50 mL/min by Cockcroft-Gault
- The effects of ONT01 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 120 days after last dose of ONT01 or 180 days after last dose of nab-paclitaxel/gemcitabine. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
You may not qualify if:
- Received more than one line of treatment or received gemcitabine or nab-paclitaxel in the metastatic setting. Prior therapy in the adjuvant or neoadjuvant therapy will count as a line of treatment if progression occurred less than 6 months after the last dose of systemic therapy. The following exception applies:
- If treated in the adjuvant or neoadjuvant setting with systemic therapy and progression occurred greater than 6 months after last dose, the adjuvant or neoadjuvant systemic therapy may have included gemcitabine or nab-paclitaxel. If progression occurred within 6 months of the last dose of systemic therapy in the adjuvant or neoadjuvant setting, then that therapy must not have included gemcitabine or nab-paclitaxel.
- Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment.
- Major surgery (defined as surgery that requires general anesthesia) within 28 days of C1D1 of ONT01 (phase I portion) or date of randomization (phase II portion).
- Chemotherapy, small molecular directed therapy, immunotherapy, and/or radiation therapy within 14 days of C1 of ONT01 (phase I portion) or date of randomization (phase II portion).
- History of other malignancy with the exception of 1) malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease and 2) known indolent malignancies that do not require treatment and will likely not alter the course of treatment of metastatic PDAC.
- History of allogeneic organ or stem cell transplant.
- Currently receiving any other investigational agents.
- Patients with known, untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ONT01, gemcitabine, nab-paclitaxel, or other agents used in the study.
- Average QTc \>470 msec on screening EKGs.
- Gastrointestinal condition which could prevent absorption of ONT01, or inability to digest ONT01.
- Clinically significant peripheral neuropathy grade 2 or worse.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test within 7 days of C1D1 (phase I portion) or date of randomization (phase II portion).
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Patrick Grierson, M.D., Ph.D.
Washington University School of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 24, 2025
First Posted
April 1, 2025
Study Start
March 25, 2026
Primary Completion (Estimated)
September 30, 2028
Study Completion (Estimated)
September 30, 2029
Last Updated
March 30, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share