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.
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.
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).
Sequential
ONT01
DrugPer assigned dose level.
Gemcitabine
DrugThe dose of gemcitabine is 1000 mg/m\^2.
Nab paclitaxel
DrugThe dose of nab-paclitaxel is 125 mg/m\^2.
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).
Number of participants with dose-limiting toxicities (DLTs) (Phase I only)
DLTs are defined in the protocol.
Progression-free rate at 6 months (RP2D participants in Phase I and Phase II participants only)
Frequency of adverse events (RP2D participants in Phase I and Phase II participants in experimental arm only)
\- The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.
Objective response rate (ORR) (RP2D participants in Phase I and Phase II participants in experimental arm only)
* ORR is defined as the proportion of patients with disease control (Complete response + Partial response). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Progression-free survival (PFS) (RP2D participants in Phase I and Phase II participants in experimental arm only)
* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. * Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Overall survival (OS) (RP2D participants in Phase I and Phase II participants in experimental arm only)
OS is defined as the duration of time from start of treatment to time of death from any cause. The alive patients are censored at last follow-up date.
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Washington University School of Medicine
Lead sponsor
National Cancer Institute (NCI)
Collaborator
