ProAgio in Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies

Inclusion Criteria:

For the Escalation Cohort:

• Histologic or cytologic diagnosis of a solid tumor malignancy for which no curativetherapy exists.

• Individuals must have evaluable disease, either by clinical exam, biochemicalmarkers (including but not limited to CA 19-9 serum tumor marker forpancreatobiliary cancer, or other appropriate tumor marker in other tumor types),and/or radiographic studies.

• Individuals must have received at least one prior systemic treatment for advanceddisease.

• For the Expansion Cohort:

• Histologic or cytologic diagnosis of non-neuroendocrine pancreatic cancer.Individuals with mixed acinar-neuroendocrine histology are eligible.

• All Participants must have measurable disease, per RECIST 1.1.

• All individuals must have advanced or recurrent disease and have received at leastone prior systemic treatment. Specifically:

• Individuals with metastatic, locally advanced/unresectable, or borderlineresectable pancreatic cancer at diagnosis, must have received at least oneprior systemic treatment and still be considered ineligible for potentiallycurative resection.

• Individuals who have undergone surgical resection and have tumor recurrencethat is not amenable to local therapy, are eligible if:

• Tumor recurs within six months of the completion of adjuvant therapy, OR

• Further standard of care therapy is not a viable option due to prior resistance orintolerance, or a medical contraindication to both FOLFIRINOX (or NALIRIFOX) andgemcitabine-based chemotherapy

• Individuals in the Biopsy Arm of the expansion cohort must have disease amenable tosafe biopsy and willingness to undergo the procedure.

• All individuals must be more than 14 days removed from most recent standard of careor experimental drug treatment for their tumor.

• Age ≥18 years. Because no dosing or adverse event data are currently available onthe use of ProAgio in individuals <18 years of age, children are excluded from thisstudy.

• ECOG performance status ≤ 2 (Karnofsky ≥>60%).

• Individuals must have adequate organ and marrow function as defined below:

• Aabsolute neutrophil count (ANC) ≥1,000/mcL

• hemoglobinHemoglobin (hgb) ≥9 g/ dL

• plateletsPlatelets ≥75,000/mcL

• Aspartate aminotransferase (AST)/ alanine transaminase (ALT) ( ≤ 2.5 x institutionalupper limit of normal (ULN). AST and ALT (up to 5x ULN) is permitted forparticipants individuals with liver metastases)

• Total bilirubin ≤1.5 X institutional ULN

• Creatinine within normal institutional limits OR

• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levelsabove institutional normal

• Serum albumin >2.5 mg/dL without intravenous supplementation

• Individuals must also have:

• Baseline QTcF interval of ≤ 470 ms

• Baseline resting heart rate > 45 beats per minute and <100 beats per minute

• Individuals of child-bearing potential (IOCBP) and individuals able to father achild men must agree to use an effective method of contraception as follows:

• IOCBP must agree to use an effective method of contraception (barrier, surgicalsterilization, abstinence) prior to study entry, for the duration of studyparticipation, and for at least 6 months after the last dose of study drug(s).

• Individuals able to father a child must agree to use an effective method ofcontraception (barrier, surgical sterilization, abstinence) for the duration of thestudy treatment and up to 6 months after the last dose of the study drug(s). We alsowill recommend individuals able to father a child with IOCBP partners to ask them tobe on an effective birth control (hormonal, intrauterine device [(IUD)], surgicalsterilization.

• Ability of individual to understand and the willingness to sign a written informedconsent document.

Exclusion Criteria:

• Diagnosis of primary malignant CNS tumor.

• Individuals who are receiving any other investigational agents.

• Evidence of significant, uncontrolled concomitant diseases which could affectcompliance with the protocol or interpretation of results, including but not limitedto significant pulmonary disease other than that related to the primary cancer,uncontrolled diabetes mellitus, unstable angina, significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease) and/orpsychiatric illness/social situations within 12 weeks that would limit compliancewith study requirements.

• Individuals with known diagnosis of a chronic neurologic disorders (such as multiplesclerosis, Huntington's disease, Parkinson's disease, or uncontrolled epilepsy)which causes motor disturbance, visual disturbance or seizure and could confoundassessment of neurologic toxicity caused by the study drug.

• Pregnant or nursing individuals are excluded from this study because ProAgio is anagent with the potential for teratogenic or abortifacient effects. Because there isan unknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with ProAgio, breastfeeding should be discontinued if themother is treated with ProAgio.

• Individuals with leptomeningeal disease or with CNS metastases that are untreated,have required steroid treatment within the last 4 weeks, or anti-convulsant therapyin the last 14 days. For dose escalation cohort only: Individuals with any known CNSmetastases are excluded. Those with symptoms suggestive of possible CNS metastases (such as new headaches) must undergo brain MRI as part of screening.

• Individuals who have undergone a recent minor surgical procedure (within <14 days)such as biliary stenting or major surgical procedure (within ≥ 28 days).

• Individuals who have undergone recent (within ≤ 14 days) external beam radiationtherapy are excluded. Individuals who have undergone recent (within ≤ 28 days)treatment with radioactive therapeutics (such as Y90 or radio-immune conjugates) areineligible.

• Individuals with uncontrolled bleeding episodes <28 days prior to enrollment areexcluded.

• Individuals with active or uncontrolled infections are excluded.

• Individuals with HIV and detectable viral load are excluded. Patents on appropriatehighly active anti-retroviral therapy with undetectable viral load are eligible.

• Individuals with a history of Hepatitis B or C are excluded unless there isdocumented evidence of effective treatment and/or cure with undetectable viral load.

• Individuals with recent (within < 28 days) thromboembolic disease including but notlimited to acute coronary syndrome, stroke, or transient ischemic attack, recentdeep vein thrombosis or pulmonary embolism.

• Individuals with thromboembolic disease including but not limited to acute coronarysyndrome, stroke, or transient ischemic attack, recent deep vein thrombosis orpulmonary embolism who have continued symptoms, or who are not on stable doses ofappropriate antiplatelet / anticoagulant regimens are excluded.