Maintenance Combinatorial Myeloid Immunotherapy for Unresectable Pancreatic Cancer

Inclusion Criteria:

• Age ≥ 18 years old

• Patients must be able to understand the study procedures and agree to participate inthe study by providing written informed consent

• Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinomathat is either locally advanced and unresectable, or metastatic

• Have received a minimum of 16 and no more than 24 weeks of a first linechemotherapy-based standard of care regimen, resulting in either a PR or SD with noevidence of progression within 14 days prior to first dose of study treatment. o Note: Patients must demonstrate at least stable disease (SD) or partial response (PR) by imaging. A single assessment showing PR at the end of chemotherapy (up to 24weeks) is sufficient; confirmation is not required. If chemotherapy was discontinuedbetween 16-24 weeks due to legitimate medical reasons (as determined by theinvestigator), the patient may still be eligible if they demonstrated SD or PR priorto discontinuation.

• Have resolution of all chemotherapy-related toxicities to pre-treatment levels withexception of alopecia (which can be ongoing) and neuropathy (which can be ≤ Grade 2).

• Eastern Cooperative Oncology (ECOG) performance status of 0 to 1.

• Measurable disease per RECIST v1.1 (Section 17.2) is a requirement for study entry.

• Willingness to undergo pre-treatment and on-treatment tumor biopsies. Tumor biopsiesare mandatory for all patients with accessible disease, unless determined to bemedically infeasible by the investigator.

• Adequate organ function confirmed by the following laboratory values obtained ≤14days prior to first administration of study treatment on Day 1:

• Absolute neutrophil count (ANC) ≥1.5 x 109/L

• Platelets ≥100 x 109/L

• Hemoglobin ≥9 g/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 xupper limit of normal (ULN); if liver metastases, then ≤5 x ULN

• Total bilirubin ≤1.5 x ULN; if liver metastases or metabolic disorder such asGilbert's syndrome, then ≤2.5 x ULN

• Estimated glomerular filtration rate (GFR) (CLCr) ≥45 mL/min using CockcroftGault formula

• Females of childbearing potential [defined as a sexually mature woman who (1) hasnot undergone hysterectomy (the surgical removal of the uterus) or bilateraloophorectomy (the surgical removal of both ovaries) or (2) has not been naturallypostmenopausal for at least 24 consecutive months (i.e. has had menses at any timeduring the preceding 24 consecutive months)] must:

• Have a negative serum or urine pregnancy test (β-human chorionic gonadotropin, β-hCG) as verified by the study investigator within 14 days prior to studytreatment.

• Commit to complete abstinence from heterosexual contact or agree to use medicaldoctor-approved contraception throughout the study without interruption whilereceiving study treatment and for at least 120 days following last dose ofstudy treatment.

• Males must practice complete abstinence or agree to use a condom (even if he hasundergone a successful vasectomy) during sexual contact with a pregnant female or afemale of childbearing potential while participating in the study, during doseinterruptions and for at least 120 days following last dose of study treatment.

Exclusion Criteria:

• Prior exposure to CD40 antibodies or any other immunomodulatory agent for thetreatment of cancer

• Prior exposure to odetiglucan

• Received any systemic treatment for pancreatic adenocarcinoma within 14 days priorto the first dose of study therapy. For investigational agents, patients must nothave had treatment within a time interval less than at least 5 half-lives of theinvestigational agent prior to the first scheduled day of dosing in this study

• Had any active or inactive autoimmune disease or syndrome that required systemictreatment in the past 2 years, or currently requires systemic therapy withdisease-modifying agents, corticosteroids, or immunosuppressive drugs. Examplesinclude but are not limit to: rheumatoid arthritis, systemic sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g.Granulomatosis with polyangiitis, formerly Wegener's Granulomatosis), multiplesclerosis, inflammatory bowel disease, or motor neuropathies of autoimmune origin (e.g. Guillain-Barre Syndrome) o Note: Patients are permitted to enroll if they have vitiligo or resolved childhoodasthma/atopy, hypothyroidism stable on hormone replacement, controlled asthma,psoriasis not requiring systemic treatment, Type I diabetes, Graves' disease, orHashimoto's disease, or with medical monitor approval.

• An ongoing or active infection requiring intravenous antibiotics, antivirals, orantifungals during the 14 days prior to first dose of study drug

• An uncontrolled concurrent illness, symptomatic congestive heart failure (New YorkHeart Association class III or IV), unstable angina, uncontrolled hypertension, orcardiac arrhythmia

• History of (non-infectious) pneumonitis that required steroids, current pneumonitis,or a history of interstitial lung disease

• QT interval corrected for heart rate using Fridericia's (QTcF) method >450 msec formales and >460 msec for females

• A history of myocardial infarction within 6 months or a history of arterialthromboembolic event within 3 months of the first dose of investigational agent

• A history of human immunodeficiency virus (HIV), hepatitis B (HB), or hepatitis C,except for the following:

• Patients with anti-HB core antibody but with undetectable HB virusdeoxyribonucleic acid (DNA) and negative for HB surface antigen

• Patients with resolved or treated hepatitis C virus (HCV) (i.e. HCV antibodypositive but undetectable HCV RNA)

• Received concurrent or prior use of an immunosuppressive agent within 14 days of thefirst dose of investigational agent, with the following exceptions and notes:

• Systemic steroids at physiologic doses (equivalent to dose of 10 mg oralprednisone) are permitted

• Intranasal, inhaled, topical intra-articular, and ocular corticosteroids withminimal systemic absorption are permitted

• Patients must not have known, symptomatic brain or leptomeningeal metastases

• Major surgical procedure within 21 days prior to first dose of study drug. Non-studyrelated minor surgical procedures requiring local/epidural anesthesia must becompleted at least 72 hours before study drug administration. In all cases, patientsmust be sufficiently recovered and stable before treatment administration

• Other malignancy, except for adequately treated basal or squamous cell skin canceror in situ cancer; or any other cancer from which the patient has been disease-freefor at least 3 years

• Received a live vaccine within 28 days before the first dose of study drug. Ifenrolled, patients should not receive live vaccines during the study or for 28 daysafter the last dose of study treatment (Note: seasonal influenza vaccines forinjection are generally inactivated and are allowed; however, intranasal influenzavaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed)

• Females who are pregnant or lactating or who intend to become pregnant duringparticipation in the study are not eligible to participate

• Known alcohol or drug abuse

• Any clinically significant psychiatric, social, or medical condition that, in theopinion of the investigator, could increase the patient's risk, interfere withprotocol adherence, or affect the patient's ability to give informed consent