Maintenance combinatorial myeloid immunotherapy with odetiglucan and mitazalimab for unresectable pancreatic cancer

IGNITE: A Phase 2 Study of Maintenance Combinatorial Myeloid Immunotherapy in Patients With Unresectable Pancreatic Ductal Adenocarcinoma

This study will try a combination immunotherapy (odetiglucan plus mitazalimab) as maintenance treatment for adults with unresectable pancreatic cancer whose disease has not progressed after 4–6 months of first-line chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (other)
• Drugs / interventions: chemotherapy, prednisone, immunotherapy, mitazalimab
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT07199764 on ClinicalTrials.gov

What this trial studies

This is a Phase II, open-label, single-arm trial that gives odetiglucan and mitazalimab as maintenance therapy to patients with unresectable or metastatic pancreatic ductal adenocarcinoma who achieved at least stable disease or a partial response after 16–24 weeks of first-line chemotherapy. The protocol begins with a safety run-in evaluating dose-limiting toxicities over the first 21 days (Cycle 1) using an initial cohort of three patients at the recommended Phase II dose, with expansion to six if DLTs occur. After the run-in, the study enrolls three treatment cohorts (metastatic PR, metastatic SD, and locally advanced PR/SD) plus an observational cohort of roughly 50–60 patients divided to match those eligibility groups. Imaging-confirmed disease stability or partial response at the end of first-line treatment is required, and participants receive scheduled clinical and imaging follow-up to monitor safety and disease control.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable or metastatic pancreatic ductal adenocarcinoma who achieved at least stable disease or a partial response after 16–24 weeks of first-line chemotherapy and have no evidence of progression are ideal candidates.

Not a fit: Patients whose cancer progressed during first-line chemotherapy, those who are candidates for surgical resection, or those who cannot tolerate immunotherapy are unlikely to benefit from this maintenance approach.

Why it matters

Potential benefit: If successful, the combination could extend the period of disease control after first-line chemotherapy and potentially delay progression, which may improve survival and quality of life.

How similar studies have performed: Early-phase trials of CD40 agonists, alone or combined with other agents, have shown immune activation and some clinical responses in pancreatic cancer, but consistent survival benefits have not yet been established.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years old
* Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent
* Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma that is either locally advanced and unresectable, or metastatic
* Have received a minimum of 16 and no more than 24 weeks of a first line chemotherapy-based standard of care regimen, resulting in either a PR or SD with no evidence 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 24 weeks) is sufficient; confirmation is not required. If chemotherapy was discontinued between 16-24 weeks due to legitimate medical reasons (as determined by the investigator), the patient may still be eligible if they demonstrated SD or PR prior to discontinuation.
* Have resolution of all chemotherapy-related toxicities to pre-treatment levels with exception 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 biopsies are mandatory for all patients with accessible disease, unless determined to be medically infeasible by the investigator.
* Adequate organ function confirmed by the following laboratory values obtained ≤14 days 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 x upper limit of normal (ULN); if liver metastases, then ≤5 x ULN
  * Total bilirubin ≤1.5 x ULN; if liver metastases or metabolic disorder such as Gilbert's syndrome, then ≤2.5 x ULN
  * Estimated glomerular filtration rate (GFR) (CLCr) ≥45 mL/min using Cockcroft Gault formula
* Females of childbearing potential \[defined as a sexually mature woman who (1) has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time during the preceding 24 consecutive months)\] 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 study treatment.
  * Commit to complete abstinence from heterosexual contact or agree to use medical doctor-approved contraception throughout the study without interruption while receiving study treatment and for at least 120 days following last dose of study treatment.
* Males must practice complete abstinence or agree to use a condom (even if he has undergone a successful vasectomy) during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions 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 the treatment of cancer
* Prior exposure to odetiglucan
* Received any systemic treatment for pancreatic adenocarcinoma within 14 days prior to the first dose of study therapy. For investigational agents, patients must not have had treatment within a time interval less than at least 5 half-lives of the investigational agent prior to the first scheduled day of dosing in this study
* Had any active or inactive autoimmune disease or syndrome that required systemic treatment in the past 2 years, or currently requires systemic therapy with disease-modifying agents, corticosteroids, or immunosuppressive drugs. Examples include but are not limit to: rheumatoid arthritis, systemic sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g. Granulomatosis with polyangiitis, formerly Wegener's Granulomatosis), multiple sclerosis, 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 childhood asthma/atopy, hypothyroidism stable on hormone replacement, controlled asthma, psoriasis not requiring systemic treatment, Type I diabetes, Graves' disease, or Hashimoto's disease, or with medical monitor approval.
* An ongoing or active infection requiring intravenous antibiotics, antivirals, or antifungals during the 14 days prior to first dose of study drug
* An uncontrolled concurrent illness, symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, or cardiac 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 for males and \>460 msec for females
* A history of myocardial infarction within 6 months or a history of arterial thromboembolic 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 virus deoxyribonucleic acid (DNA) and negative for HB surface antigen
  * Patients with resolved or treated hepatitis C virus (HCV) (i.e. HCV antibody positive but undetectable HCV RNA)
* Received concurrent or prior use of an immunosuppressive agent within 14 days of the first dose of investigational agent, with the following exceptions and notes:

  * Systemic steroids at physiologic doses (equivalent to dose of 10 mg oral prednisone) are permitted
  * Intranasal, inhaled, topical intra-articular, and ocular corticosteroids with minimal 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-study related minor surgical procedures requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration. In all cases, patients must be sufficiently recovered and stable before treatment administration
* Other malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancer; or any other cancer from which the patient has been disease-free for at least 3 years
* Received a live vaccine within 28 days before the first dose of study drug. If enrolled, patients should not receive live vaccines during the study or for 28 days after the last dose of study treatment (Note: seasonal influenza vaccines for injection are generally inactivated and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed)
* Females who are pregnant or lactating or who intend to become pregnant during participation in the study are not eligible to participate
* Known alcohol or drug abuse
* Any clinically significant psychiatric, social, or medical condition that, in the opinion of the investigator, could increase the patient's risk, interfere with protocol adherence, or affect the patient's ability to give informed consent

Where this trial is running

Philadelphia, Pennsylvania

• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Study coordinator: Abramson Cancer Center Clinical Trials Service

Conditions: Pancreatic Ductal Adenocarcinoma