A Study of ELI-002 7P, With or Without Tislelizumab, in People With Pancreatic Cancer

Official title

A Pilot Study of Neoadjuvant mFOLFIRINOX and ELI002-7P Treatment With or Without Tislelizumab in Borderline and Resectable Pancreatic Ductal Adenocarcinoma

Overview

The researchers are doing this study to find out whether ELI-002 7P in combination with mFOLFIRINOX, with or without tislelizumab, is a safe treatment approach in people who have pancreatic ductal adenocarcinoma (PDAC) with a KRAS mutation. In addition, the researchers are doing this study to find out whether the study treatment is effective against PDAC.

Detailed description

This is an open-label, multi-institution pilot study of neoadjuvant mFOLFIRINOX (5-Fluorouracil, oxaliplatin, leucovorin, irinotecan) and a lipid-conjugated Kristin-Ras (KRAS) therapeutic cancer immunotherapy (ELI-002 7P vaccine), with or without Tislelizumab, in patients diagnosed with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC).

Interventions

• Drug ELI-002 7P
  a subcutaneous (SC) injection under the skin
• Drug Tislelizumab
  s an intravenous (IV) infusion
• Drug mFOLFIRINOX
  neoadjuvant mFOLFIRINOX (5-Fluorouracil,oxaliplatin, leucovorin, irinotecan)

Primary outcome measures

• the proportion of patients with a Grade 3 or higher drug-related adverse event (AE) [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

\- Documentation of Disease

• Pathologically confirmed adenocarcinoma of the pancreas.
• Presence of one of seven KRAS mutations: G12D, G12V, G12R, G12C, G12A, G12S, or G13D.

• Definition of Disease
• Patients must have resectable or borderline resectable localized disease as defined by NCCN Guidelines v2.2025. Staging CT or MRI of the chest/abdomen/pelvis at enrollment must be negative for metastatic disease.

• Prior Treatment
• Up to 4 doses of neoadjuvant mFOLFIRINOX are allowed prior to enrollment. Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade

1 (except for hypothyroidism requiring medication, which must have resolved to Grade ≤2), alopecia, and other toxicities considered clinically nonsignificant and/or stable on supportive therapy as determined by the investigator).

• Age ≥18 years.
• ECOG Performance Status 0-1
• Pregnancy and Nursing
• Not pregnant or breastfeeding.
• Evidence of post-menopausal status or a negative urinary or serum pregnancy test for females of child-bearing potential within 28 days prior to initiation of treatment.

• Required Organ Function
• Hematologic function:
• ANC ≥1,500/mm³
• Platelets ≥100,000/mm³
• Hemoglobin ≥8.0 g/dL

• Renal function:
• Creatinine clearance ≥50 mL/min (Cockcroft-Gault formula or 24-hour urine collection).

• Hepatic function:
• Total bilirubin ≤1.5 × ULN (Gilbert's syndrome allowed up to ≤3 × ULN)
• AST and ALT ≤3 × ULN Albumin: ≥2.5 g/dL

• Cardiac function: Patients with known cardiac disease or prior exposure to cardiotoxic agents should undergo risk assessment per NYHA classification; patients must be class or better. Compliance and Life Expectancy
• Patient is willing and able to comply with protocol procedures, treatment, and follow-up.
• Estimated life expectancy of at least 12 weeks per treating physician.

• Comorbid Conditions
• No active infection requiring parenteral antibiot ic(s)
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

• Allergies: No history of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent (s) (or any of its excipients).
• Concomitant Medications
• Concomitant medication use should only exclude patients when clinically relevant drug-drug interactions or overlapping toxicities are expected to impact safety or efficacy. All concomitant medications from 7 days prior to screening through 12 weeks after the last dose of investigational product must be documented in the medical record.

• Contraception Requirements
• Patients of reproductive potential must use highly effective contraception from screening through 90 days after the last dose of immunotherapy.

Exclusion criteria

• Locally advanced unresectable PDAC (per NCCN v2.2025), including unreconstructable venous anatomy, arterial tumor contact ≥180° (superior mesenteric, celiac, or hepatic artery), or aortic invasion
• Metastatic PDAC.
• Prior treatment with TNF receptor agonists (OX40, CD27, CD137/4-1BB, GITR) or prior checkpoint inhibitor therapy (anti-CTLA-4, anti-PD-1, anti-PD-L1).
• Active infection including tuberculosis, hepatitis A, active HBV (HBsAg+), or active HCV. Patients with resolved HBV (anti-HBc+, HBsAg-) may enroll. HCV Ab+ patients are eligible if HCV RNA PCR is negative. Successfully treated cholangitis is not exclusionary if no active infection remains.
• Known HIV infection not meeting the on-study guideline criteria above.
• Active or prior documented autoimmune/inflammatory disorders including: IBD, systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, systemic sclerosis, CNS or motor neuropathy of autoimmune origin (e.g., Guillain-Barré, myasthenia gravis, multiple sclerosis). Exceptions: vitiligo, alopecia, stable hypothyroidism on replacement, remote (>5 years) inactive autoimmune disease, or celiac disease controlled by diet.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic CHF, unstable angina, uncontrolled arrhythmia, uncontrolled hypertension, interstitial lung disease, serious GI conditions with chronic diarrhea, or psychiatric/social situations limiting compliance.
• Current or prior systemic immunosuppressive medication within 14 days of first ELI-002 7P dose.
• Exceptions: intranasal/inhaled/topical steroids, local steroid injections, physiologic replacement doses (≤10 mg prednisone/day or equivalent), steroids as premedication for imaging contrast allergy, or limited steroid use as anti-emetic with mFOLFIRINOX.
• Receipt of a live attenuated vaccine within 30 days prior to first dose of immunotherapy.
• Pregnancy, breastfeeding, or unwillingness to use effective contraception during treatment and for 90 days after last immunotherapy dose.
• Allergy or hypersensitivity to study drugs or excipients.
• Any other malignancy within 3 years except adequately treated cervical carcinoma in situ, non-muscle-invasive bladder cancer, localized prostate cancer, or non-melanoma skin cancers.
• Prior allogeneic organ transplantation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities) — Basking Ridge
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale
• Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities) — Commack
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison
• Memorial Sloan Kettering Cancer Center (All Protocol Activites) — New York
• Memorial Sloan Kettering Nassau (Limited Protocol Activites) — Rockville Centre

Identifiers

NCT: NCT07671339 · 25-386

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗