Liposomal irinotecan and 5‑FU with a PD‑L1 blocker plus an anti‑angiogenic pill, with or without focused radiation, for second‑line metastatic pancreatic cancer

Efficacy and Safety of Second-line Therapy by Nal-IRI/5-FU/LV Chemotherapy Combined With PD-L1 Inhibitor and Multi-target Anti-angiogenic Small Molecule±SBRT in Metastatic Pancreatic Cancer Patients: a Prospective, Multicentre, Single-arm, Multi-cohort Study

This study will try combining liposomal irinotecan and 5‑FU with a PD‑L1 blocker and an oral anti‑angiogenic drug, with or without targeted radiation, in people whose metastatic pancreatic cancer has progressed after first‑line chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (other)
• Drugs / interventions: anlotinib, chemotherapy, bemosubaemab
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06662006 on ClinicalTrials.gov

What this trial studies

This is a single‑arm, prospective Phase 2 study planning to enroll about 56 patients with metastatic pancreatic cancer who progressed after first‑line therapy. All participants receive liposomal irinotecan (nal‑IRI) plus 5‑fluorouracil/leucovorin together with a PD‑L1 antibody (bemosubaemab) and the multi‑targeted anti‑angiogenic agent anlotinib; a second cohort also receives stereotactic body radiation therapy (SBRT). Treatment is given in repeated 3‑week cycles with irinotecan and 5‑FU on days 1 and 15, anlotinib orally on days 1–14, and PD‑L1 antibody every 3 weeks, and patients are followed for response, safety, and survival. Enrollment requires meeting prespecified laboratory and performance status criteria and signing informed consent.

Who should consider this trial

Good fit: Adults 18–75 with histologically or cytologically confirmed metastatic pancreatic cancer who progressed after first‑line therapy, have measurable disease, ECOG ≤2, adequate blood counts and organ function, and no prior fluorouracil or irinotecan exposure in first line are the intended participants.

Not a fit: Patients with ECOG >2, inadequate hematologic or organ function, no measurable metastatic lesions, or prior exposure to fluorouracil/irinotecan in first line are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could shrink tumors and potentially extend progression‑free or overall survival compared with existing second‑line options.

How similar studies have performed: Liposomal irinotecan plus 5‑FU/LV has demonstrated benefit as a second‑line regimen in prior trials, but combining it with PD‑L1 blockade and multi‑target anti‑angiogenic therapy (and adding SBRT) is a novel approach with limited published data.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years, ECOG score of ≤2 points, expected survival time ≥ 3 months.
2. Patients with histologically or cytologically confirmed advanced metastatic pancreatic cancer.
3. Imaging suggests distant measurable lesions.
4. Failure of first-line therapy and no use of fluorouracil, irinotecan, or liposomal irinotecan drugs in the first-line therapy.

Patients need to meet the following hematologic indicators e1. Neutrophil count ≥ 1.5×109/L e2. Hemoglobin ≥ 10 g/dL e3. Platelet count ≥ 100×109/L f. Patients need to meet the following biochemical parameters f1. Total bilirubin ≤ 1.5× upper limit of normal (ULN) f2. AST and ALT \<1.5×ULN f3. Creatinine clearance ≥ 60ml/min g. Patients of childbearing age need to take appropriate protective measures (contraception or other methods of birth control) before enrollment and during the trial.

H. Has signed an informed consent form. i. Able to follow the study protocol and follow-up process.

Exclusion Criteria:

1. Have received second-line or more anti-tumor therapy in the past.
2. First-line treatment with fluorouracil, irinotecan or liposomal irinotecan, etc.
3. Patient has a prior history of other tumors, unless it is cervical cancer in situ, treated squamous cell carcinoma or bladder epithelial tumors (Ta and TIS) or other malignancies that have received curative therapy (at least more than 5 years prior to enrollment).
4. Patient has an active bacterial or fungal infection (≥ 3rd edition NCI-CTC2 grade).

Patient has HIV, HCV, HBV infection, uncontrolled coronary artery disease or asthma, uncontrolled cerebrovascular disease or other disease deemed non-enrollable by the investigator.

f. Patients with autoimmune diseases or immunodeficiencies who should be treated with immunosuppressive drugs.

g. Pregnant and lactating women. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.

h. Substance abuse, clinical or psychological, or social factors that compromise informed consent or study conduct.

i. Those who may be allergic to treatment drugs.

Where this trial is running

Nanjing, Jiangsu

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Study coordinator: Juan Du, M.D. Ph.D

Conditions: Advanced Metastatic Pancreatic Cancer, pancreatic cancer, liposomal irinotecan, benmelstobart, anlotinib