Clinical Study of Radiotherapy Combined With Adebrelimab and NALIRIFOX for Conversion Therapy in Locally Advanced Pancreatic Cancer

This study intends to explore conversion therapy for locally advanced pancreatic cancer (LAPC). The intervention starts with modified stereotactic body radiation therapy (3-day regimen), followed by systemic therapy within 1-2 weeks after irradiation. Subsequently, the investigator will evaluate the resectability of the lesion.

For subjects converted to resectable status, surgical resection will be performed, followed by postoperative adjuvant therapy.

For subjects who remain unresectable but maintain stable disease, a second cycle of conversion therapy will be continued. If the lesion is converted to resectable, surgical resection will be performed followed by adjuvant therapy. If disease progression occurs, subsequent treatment will be carried out in accordance with the first-line treatment for advanced pancreatic cancer.

For subjects who experience disease progression or distant metastasis, subsequent treatment will be administered by adjusting the chemotherapy regimen in accordance with the first-line standard regimen for advanced pancreatic cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma (PDAC)
• Intervention / Treatment: Drug: Adebrelimab (PD-L1 inhibitor); Drug: NALIRIFOX; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent form

Age 18-75 years

Histologically or cytologically confirmed pancreatic ductal adenocarcinoma

Locally advanced disease as determined by the investigator (with reference to the CSCO Clinical Practice Guidelines for Pancreatic Cancer)

No prior treatment for pancreatic cancer, including radiotherapy, chemotherapy, or surgery

At least one measurable lesion according to RECIST v1.1 criteria

ECOG performance status score of 0-1

Adequate organ function based on laboratory tests performed within 28 days prior to the first dose:

1. Complete blood count:

   Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 75 × 10⁹/L Hemoglobin ≥ 90 g/L

2. Blood biochemistry:

   Serum albumin ≥ 30 g/L Serum total bilirubin ≤ 1.5 × ULN ALT and AST ≤ 3 × ULN Serum creatinine (Cr) ≤ 1.5 × ULN; or creatinine clearance calculated by the Cockcroft-Gault formula > 50 mL/min

3. International normalized ratio (INR) ≤ 1.2, or prothrombin time (PT) exceeding the normal range by ≤ 2 seconds
4. Urine protein < 2+ (if urine protein ≥ 2+, 24-hour urine protein quantification is required; patients with 24-hour urine protein < 1.0 g are eligible) Male subjects and female subjects of childbearing potential must use contraceptive measures from the first dose until 6 months after the last dose of the study drug

Exclusion Criteria:

• Presence of distant metastasis

Contraindications to surgical resection of pancreatic cancer

History of another malignancy other than pancreatic cancer within 5 years prior to enrollment, or concurrent malignancy at the time of enrollment

Prior allogeneic stem cell transplantation or solid organ transplantation

Symptomatic active central nervous system (CNS) metastases and/or carcinomatous meningitis, or uncontrolled major seizure disorder, unless ruled out by CT or MRI

History of uncorrectable electrolyte disturbances, including serum potassium, calcium, or magnesium abnormalities

Current interstitial pneumonia or interstitial lung disease, history of interstitial pneumonia or interstitial lung disease requiring corticosteroid therapy, or any other condition that may interfere with the assessment and management of immune-related pulmonary toxicity; active pulmonary tuberculosis

Active autoimmune disease or history of autoimmune disease with potential for recurrence

Use of immunosuppressive agents or systemic corticosteroids for the purpose of immunosuppression within 2 weeks prior to enrollment

Active infection, unexplained fever ≥ 38.5°C within 1 week prior to enrollment, or baseline white blood cell count > 15 × 10⁹/L; use of oral or intravenous therapeutic antibiotics within 2 weeks prior to enrollment

Congenital or acquired immunodeficiency (e.g., HIV infection)

Receipt of a live attenuated vaccine within 4 weeks prior to enrollment, or anticipated need for such vaccination during adebrelimab treatment or within 60 days after the last dose

Clinically significant bleeding symptoms or evident bleeding tendency within 6 months prior to enrollment; known hereditary or acquired bleeding tendency or thrombotic tendency

Major vascular disease, arterial thromboembolism

Uncontrolled or poorly controlled cardiac clinical symptoms or disease, such as:

1. New York Heart Association (NYHA) Class > II heart failure, or left ventricular ejection fraction (LVEF) < 50% as assessed by color Doppler echocardiography
2. Unstable angina pectoris
3. Myocardial infarction within 1 year prior to initiation of study treatment
4. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention
5. QTc interval > 450 ms (males) or > 470 ms (females) (QTc calculated using Fridericia's formula; if the QTc value is abnormal, measurements should be repeated three times at 2-minute intervals and the average value taken) Uncontrolled pleural effusion, pericardial effusion, or moderate or greater ascites

Hypertension not adequately controlled with antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); history of hypertensive crisis or hypertensive encephalopathy

Presence of severe, non-healing or dehisced wounds, active ulcers, or untreated fractures

Major surgery (excluding diagnostic surgery) within 4 weeks prior to enrollment, or planned major surgery during the study period

History of intestinal obstruction and/or clinical symptoms or signs of gastrointestinal obstruction within 6 months prior to enrollment

Known allergy or hypersensitivity to any study drug or excipient

Participation in another clinical study of an investigational drug within 4 weeks prior to enrollment

Pregnant or breastfeeding women

Other factors that, in the opinion of the investigator, render the subject unsuitable for study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LPAC+NALIRIFOX+Adebrelimab; The intervention starts with modified stereotactic body radiation therapy (3-day regimen), followed by systemic therapy within 1-2 weeks after irradiation. Subsequently, the investigator will evaluate the resectability of the lesion. For subjects converted to resectable status, surgical resection will be performed, followed by postoperative adjuvant therapy. For subjects who remain unresectable but maintain stable disease, a second cycle of conversion therapy will be continued. If the lesion is converted to resectable, surgical resection will be performed followed by adjuvant therapy. If disease progression occurs, subsequent treatment will be carried out in accordance with the first-line treatment for advanced pancreatic cancer. For subjects who experience disease progression or distant metastasis, subsequent treatment will be administered by adjusting the chemotherapy regimen in accordance with the first-line standard regimen for advanced pancreatic cancer.

Drug: Adebrelimab (PD-L1 inhibitor); 20 mg/kg, intravenous infusion, administered on Day 1, every 3 weeks as one cycle (Q3W); Other Names: Adebrelimab; Drug: NALIRIFOX; Oxaliplatin: 60 mg/m², intravenous infusion over 2 hours, administered on Day 1 Irinotecan Liposome: 50 mg/m², intravenous infusion for more than 90 minutes, administered on Day 1 LV (Leucovorin): 400 mg/m², intravenous infusion over 2 hours, administered on Day 1 5-FU (5-Fluorouracil): 2400 mg/m², continuous intravenous infusion for 46 hours Every 3 weeks is defined as one treatment cycle (Q3W); Radiation: SBRT; Target Volume Delineation: The gross tumor volume GTV1 is delineated on CT images. A 1 cm inward contraction from GTV1 is performed to generate GTV-lattice, within which small spherical volumes GTV-sbrt with a diameter of 1-1.5 cm are created, and the spacing between adjacent spheres is 3 times the sphere diameter. Prescription Fractionation: Simultaneous integrated boost radiotherapy is adopted, with the prescription dose: GTV-sbrt: 24 Gy in 3 fractions; GTV1: 9 Gy in 3 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
surgical conversion rate	The proportion of patients who become eligible for surgery after treatment, relative to the total number of patients.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0/R1 Resection Rate	The proportion of patients who achieve R0 (microscopically margin-negative) or R1 (microscopically margin-positive) resection among all patients who undergo surgery. R0 is defined as no residual tumor at the resection margin; R1 is defined as microscopic residual tumor at the resection margin.	in 3 years
pCR	Pathological Complete Response: The absence of residual invasive tumor cells in the resected primary tumor specimen and/or lymph nodes upon pathological evaluation.	in 3 years
MPR	Major Pathological Response: The presence of ≤10% viable residual tumor cells in the resected primary tumor specimen upon pathological evaluation.	in 3 years
ORR	The proportion of patients who achieve a best overall response of either complete response (CR) or partial response (PR) as assessed by RECIST v1.1 (or other specified criteria) from the start of treatment until disease progression or initiation of subsequent anticancer therapy.	in 3 years
EFS	The time from the date of treatment initiation to the date of first occurrence of any of the following events: disease progression that precludes surgery, local or distant recurrence, or death from any cause. Patients who are event-free at the time of data cutoff are censored at the date of their last disease assessmen	in 3 years
OS	The time from the date of treatment initiation to the date of death from any cause. Patients who are alive at the time of data cutoff are censored at the date of last known follow-up.	in 3 years
the incidence, severity, and relationship to study treatment of adverse events (AEs) and serious adverse events (SAEs)	Safety endpoints include the incidence, severity, and relationship to study treatment of adverse events (AEs) and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	in 3 years
Immune Age Rejuvenation	Defined as a reduction in immune age of ≥3 years compared to the baseline measurement, as calculated by the immune age estimation model based on the data generated from the specified assay kit.	in 3 years

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 27, 2026
• First Submitted That Met QC Criteria: September 17, 2026
• First Posted (Actual): September 18, 2026

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: September 17, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors
• Other Study ID Numbers: IIT2026-249

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No