NALIRIFOX+Adebrelimab+PULSAR for Advanced Pancreatic Cancer

NCT07595172 | Recruiting Phase 1 DMC

• 1 other identifier: PRIM-P1
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the safety and preliminary efficacy of NALIRIFOX combined with adebrelimab and PULSAR as first-line treatment for locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC). Additionally, it will explore potential predictive and efficacy-related biomarkers.

Conditions

Pancreatic Ductal Adenocarcinoma (PDAC); Locally Advanced and Metastatic Pancreatic Cancer

Keywords

chemotherapy; immunotherapy; radiotherapy; PDAC

Outcome Measures

Primary Outcomes (1)

• Objective response rate (RECIST v1.1)

  From the first patient enrollment until 6 months after the last patient enrollment

Secondary Outcomes (3)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  From the first patient enrollment until 6 months after the last patient enrollment

• Progression free survival

  From the first patient enrollment until 6 months after the last patient enrollment

• Overall survival

  From the first patient enrollment until 6 months after the last patient enrollment

Study Arms (1)

NALIRIFOX+Adebrelimab+PULSAR

EXPERIMENTAL

Drug: NALIRIFOX+Adebrelimab; Radiation: PULSAR

Interventions

NALIRIFOX+Adebrelimab DRUG

NALIRIFOX chemotherapy and Adebrelimab Injection

Also known as: chemotherapy and immunotherapy

NALIRIFOX+Adebrelimab+PULSAR

PULSAR RADIATION

PULSAR

Also known as: Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy

NALIRIFOX+Adebrelimab+PULSAR

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-75 years, regardless of gender.
• Histologically confirmed pancreatic ductal adenocarcinoma (PDAC).
• Previously untreated, locally advanced unresectable or metastatic PDAC, with at least one measurable lesion (RECIST v1.1) not previously irradiated.
• ECOG Performance Status (PS): 0-1.
• Expected survival ≥ 3 months.
• Willing and able to comply with study procedures, treatment, and follow-up.
• No contraindications to radiotherapy.
• Adequate organ function: WBC ≥ 2.5×10⁹/L, ANC ≥ 1.5×10⁹/L; Platelets ≥ 75×10⁹/L; Hemoglobin (HGB) ≥ 90 g/L (no transfusion or EPO dependence within 7 days); Total bilirubin (Tbil) ≤ 1.5×ULN; ALT/AST ≤ 5×ULN;Albumin ≥ 30 g/L; INR ≤ 1.5×ULN; Serum creatinine (Cr) ≤ 1.5×ULN Urine protein ≤ 1+
• HBsAg-positive patients must have HBV-DNA ≤ 1×10³ IU/mL (copies/mL). If HBV-DNA ≥ 1×10³ IU/mL, patients may still be eligible if chronic HBV is stable and not expected to increase risk, per investigator assessment.
• Voluntary participation with signed informed consent form.

You may not qualify if:

• History of severe hypersensitivity to chimeric, human(ized) antibodies, or fusion proteins.
• Pregnant or breastfeeding women, or men/women of childbearing potential unwilling/unable to use effective contraception during the study.
• Other malignancies within 5 years, except: Malignancies treated with curative intent and no known active disease for ≥5 years with low recurrence risk; Adequately treated non-melanoma skin cancer or lentigo maligna without disease evidence; Adequately treated carcinoma in situ (e.g., cervical, breast) with no current disease.
• Symptomatic moderate/severe pleural effusion or ascites.
• Active bleeding or coagulopathy (PT \>16s, APTT \>43s, INR \>1.5×ULN), bleeding tendency, or current use of thrombolytics/anticoagulants/antiplatelets.
• GI bleeding within 6 months or high bleeding risk (e.g., active ulcer with occult blood++). If occult blood+ persists, endoscopy required.
• High-risk esophageal/gastric varices needing intervention.
• History of drug abuse, psychiatric disorder, or inability to abstain.
• Solid organ/bone marrow transplant, or active autoimmune disease requiring systemic treatment within 2 years.
• Immunodeficiency or HIV infection.
• Objective evidence of pulmonary fibrosis, interstitial lung disease, pneumoconiosis, radiation-/drug-induced pneumonitis, or severely impaired pulmonary function.
• Major surgery within 4 weeks or minor surgery within 1 week (e.g., tooth extraction).
• Vaccination within 30 days before the first dose.
• Abdominal fistula, GI perforation, or abscess within 4 weeks.
• Any clinically significant abnormality affecting safety per investigator, including: Active infection requiring systemic therapy; Uncontrolled diabetes/hypertension (BP \>140/90 mmHg despite ≤2 antihypertensives); Myocardial infarction within 6 months; Thyroid dysfunction (\>NCI CTCAE v4.0 Grade 1).

Sponsors & Collaborators

• West China Hospital: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (18)

• Moore C, Hsu CC, Chen WM, Chen BPC, Han C, Story M, Aguilera T, Pop LM, Hannan R, Fu YX, Saha D, Timmerman R. Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) in Preclinical Models Enhances Single-Agent Immune Checkpoint Blockade. Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1306-1316. doi: 10.1016/j.ijrobp.2021.03.047. Epub 2021 Mar 29.

  PMID: 33794306 RESULT

• Peng H, Moore C, Zhang Y, Saha D, Jiang S, Timmerman R. An AI-based approach for modeling the synergy between radiotherapy and immunotherapy. Sci Rep. 2024 Apr 8;14(1):8250. doi: 10.1038/s41598-024-58684-6.

  PMID: 38589494 RESULT

• Rouf S, Moore C, Saha D, Nguyen D, Bleile M, Timmerman R, Peng H, Jiang S. PULSAR Effect: Revealing potential synergies in combined radiation therapy and immunotherapy via differential equations. J Theor Biol. 2025 Jan 7;596:111974. doi: 10.1016/j.jtbi.2024.111974. Epub 2024 Oct 22.

  PMID: 39448025 RESULT

• Peng H, Moore C, Saha D, Jiang S, Timmerman R. Understanding the PULSAR effect in combined radiotherapy and immunotherapy using transformer-based attention mechanisms. Front Oncol. 2024 Dec 2;14:1497351. doi: 10.3389/fonc.2024.1497351. eCollection 2024.

  PMID: 39687891 RESULT

• Wainberg ZA, Melisi D, Macarulla T, Pazo Cid R, Chandana SR, De La Fouchardiere C, Dean A, Kiss I, Lee WJ, Goetze TO, Van Cutsem E, Paulson AS, Bekaii-Saab T, Pant S, Hubner RA, Xiao Z, Chen H, Benzaghou F, O'Reilly EM. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281. doi: 10.1016/S0140-6736(23)01366-1. Epub 2023 Sep 11.

  PMID: 37708904 RESULT

• Cho YB, Yoon N, Suh JH, Scott JG. Radio-immune response modelling for spatially fractionated radiotherapy. Phys Med Biol. 2023 Aug 7;68(16):165010. doi: 10.1088/1361-6560/ace819.

  PMID: 37459862 RESULT

• Moon EJ, Petersson K, Olcina MM. The importance of hypoxia in radiotherapy for the immune response, metastatic potential and FLASH-RT. Int J Radiat Biol. 2022;98(3):439-451. doi: 10.1080/09553002.2021.1988178. Epub 2021 Nov 2.

  PMID: 34726575 RESULT

• Galluzzi L, Aryankalayil MJ, Coleman CN, Formenti SC. Emerging evidence for adapting radiotherapy to immunotherapy. Nat Rev Clin Oncol. 2023 Aug;20(8):543-557. doi: 10.1038/s41571-023-00782-x. Epub 2023 Jun 6.

  PMID: 37280366 RESULT

• Zhu X, Liu W, Cao Y, Feng Z, Zhao X, Jiang L, Ye Y, Zhang H. Immune profiling of pancreatic cancer for radiotherapy with immunotherapy and targeted therapy: Biomarker analysis of a randomized phase 2 trial. Radiother Oncol. 2024 Jan;190:109941. doi: 10.1016/j.radonc.2023.109941. Epub 2023 Oct 10.

  PMID: 37820884 RESULT

• Li X, Hou W, Xiao C, Yang H, Zhao C, Cao D. Panoramic tumor microenvironment in pancreatic ductal adenocarcinoma. Cell Oncol (Dordr). 2024 Oct;47(5):1561-1578. doi: 10.1007/s13402-024-00970-6. Epub 2024 Jul 15.

  PMID: 39008192 RESULT

• Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, Rosenberg SA. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010 Oct;33(8):828-33. doi: 10.1097/CJI.0b013e3181eec14c.

  PMID: 20842054 RESULT

• Lynch C, Pitroda SP, Weichselbaum RR. Radiotherapy, immunity, and immune checkpoint inhibitors. Lancet Oncol. 2024 Aug;25(8):e352-e362. doi: 10.1016/S1470-2045(24)00075-5.

  PMID: 39089313 RESULT

• Wandmacher AM, Letsch A, Sebens S. Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer. Cancers (Basel). 2021 Aug 23;13(16):4235. doi: 10.3390/cancers13164235.

  PMID: 34439389 RESULT

• Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.

  PMID: 22658128 RESULT

• Brautigam K, Skok K, Szymonski K, Rift CV, Karamitopoulou E. Tumor immune microenvironment in pancreatic ductal adenocarcinoma revisited - Exploring the "Space". Cancer Lett. 2025 Jul 10;622:217699. doi: 10.1016/j.canlet.2025.217699. Epub 2025 Apr 7.

  PMID: 40204149 RESULT

• Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.

  PMID: 24131140 RESULT

• Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.

  PMID: 21561347 RESULT

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Drug Therapy; Immunotherapy; DEAE-Dextran

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy; Dextrans; Glucans; Polysaccharides; Carbohydrates

Central Study Contacts

Kexun Zhou, Dr.

CONTACT

+028 85423609; kexunzhou@wchscu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 9, 2026
• First Posted: May 19, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: May 19, 2026

Record last verified: 2026-05

Locations

CN (1)