LDRT Combined With Pucotenlimab and Standard Therapy for Advanced Pancreatic Cancer: A Single-Arm Study

NCT ID: NCT07312422

Last Updated: 2025-12-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2026-10-30

Brief Summary

To investigate the activating effect of local lesion low-dose radiotherapy (2Gy) on the tumor immune microenvironment, and the efficacy, safety, and feasibility of its combination with pembrolizumab and standard therapy in patients with advanced pancreatic cancer. Concurrently, to preliminarily establish an efficacy prediction model for the early identification of patient populations who would benefit from the treatment, thereby providing a theoretical foundation for the implementation of precision medicine.

Detailed Description

Pancreatic cancer is one of the most malignant digestive tract tumors, with an extremely poor prognosis and a five-year survival rate of less than 10%. Its treatment options are limited. For patients with unresectable, advanced disease, systemic chemotherapy (such as the AG regimen or FOLFIRINOX regimen) is the standard treatment, but the efficacy remains unsatisfactory, with median overall survival struggling to exceed one year.

In recent years, immunotherapy represented by PD-1/PD-L1 inhibitors has achieved revolutionary success in various solid tumors (such as lung cancer, melanoma), bringing hope for long-term survival to patients with advanced cancer. However, in the field of pancreatic cancer, immunotherapy monotherapy has repeatedly faced setbacks. Multiple clinical studies show that immune checkpoint inhibitors have a very low response rate (typically <5%) in unselected patients with advanced pancreatic cancer, with the vast majority failing to benefit. This characteristic of being an immunologically "cold" tumor is largely attributed to the unique tumor microenvironment (TME) of pancreatic cancer: a highly fibrotic stroma, minimal infiltration of cytotoxic T lymphocytes (CTLs), and an abundance of immunosuppressive cells (such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs)). These factors collectively create a state of immune exclusion and immunosuppression, preventing immune cells from recognizing and attacking tumor cells.

To convert "cold tumors" into "hot tumors," researchers are actively exploring various combination strategies. Among them, the combination of radiotherapy (RT) and immunotherapy shows great potential. Traditionally, radiotherapy was considered merely a local treatment modality. However, recent studies have found that it also has the abscopal effect - where irradiation of one lesion can lead to the shrinkage of non-irradiated, distant lesions. This suggests that radiotherapy can activate a systemic anti-tumor immune response. It is noteworthy that low-dose radiotherapy (e.g., 2Gy) plays a unique role in this process. Unlike high-dose radiotherapy, which primarily causes DNA double-strand breaks in tumor cells, low-dose radiotherapy is more capable of inducing immunogenic cell death (ICD), prompting tumor cells to release antigens and danger signal molecules, thereby enhancing antigen presentation by dendritic cells (DCs) and initiating a T-cell immune response. Multiple preclinical studies have confirmed that 2Gy radiotherapy can effectively promote the cross-presentation of tumor-specific antigens, reduce immunosuppression in the microenvironment, and increase the infiltration of lymphocytes into the tumor site, creating favorable conditions for immunotherapy to take effect.

Based on the above evidence, we propose the following scientific hypothesis: For patients with advanced pancreatic cancer who are insensitive to immunotherapy monotherapy, preemptive intervention using low-dose radiotherapy is expected to remodel the tumor immune microenvironment (TIME), converting it from "cold" to "hot." Subsequently, the follow-up combination of a PD-1 inhibitor (Pucotenlimab) and standard chemotherapy could not only activate the immune system via radiotherapy but also further kill tumor cells and expose more tumor antigens through chemotherapy, potentially suppressing immunosuppressive cells. The synergistic effect of these three modalities is expected to achieve a "1+1+1>3" outcome, potentially breaking through the current therapeutic bottleneck for advanced pancreatic cancer.

Conditions

Pancreatic Cancer; PD-L1; PD-1 Inhibitor; LDRT; Proterizumab

Keywords

pancreatic cancer; PD-1 inhibitor; LDRT; immunotherapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A Study of Low-Dose Radiotherapy Combined with Pucotenlimab and AG Chemotherapy

Day 1: Administer low-dose radiation therapy (2 Gy per fraction, 1 fraction per cycle) to radiotherapy-eligible lesions.

Day 2: Initiate intravenous infusion of Pucotenlimab (200 mg) to be completed before 10:30 AM.

Day 2: Sequentially administer standard chemotherapy regimens (e.g., AG or FOLFIRINOX) following the Pucotenlimab infusion.

Cycle Duration: Each treatment cycle is repeated every 21 days.

Group Type: EXPERIMENTAL

low dose radiotherapy combined with immune combined chemotherapy

Intervention Type: DRUG

Specific Protocol:

Induction Phase (Week 1): Low-dose radiotherapy once (2 Gy/1 fx).

Consolidation Phase (Starting from Week 2): Pembrolizumab combined with AG regimen.

Maintenance Phase (After 6 months): Pembrolizumab monotherapy.

Interventions

low dose radiotherapy combined with immune combined chemotherapy

Specific Protocol:

Induction Phase (Week 1): Low-dose radiotherapy once (2 Gy/1 fx).

Consolidation Phase (Starting from Week 2): Pembrolizumab combined with AG regimen.

Maintenance Phase (After 6 months): Pembrolizumab monotherapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years, regardless of gender;
• ECOG score of 0 to 1;
• Patients with histologically or cytologically confirmed pancreatic malignancy;
• No prior treatment with PD-1 or PD-L1 inhibitors;
• Presence of a radiotherapeutically eligible target lesion (excluding bone metastases);
• Subjects voluntarily participate in the study and provide signed informed consent.

Exclusion Criteria

• Previous history of radiotherapy;
• Uncontrolled chronic infectious or non-infectious diseases, including but not limited to: medication-refractory heart failure, poorly controlled hypertension, etc.;
• Active or clinically uncontrolled severe infections;
• History of psychoactive drug abuse that cannot be abstained from, or patients with psychiatric disorders;
• Pregnant or lactating women, or patients of childbearing potential who are unwilling or unable to adopt effective contraceptive measures;
• Other conditions deemed by the investigator as potentially affecting the conduct of the clinical study or the interpretation of study results.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Liu Yang

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Liu Yang, M.D.

Role: CONTACT

Phone: 13666601475

Email: yangliuqq2003@163.com

Facility Contacts

Liu Yang, M.D.

Role: primary

Other Identifiers

Pucotenlimab in PDAC

Identifier Type: -

Identifier Source: org_study_id