Safety and Efficacy of Multimodal Thermal Therapy (MTT) Combined With KRAS G12V mRNA Vaccine, S-1, and Sintilimab in Patients With Metastatic Pancreatic Cancer

A Study of Multimodal Thermal Therapy (MTT) Combined With KRAS G12V mRNA Vaccine, S-1, and Sintilimab for Safety and Efficacy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma Who Have Disease Progression After or Are Intolerant to Standard First-Line Therapy

This is a single-arm, single-center, exploratory clinical study. A total of 20 participants with metastatic pancreatic ductal adenocarcinoma (with liver or lung metastasis) who have experienced disease progression after or are intolerant to standard first-line chemotherapy (based on the AG regimen [Albumin-bound Paclitaxel plus Gemcitabine]) will be enrolled.The study aims to evaluate the safety, efficacy, and underlying immunological mechanisms of Multimodal Thermal Therapy (MTT) combined with a KRAS G12V mRNA vaccine, S-1, and Sintilimab.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Neoplasms; Liver Neoplasms; Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Device: Multimodal Thermal Therapy (MTT) System; Biological: KRAS G12V mRNA Vaccine; Drug: Sintilimab; Drug: S-1

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: baiyong shen; Phone Number: +86 18817821319; Email: shenby@shsmu.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: baiyong shen; Phone Number: +86 18817821319; Email: shenby@shsmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged ≥ 18 years old with no restriction on gender.
• Patients with advanced pancreatic cancer or postoperative recurrent pancreatic cancer confirmed by histopathological or cytological examination.
• Tumor tissues are confirmed to carry KRAS G12V mutation via sequencing and bioinformatics analysis (valid test reports obtained within the previous 12 months and recognized by the investigator are acceptable). In the dose expansion phase, patients must harbor at least one HLA allele capable of effectively presenting the corresponding antigen, including HLA-A11:01, HLA-A03:01, HLA-A30:01, HLA-A68:01, HLA-C01:02, HLA-C03:03, and HLA-C03:04.
• Disease resistance or intolerance to prior AG-based chemotherapy regimens.
• Presence of liver metastasis or lung metastasis.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Child-Pugh score ≤ 7 points.
• Expected overall survival of at least 3 months.

Exclusion Criteria:

• Presence of diffuse hepatic or pulmonary metastases.
• Prior local treatment including radiofrequency ablation, microwave ablation, radiotherapy or other local therapies for metastatic lesions.
• Current participation in other interventional clinical studies and receiving investigational treatment.
• Diagnosis of any other malignant disease within 5 years prior to the first study drug administration (excluding radically treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or radically resected in situ carcinoma).
• Prior history of solid organ or hematopoietic stem cell transplantation.
• Any disease requiring systemic treatment with corticosteroids (prednisone or equivalent daily dose > 10 mg) or other immunosuppressive agents within 14 days prior to enrollment.
• Previous or current diagnosis of brain metastases with incompletely controlled symptoms (i.e., persistent or aggravated symptoms, or requirement for adjusted symptomatic treatment to maintain symptom relief).
• Presence of uncontrolled active infection.
• Renal dysfunction defined as serum creatinine > 176.8 μmol/L or creatinine clearance < 30 mL/min.
• Uncorrectable coagulation abnormalities, including platelet count < 50×10⁹/L, prothrombin time > 18 seconds, or prothrombin activity < 40%, which cannot be corrected.
• History of esophagogastric variceal rupture without effective treatment via endoscopy, interventional therapy or surgery.
• Patients with psychiatric disorders in the acute episode stage.
• Women of childbearing potential who are pregnant, breastfeeding, or planning to become pregnant during the study treatment period or within 3 months after the end of study treatment.
• Prior systemic pharmacotherapy, radiotherapy or local hepatic treatment with an interval of < 1 month from the last systemic or local hepatic treatment to the first study drug administration.

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: Treatment Group; MTT + KRAS G12V mRNA Vaccine + Sintilimab ± S-1 Participants will receive Multimodal Thermal Therapy (MTT) combined with KRAS G12V mRNA vaccine and sintilimab. In addition, oral S-1 (tegafur/gimeracil/oteracil) will be administered to participants aged <80 years. Participants aged ≥80 years will receive MTT + KRAS G12V mRNA vaccine + sintilimab without S-1.

Device: Multimodal Thermal Therapy (MTT) System; The MTT system is a medical device that performs sequential ablation therapy. Treatment consists of initial cryoablation followed immediately by radiofrequency ablation (RFA) to achieve a synergistic thermal effect against the tumor.; Biological: KRAS G12V mRNA Vaccine; Administered via intramuscular injection at a dose of 1 mg. The first dose will be given 1 to 3 days after Multimodal Thermal Therapy (MTT). Subsequent doses will be administered every 3 weeks (Q3W) according to the study dosing schedule and clinical discretion.; Drug: Sintilimab; Administered via intravenous infusion at a dose of 200 mg on Day 1 (d1). Treatment will begin on 7 days after MTT and will be repeated every 3 weeks (Q3W) until disease progression or unacceptable toxicity.; Drug: S-1; Only participants aged <80 years will receive oral S-1. Treatment starts on Day 7 after MTT at a dose of 40-60 mg twice daily (bid) on Days 1 to 14 (d1-14) of each cycle. Cycles are repeated every 3 weeks (Q3W) until disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events (CTCAE v6.0)	To assess the safety profile of the combination regimen (MTT + KRAS G12V mRNA vaccine + Sintilimab ± S-1) in patients with metastatic pancreatic cancer. Safety will be evaluated by recording the incidence, type, and maximum grade of adverse events (AEs) and serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.	From the start of treatment up to 90 days after the last dose (or end of treatment).
Frequency of Dose Modifications and Treatment Discontinuations	To evaluate patient tolerability to the multimodal regimen. Tolerability is defined as the ability of participants to receive the full planned treatment. Specifically, it measures the proportion of participants requiring dose modifications, treatment delays, treatment interruptions, or permanent discontinuation of any component of the therapy (MTT, S-1 [for those <80 years], Sintilimab, or mRNA vaccine) due to adverse events.	From the start of treatment up to 90 days after the last dose (or end of treatment).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (RECIST 1.1)	Time from the date of first study intervention to the date of radiographic disease progression per RECIST version 1.1, death from any cause, or the date of the last effective follow-up. Radiographic assessments will be performed every 1-2 months using contrast-enhanced abdominal MRI or CT imaging.	From the date of first study intervention until disease progression, death, or the last effective follow-up (up to approximately 24 months)
Overall Survival	Time from the date of first study intervention to the date of death from any cause or the date of the last confirmed survival follow-up. Long-term survival will be tracked through regular follow-up visits until death, loss to follow-up, or study termination.	up to approximately 36 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 13, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: July 1, 2026
• First Submitted That Met QC Criteria: July 30, 2026
• First Posted (Actual): August 4, 2026

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: mRNA; Metastatic Pancreatic Cancer; Multimodal Thermal Therapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Liver Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Liver Neoplasms; Therapeutics; Drug Therapy; Drug Delivery Systems; sintilimab; S 1 (combination)
• Other Study ID Numbers: PLP1-13114

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