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

Phase 2Not Yet RecruitingNCT07745790

Ruijin Hospital20 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pancreatic Ductal Adenocarcinoma Liver Neoplasms Lung Neoplasms

Interventions

KRAS G12V mRNA VaccineBIOLOGICAL

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.

S-1DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: From the start of treatment up to 90 days after the last dose (or end of treatment).

Secondary Outcomes

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.

Time frame: 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.

Time frame: up to approximately 36 months