NCT07353645

KRAS Neoantigen Nanovaccine as Adjuvant Therapy for Colorectal Cancer/Pancreatic Cancer

Phase I/II Clinical Study of KRAS Neoantigen Nanovaccine as Adjuvant Therapy for Colorectal Cancer/Pancreatic Cancer With High Risk of Recurrence

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial will utilize a neoantigen nanovaccine constructed from the bacterial membranes of an engineered Lactococcus lactis strain (FOLactis). This platform, independently developed by our center, expresses KRAS antigenic peptides. The vaccine will be administered as adjuvant therapy to post-operative patients with colorectal or pancreatic cancer who carry KRAS mutations and are at high risk of recurrence. The study aims to assess the safety, immunogenicity, and preliminary efficacy of this neoantigen nanovaccine in a clinical setting.

Detailed description

1. Pre-vaccination Screening: Detection of KRAS hotspot mutations in the patient's tumor tissue. 2. Vaccine Composition and Administration: The vaccine utilizes a neoantigen nanovaccine constructed from the bacterial membranes of engineered Lactococcus lactis, independently developed by the Cancer Center of Nanjing Drum Tower Hospital. It is administered via subcutaneous or intralymph node injection. The study consists of two phases: Dose Escalation and Dose Expansion. The Dose Escalation phase involves the vaccine alone, while the Dose Expansion phase combines the vaccine with anti-PD-1 antibody and anti-CTLA-4 antibody, as detailed below: Dose Escalation Phase: Conducted according to a "3+3" design. The neoantigen nanovaccine is tested at two dose levels: 1.5mg and 3.0mg. Each injection has a total volume of 2.0ml, administered subcutaneously or via ultrasound-guided injection into bilateral inguinal lymph nodes. Vaccination Schedule: A total of 9 vaccinations are planned on Days 1, 4, 8, 15, 22, 43, 64, 85, and 106. Vaccinations #1 and #5-#9: Ultrasound-guided bilateral inguinal lymph node injection combined with subcutaneous injection in the subdeltoid region,accompanied by intravenous cyclophosphamide (200mg/m²) on the same day. Vaccinations #2, #3, and #4: Subcutaneous injection. Efficacy and Safety Monitoring: Radiographic efficacy evaluations are performed every 12 weeks for the first two years post-surgery, and every 24 weeks thereafter. Adverse events are assessed following each vaccination. Dose Expansion Phase: The vaccine dose for this phase is determined based on results from the Dose Escalation phase. The vaccination procedure remains the same. Twenty eligible post-operative colorectal cancer patients and twenty eligible post-operative pancreatic cancer patients will be enrolled for continued observation of efficacy and side effects. The nanovaccination schedule follows the Dose Escalation phase protocol. The anti-CTLA-4 antibody is administered on D1 and D43. The anti-PD-1 antibody is administered starting on the first day of vaccination, once every three weeks, until disease progression, unacceptable toxicity, or completion of 6 cycles, whichever occurs first. 3. Immunological Follow-up: Hematological immune monitoring, including lymphocyte immunophenotyping and cytokine profiling, is performed pre-vaccination and on Days 1, 22, 43, 85, and 106 after the first vaccination.

Conditions

• Colorectal Cancer
• Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	KRAS Neoantigen Nanovaccine	The vaccine utilizes a neoantigen nanovaccine constructed from the bacterial membranes of engineered Lactococcus lactis, independently developed by the Cancer Center of Nanjing Drum Tower Hospital. It is administered via subcutaneous or intralymph node injection.

Timeline

• Start date: 2026-03-23
• Primary completion: 2029-01-01
• Completion: 2031-01-01
• First posted: 2026-01-20
• Last updated: 2026-04-15

Locations

1 site across 1 country: China