KRAS neoantigen nanovaccine to help prevent recurrence after colorectal or pancreatic cancer surgery

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

This trial tests a KRAS-targeting nanovaccine made from engineered Lactococcus lactis membranes as adjuvant therapy for adults with resected colorectal or pancreatic cancer who have specific KRAS mutations.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, cyclophosphamide
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07353645 on ClinicalTrials.gov

What this trial studies

The vaccine platform uses bacterial-membrane nanovesicles from an engineered Lactococcus lactis that present KRAS antigenic peptides to stimulate an anti-tumor immune response. Phase 1 uses a 3+3 dose-escalation design at two dose levels (1.5 mg and 3.0 mg) with nine planned vaccinations delivered subcutaneously or by ultrasound-guided inguinal lymph node injection. The expansion phase tests the vaccine combined with anti-PD-1 and anti-CTLA-4 antibodies. Key outcomes are safety, vaccine-induced immune responses, and preliminary relapse-free survival with radiographic monitoring every 12 weeks for two years then every 24 weeks thereafter.

Who should consider this trial

Good fit: Adults aged 18–75 with ECOG 0–1 who had R0 resection for colorectal (stage III) or pancreatic (stage I–III) adenocarcinoma, completed at least four cycles of adjuvant chemotherapy, have no radiologic recurrence, and harbor specified KRAS hotspot mutations are eligible.

Not a fit: Patients without the listed KRAS hotspot mutations, with active metastatic disease, poor performance status, or failing the specified blood and biochemical criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the vaccine could lower the risk of cancer recurrence by inducing KRAS-specific immune responses in patients after surgery.

How similar studies have performed: Early clinical and preclinical neoantigen vaccine efforts have shown immunogenicity signals, but KRAS-targeted nanovaccines are a novel approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* Age ≥18 years and ≤75 years, with an ECOG performance status of 0-1.
* Patients with histologically confirmed colorectal adenocarcinoma or pancreatic adenocarcinoma who have undergone radical resection (R0) and completed at least 4 cycles of postoperative adjuvant chemotherapy.
* Postoperative pathological stage for colorectal cancer is IIIA, IIIB, or IIIC. For pancreatic cancer, postoperative pathological stage is I, II, or III. The tumor must harbor at least one of the following KRAS hotspot mutations: G12D, G12V, G12R, G12A, G12S, G12C, or G13D.
* No radiological evidence of tumor recurrence or metastasis.
* Patients must meet the following hematologic criteria: Lymphocyte count ≥0.5×10⁹/L, neutrophil count ≥1.5×10⁹/L, white blood cell count \>2.5×10⁹/L; Hemoglobin ≥90 g/L; Platelet count ≥90×10⁹/L.
* Patients must meet the following biochemical criteria: Total bilirubin ≤1.5 × upper limit of normal (ULN); AST and ALT ≤1.5 × ULN; Serum creatinine ≤1.5 × ULN or creatinine clearance ≥30 mL/min.
* Patients must meet the following coagulation criteria: INR or PTT ≤1.5 × ULN.
* Patients of childbearing potential must employ adequate contraception or other birth control methods before enrollment and throughout the trial.
* Signed informed consent form has been obtained.
* Ability to comply with the study protocol and follow-up procedures.

Exclusion Criteria:

* Patients with colorectal cancer exhibiting microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) or harboring BRAF mutations.
* Pancreatic cancer patients with neuroendocrine tumor components are excluded.
* Patients with a history of other malignancies, except for carcinoma in situ of the cervix, treated squamous cell carcinoma or bladder epithelial tumors (Ta and TIS), or other malignancies that have been curatively treated (at least 5 years prior to enrollment).
* Prior treatment with anticancer vaccines or any antibodies targeting T-cell co-regulatory proteins (e.g., anti-PD1, anti-PDL1, or anti-CTLA4).
* Patients with HIV, HCV, or HBV infection; uncontrolled coronary artery disease or asthma; uncontrolled cerebrovascular disease; or any other condition deemed by the investigator as grounds for exclusion.
* Patients who are on immunosuppressants or systemic corticosteroid therapy for immunosuppressive purposes (at a dose \>10 mg/day prednisone or equivalent) and have continued use within 2 weeks prior to enrollment.
* Poorly controlled cardiac clinical symptoms or diseases, such as: Heart failure of NYHA Class II or higher; Unstable angina; Myocardial infarction within the past year; Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; QTc \>450 ms (males); QTc \>470 ms (females).
* Abnormal coagulation function (INR \>2.0, PT \>16 s), bleeding tendency, or current thrombolytic or anticoagulant therapy. Prophylactic use of low-dose aspirin or low molecular weight heparin is allowed.
* Patients with active infection; unexplained fever ≥38.5°C within 7 days prior to medication; baseline white blood cell count \>15×10⁹/L; or suppurative and chronic infections with non-healing wounds.
* Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
* Substance abuse, or clinical, psychological, or social factors that may affect the provision of informed consent or the conduct of the study.
* Known or suspected allergy to drugs used in immunotherapy.
* Inability to undergo immunological and clinical follow-up assessments.
* Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
* Participation in other interventional drug clinical trials concurrently.

Where this trial is running

Nanjing, Jiangsu

• Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Baorui Liu

Conditions Colorectal Cancer; Pancreatic Cancer