Safety and Efficacy of Neoantigen-Based Personalized Immunotherapy as Consolidation Therapy After Standard Adjuvant Treatment in Resectable Stage III Colorectal Cancer or Non-Small Cell Lung Cancer

A Clinical Study on the Safety and Efficacy of Personalized Immunotherapy Based on Neoantigens as Consolidation Therapy Following Standard Postoperative Adjuvant Treatment in Patients With Stage III Resectable Colorectal Cancer or Non-Small Cell Lung Cancer

The primary objective of this study is to evaluate the safety, efficacy, and methodological feasibility of sequential administration of neoantigen-based personalized immunotherapy following completion of standard adjuvant therapy in patients with colorectal cancer or non-small cell lung cancer who have undergone radical resection.

Based on previous safety clinical trial results of personalized anti-tumor neoantigen injections, the 300 μg/peptide dose is well tolerated.

Therefore, this study will assess the safety and preliminary efficacy of personalized anti-tumor neoantigen injections at a dose of 300 μg/peptide as consolidation therapy after standard postoperative adjuvant treatment in patients with stage III resectable colorectal cancer or non-small cell lung cancer, aiming to provide novel personalized therapeutic strategies to improve disease-free survival (DFS) and overall survival (OS) in these patients.

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 80 years;

2. Voluntarily signed written informed consent;

3. Agreed to provide tumor tissue and whole blood for sequencing; or able to supply raw gene sequencing data required for tumor neoantigen analysis and design of personalized anti-tumor neoantigen injection, including whole-exome sequencing data of tumor tissue, transcriptome sequencing data, and whole-exome sequencing data of peripheral blood;

4. Patients with pathologically confirmed, clinically diagnosed Stage III resectable colorectal cancer or non-small cell lung cancer;

5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;

6. Underwent radical resection of lesions;

7. Received postoperative adjuvant therapy in accordance with standard guideline-recommended regimens, completed the full guideline-recommended treatment cycles, and no new lesions were detected on imaging examinations;

8. Complete imaging records must be available within 1 week prior to initiation of personalized immunotherapy, including but not limited to whole-body PET-CT and brain MRI. If whole-body PET-CT is not feasible, chest CT, contrast-enhanced abdominal CT, or bone ECT is required;

9. Adequate organ and bone marrow function:

   • White blood cell count ≥ 3,500/mcL
   • Absolute lymphocyte count > 800/mcL
   • Absolute neutrophil count > 1,500/mcL
   • Platelet count > 100,000/mcL
   • Hemoglobin > 10.0 g/dL
   • Total serum bilirubin < 1.5 × upper limit of normal (ULN)
   • AST/ALT < 2.0 × ULN
   • Serum creatinine < 1.5 × ULN

10. For pregnant or lactating women: female subjects of childbearing potential must have a negative pregnancy test within 7 days before enrollment, have no childbearing plan in the near term, and be willing to use effective contraceptive measures (contraception or other birth control methods) before and during the study;

11. Male patients willing to use appropriate contraceptive measures;

12. Able to comply with the study protocol and follow-up procedures.

Exclusion Criteria:

1. Poor general condition unsuitable for surgery or postoperative adjuvant therapy;
2. New lesions detected on imaging after completion of postoperative adjuvant therapy;
3. Received immunotherapy or other investigational medicinal products prior to surgery;
4. Presence of other malignancies, except for cured basal cell carcinoma, thyroid carcinoma, cervical dysplasia, etc., and those who have been disease-free for more than 5 years and are considered at low risk of recurrence by the investigator;
5. No actionable neoantigens identified for personalized immunotherapy after analysis of sequencing data;
6. Prior history of bone marrow transplantation or stem cell transplantation;
7. Concomitant use of any other anti-tumor drugs, anti-tumor therapies in other clinical trials, immunosuppressive agents, or long-term systemic glucocorticoids;
8. Received any other vaccination within 4 weeks before treatment; Infection with HIV, HCV, or HBV; severe asthma; autoimmune disease or immunodeficiency; or immunosuppressed status (excluding vitiligo, type 1 diabetes, autoimmune hypothyroidism requiring hormonal therapy, and psoriasis not requiring systemic treatment);
9. Uncontrolled comorbidities including but not limited to active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia;
10. Herpes virus infection (except those with scab formation for more than 4 weeks);
11. Respiratory viral infection (except those recovered for more than 4 weeks);
12. Severe coronary artery disease or cerebrovascular disease, or other diseases deemed ineligible by the investigator;
13. Drug abuse, or clinical, psychological, or social factors that would compromise informed consent or compliance with the study;
14. History of severe allergy to food, drugs, or vaccines, or potential allergy to immunotherapy as judged by the investigator.