RGL-270 + ICI in Advanced NSCLC

Inclusion criteria

• apply.

Exclusion criteria

• Histologically/cytologically confirmed small cell lung cancer (SCLC), mixed tumors with SCLC components, neuroendocrine tumors with large cell components, or sarcomatoid carcinoma.
• Actionable driver mutations (e.g., EGFR/ALK) where targeted therapy is accessible per investigator assessment, except for patients refusing targeted treatment.
• Prior radiotherapy within 5 years or history of immunotherapy/cancer vaccines (including but not limited to TILs, CAR-T, TCR-T, therapeutic cancer vaccines).
• Live vaccines administered ≤28 days pre-screening or planned during study/within 90 days post-treatment (inactivated vaccines permitted).
• Investigator-assessed contraindications for immunotherapy.
• Active autoimmune diseases (exclusion: hypothyroidism from autoimmune thyroiditis requiring hormone replacement only).
• Evidence of active tuberculosis within 1 year pre-screening, regardless of treatment.
• History of interstitial lung disease (ILD), suspected active ILD on screening CT, or idiopathic pulmonary fibrosis/organizing pneumonia (e.g., BOOP/cryptogenic OP).
• Severe active infection requiring IV antibiotics/antifungals/antivirals ≤28 days pre-screening or during screening.
• Clinically uncontrolled effusions requiring drainage ≤14 days pre-screening (pleural/peritoneal/pericardial).
• Hypersensitivity to study drug excipients or severe vaccine allergy history.
• Other malignancies within 5 years (exceptions: cured cervical CIS, basal/squamous skin cancer, localized prostate cancer post-radical therapy, DCIS, papillary thyroid cancer).
• Allogeneic organ or hematopoietic stem cell transplantation.
• Congenital/acquired immunodeficiency (e.g., DiGeorge syndrome, T-/B-cell deficiencies, Wiskott-Aldrich, ataxia-telangiectasia, CVID) or HIV infection.
• Active hepatitis B (defined as positive hepatitis B surface antigen \[HBsAg\] at screening AND HBV DNA ≥500 IU/mL or above the upper limit of normal \[ULN\] at the local institution), OR active hepatitis C (defined as positive hepatitis C antibody \[HCV-Ab\] at screening AND detectable HCV-RNA).
• Uncontrolled or significant cardiovascular disease, including:
• Symptomatic congestive heart failure (NYHA Class III or IV) Myocardial infarction within 6 months prior to screening Unstable angina within 1 month prior to screening Clinically significant arrhythmias requiring therapeutic intervention Refractory hypertension despite adequate treatment (systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg)
• Any other condition deemed by the investigator to potentially compromise trial conduct or outcome interpretation, including but not limited to:
• Anticipated poor compliance with study procedures Comorbidities posing unacceptable safety risks Insufficient neoantigen burden for vaccine production (based on tumor sequencing analysis) Vaccine manufacturing failure
• Subjects who experienced severe irAE during the run-in treatment period resulting in permanent discontinuation of PD-1/PD-L1 inhibitors.
• If a subject experiences comprehensive disease progression during the introduction treatment but only has clinical deterioration, or if the intracranial lesion stabilizes after local treatment and the investigator assesses that medication can continue, they are allowed to continue participating in the study.