Inhaled mRNA Immunotherapy for Patients With Advanced Lung Cancer or Pulmonary Metastatic Solid Tumors

This is an open-label, single-arm, phase I master platform clinical trial designed to assess the safety, tolerability, pharmacokinetic profiles and preliminary anti-tumor activity of multiple investigational inhaled in-vivo mRNA multi-target immunotherapy candidates in adult subjects diagnosed with unresectable locally advanced or metastatic solid tumors.

The study adopts the standard 3+3 dose-escalation design for each individual mRNA product. Eligible participants will receive study drug via pulmonary inhalation on predefined treatment cycles with gradual dose increment across sequential cohorts to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). After completion of dose escalation, an optional expansion cohort at RP2D will be enrolled to further characterize safety and preliminary anti-tumor efficacy.

All enrolled patients will undergo regular safety monitoring including adverse event recording, laboratory examinations, pulmonary function test and radiological tumor assessment per protocol schedule. The primary study endpoints focus on treatment-related adverse events and MTD determination; secondary endpoints include objective response rate, disease control rate, duration of response as well as pharmacokinetic parameters of inhaled mRNA agents. Subjects will continue assigned study treatment until confirmed disease progression, unacceptable toxicity, withdrawal of consent or study closure.

Inclusion criteria

• Male or female patients aged ≥ 18 years.
• Confirmed diagnosis of advanced lung cancer (driver gene negative or targeted therapy failed) or pulmonary metastatic solid tumors, with no standard treatment options available or who have failed prior standard therapies.
• Presence of at least one measurable lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function, including hematologic, hepatic, and renal function.
• Ability to understand and sign the informed consent form.
• Expected survival of at least 12 weeks.

Exclusion criteria

• History of severe hypersensitivity to mRNA-based therapies or components of the study drug.
• Uncontrolled active infection or severe underlying respiratory disease (e.g., severe COPD, asthma requiring high-dose steroids).
• Prior allogeneic stem cell or solid organ transplantation.
• Current use of other investigational agents within 4 weeks before the first dose of study treatment.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Pregnant or breastfeeding women.
• Any condition that, in the investigator's opinion, would interfere with study compliance or safety.