Neoplasm Metastasis, Neoplasms, Solid Tumors
Conditions
Brief summary
This is an open-label phase I master platform study to evaluate the safety, tolerability and preliminary anti-tumor efficacy of multiple inhaled in-vivo mRNA immunotherapies in adult patients with advanced solid tumors. Subjects will receive inhalation mRNA formulations at ascending dose levels following a 3+3 dose-escalation design to determine maximum tolerated dose and recommended phase II dose.
Detailed description
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.
Interventions
BIOLOGICALInhaled mRNA
Inhaled mRNA dry powder formulation, administered via a low-resistance dry powder inhaler.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label study, no blinding implemented.
Intervention model description
Single-arm open-label phase I trial with standard 3+3 dose-escalation design for multiple inhaled mRNA immunotherapy agents.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged ≥ 18 years. 2. 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. 3. Presence of at least one measurable lesion according to RECIST v1.1. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Adequate organ function, including hematologic, hepatic, and renal function. 6. Ability to understand and sign the informed consent form. 7. Expected survival of at least 12 weeks.
Exclusion criteria
1. History of severe hypersensitivity to mRNA-based therapies or components of the study drug. 2. Uncontrolled active infection or severe underlying respiratory disease (e.g., severe COPD, asthma requiring high-dose steroids). 3. Prior allogeneic stem cell or solid organ transplantation. 4. Current use of other investigational agents within 4 weeks before the first dose of study treatment. 5. Active autoimmune disease requiring systemic immunosuppressive therapy. 6. Pregnant or breastfeeding women. 7. Any condition that, in the investigator's opinion, would interfere with study compliance or safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | From the first dose of study treatment up to 30 days after the last dose. | The primary endpoint is to assess the safety and tolerability of inhaled mRNA immunotherapy, including the incidence and severity of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) / Recommended Phase 2 Dose (RP2D) | Up to 28 days after the last dose in each dose cohort. | To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of inhaled mRNA immunotherapy using a standard 3+3 dose-escalation design. |
Outcome results
None listed