Efficacy and Safety of Metronomic Oral Paclitaxel Plus an Immune Checkpoint Inhibitor as Maintenance Therapy After First-Line Induction in Advanced Squamous Non-Small Cell Lung Cancer and Extensive-Stage Small Cell Lung Cancer: A Multicenter, Multi-Cohort Exploratory Study
This study will evaluate the efficacy and safety of metronomic oral paclitaxel combined with a PD-1 or PD-L1 inhibitor as maintenance therapy in patients with advanced lung cancer whose disease has not progressed after first-line chemoimmunotherapy. The study will include two independently analyzed cohorts. Cohort A will include patients with advanced squamous non-small cell lung cancer(sqNSCLC), and Cohort B will include patients with extensive-stage small cell lung cancer(ES-SCLC). All participants will receive oral paclitaxel three times weekly together with the same immune checkpoint inhibitor used during first-line induction therapy, whenever feasible. The primary outcome is progression-free survival. Other outcomes include tumor response, overall survival, adverse events, treatment tolerability, and quality of life. Approximately 107 participants will be enrolled across multiple study centers.
• 1\. The participant has been fully informed about the study, voluntarily agrees to participate, provides written informed consent, and is willing to comply with long-term follow-up and study medication management.
• 2\. Age 18 to 75 years, inclusive.
• 3\. The participant meets the disease-specific requirements for either Cohort A or Cohort B: - Cohort A: Histologically and/or cytologically confirmed squamous non-small cell lung cancer(sqNSCLC), clinical stage IIIB to IV, unresectable and not suitable for definitive chemoradiotherapy, without actionable driver-gene alterations, and treatment-naive before initiation of first-line induction therapy. - Cohort B: Histologically and/or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC), defined according to the eighth edition of the American Joint Committee on Cancer staging system as stage IV disease, including any T, any N, and M1a, M1b, or M1c disease, or T3 to T4 disease due to multiple pulmonary nodules or disease that is too extensive or bulky to be included within a tolerable definitive radiotherapy field.
• 4\. The participant has completed the required first-line induction regimen: - Cohort A: Completion of four cycles of a PD-1 or PD-L1 inhibitor plus cisplatin or carboplatin and paclitaxel or nab-paclitaxel, with a best induction response of complete response (CR), partial response (PR), or stable disease (SD) and no evidence of disease progression. - Cohort B: Completion of four cycles of a PD-1 or PD-L1 inhibitor plus cisplatin or carboplatin and etoposide, with a best induction response of CR, PR, or SD and no evidence of disease progression.
• 5\. The last dose of first-line induction treatment was administered no more than 28 days before the first study treatment.
• 6\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 7\. Estimated life expectancy of at least 3 months.
• 8\. Adequate bone marrow and organ function, including: - Absolute neutrophil count (ANC) of at least 1.5 × 10⁹/L, platelet count of at least 100 × 10⁹/L, and hemoglobin of at least 90 g/L, without blood transfusion, growth-factor support, or erythropoietin within 14 days before assessment. - International normalized ratio (INR) and/or prothrombin time (PT) no greater than 1.5 times the upper limit of normal (ULN), and activated partial thromboplastin time (APTT) no greater than 1.5 times ULN. Participants receiving anticoagulation are eligible if coagulation parameters are within the expected therapeutic range.- Total serum bilirubin no greater than 1.5 times ULN; for participants with Gilbert syndrome, total bilirubin no greater than 3 times ULN. - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) no greater than 2.5 times ULN, or no greater than 5 times ULN in participants with documented liver metastases.- Serum creatinine no greater than 1.5 times ULN and creatinine clearance of at least 60 mL/min for participants who received cisplatin or greater than 45 mL/min for participants who received carboplatin, calculated using the Cockcroft-Gault formula. - Serum amylase and/or lipase no greater than 1.5 times ULN.
• 9\. At least one measurable lesion according to RECIST v1.1 before initiation of first-line induction therapy. Participants who achieve a CR and have no measurable lesion at maintenance-study entry remain eligible for progression-free survival (PFS) follow-up.
• 10\. Participants with central nervous system (CNS) metastases may be enrolled if previous CNS metastases have received local treatment with surgery and/or radiotherapy at least 2 weeks before enrollment, neurological symptoms are absent or stable, and treatment-related adverse events have recovered to grade 1 or lower. Participants should not require ongoing antiepileptic treatment. If corticosteroids are clinically required, the dose must be stable and no greater than 10 mg/day prednisone or equivalent.
• 11\. Participants of reproductive potential must agree to use an effective method of contraception during the study and for at least 3 months after the last study treatment. Women of childbearing potential must have a negative serum or urine pregnancy test before enrollment.