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.
1. Known hypersensitivity to oral paclitaxel, an immune checkpoint inhibitor, or any component of the study drugs.
2. Requirement for long-term treatment with a strong P-glycoprotein inhibitor that cannot be discontinued during the study.
3. A gastrointestinal disorder within 6 months before the first study treatment that may substantially interfere with oral drug absorption, including complete intestinal obstruction. Previous gastrectomy alone is not an exclusion criterion.
4. Active autoimmune disease or a history of autoimmune disease, including but not limited to interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, or nephritis. Participants with vitiligo, well-controlled type 1 diabetes mellitus, or hypothyroidism requiring only hormone-replacement therapy may be enrolled.
Parallel
Paclitaxel Oral Solution
Drug* Paclitaxel oral solution will be administered orally at 100 mg/m² per dose three times weekly, on Monday, Wednesday, and Friday, approximately 1 hour after a meal. * For Paclitaxel oral solution, treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion. If dose reduction is required, the first reduced dose level will be 75 mg/m² per dose and the second reduced dose level will be 50 mg/m² per dose. Once the dose has been reduced, dose re-escalation will not be permitted.
PD-1/PD-L1 inhibitor (eg. Tislelizumab)
DrugThe appropriate PD-1/PD-L1 inhibitor will be selected by the investigator based on the patient's specific condition, eg. Tislelizumab, Pembrolizumab, Camrelizumab and Penpulimab, and its administration will strictly follow the dosing instructions provided in the relevant drug's package insert. The maintenance PD-1/PD-L1 inhibitor should generally be the same agent used during first-line induction treatment.
Progression-Free Survival (PFS)
PFS is defined as the time from the date of the first oral paclitaxel administration to the first occurrence of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurred first.
Objective Response Rate(ORR)
ORR is defined as the proportion of participants whose best overall response during maintenance treatment is a complete response (CR) or partial response (PR) as determined by the investigator using RECIST v1.1.
12-Week PFS rate
The proportion of participants who are alive and have not experienced radiographic disease progression at 12 weeks after initiation of maintenance treatment.
Disease Control Rate (DCR)
DCR is defined as the proportion of participants whose best overall response during maintenance treatment is CR, PR or stable disease (SD) according to RECIST v1.1
Duration of Response (DoR)
DoR is defined for participants who achieve a CR or PR as the time from the first documented objective response to radiographic disease progression or death from any cause, whichever occurs first.
Percent Change From Baseline in Plasma Circulating Tumor DNA (ctDNA) Maximum Variant Allele Frequency (VAF) at Week 12
Plasma ctDNA will be assessed using paired blood samples collected at baseline and at Week 12 after initiation of maintenance treatment using the same prespecified next-generation sequencing panel. Among participants with at least one tumor-associated variant detectable at baseline, the maximum VAF among the baseline-tracked variants will be reported as a percentage at both time points. Percent change from baseline will be calculated as: \[(Week 12 maximum VAF - baseline maximum variant allele frequency) / baseline maximum VAF\] × 100. Negative values indicate a reduction in molecular tumor burden, whereas positive values indicate an increase.
Change From Baseline in Tumor Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) at Week 12
Tumor PD-L1 expression will be assessed in paired tumor tissue samples collected at baseline and at Week 12 after initiation of maintenance treatment using the same validated immunohistochemistry (IHC) assay. PD-L1 expression will be reported as the tumor proportion score, defined as the percentage of viable tumor cells showing partial or complete membranous staining. The TPS ranges from 0% to 100%. Change from baseline will be calculated in percentage points as the Week 12 tumor proportion score minus the baseline tumor proportion score. Positive values indicate increased PD-L1 expression. This exploratory assessment will be performed in participants with evaluable paired tumor tissue samples. Post-treatment PD-L1 testing is optional for participants in Cohort B.This assessment will be performed only in participants with evaluable paired tumor tissue samples.
Change From Baseline in Neutrophil-to-Lymphocyte Ratio (NLR) at Week 12
The NLR will be calculated by dividing the absolute neutrophil count by the absolute lymphocyte count obtained from the same complete blood count assessment. The NLR is unitless. Change from baseline will be calculated as the Week 12 NLR minus the baseline NLR ratio. Positive values indicate an increase in the NLR.
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