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.
Immune checkpoint inhibitor-based chemoimmunotherapy is a standard first-line treatment for advanced squamous non-small cell lung cancer and extensive-stage small cell lung cancer. However, many patients experience disease progression shortly after completing the chemotherapy component and entering the maintenance phase. More effective and tolerable maintenance strategies are therefore needed. Metronomic chemotherapy uses relatively low doses of cytotoxic treatment administered repeatedly over time. In addition to direct antitumor activity, metronomic paclitaxel may modulate the tumor immune microenvironment and enhance the effects of immune checkpoint inhibition. An oral paclitaxel formulation may also be more suitable for long-term maintenance treatment than intravenous paclitaxel because it avoids repeated intravenous infusions. This is a prospective, open-label, multicenter, nonrandomized, multi-cohort exploratory study. Participants must have completed four cycles of standard first-line chemoimmunotherapy and achieved complete response, partial response, or stable disease without disease progression. Cohort A will enroll approximately 67 participants with advanced squamous non-small cell lung cancer(sqNSCLC). Cohort B will enroll approximately 40 participants with extensive-stage small cell lung cancer(ES-SCLC). Both cohorts will receive oral paclitaxel solution at 100 mg/m² per dose, administered orally three times weekly, together with a PD-1 or PD-L1 inhibitor administered every 3 weeks according to the approved or guideline-recommended regimen. The maintenance immune checkpoint inhibitor should generally remain the same as that used during induction therapy. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion. Tumor assessments will generally be performed every 6 weeks, and safety assessments will generally be performed every 3 weeks. The primary endpoint is progression-free survival measured from the first dose of oral paclitaxel. The two cohorts will be analyzed independently, and no formal efficacy comparison between the two cohorts is planned. Exploratory analyses will evaluate circulating tumor DNA, peripheral immune-cell subsets, inflammatory and immune-related factors, and PD-1/PD-L1-related biomarkers.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
107
* 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.
The 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.
Anhui Cancer Hospital
Hefei, Anhui, China
RECRUITINGProgression-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.
Time frame: First dose up to approximately 24 months
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.
Time frame: First dose up to approximately 12 months
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.
Time frame: 12 weeks
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
Time frame: First dose up to approximately 12 months
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.
Time frame: First dose up to approximately 12 months
Overall Survival (OS)
OS is defined as the time from the first oral paclitaxel administration to death from any cause.
Time frame: First dose up to approximately 36 months
Incidence of Adverse Events (AE)
The number and proportion of participants experiencing treatment-emergent AEs (TEAE), serious AEs (SAE), treatment-related AEs (TRAE), grade 3 or higher AEs (AE), and AEs resulting in treatment interruption, dose reduction, permanent treatment discontinuation, hospitalization, or death. AE will be graded according to the CTCAE 5.0.
Time frame: First dose up to approximately 36 months
Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score
EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998).
Time frame: Baseline, Week 6, Week 12, Week 24, every 12 weeks thereafter, and at the end-of-treatment visit, assessed up to 36 months
Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score
The EORTC QLQ-LC13 module incorporates one multiple item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998).
Time frame: Baseline and Weeks 6, 12, and 24, every 12 weeks thereafter, and at the end-of-treatment visit, up to 36 months
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