Metronomic Oral Paclitaxel Plus PD-1/ PD-L1 Inhibitor Maintenance in Advanced Lung Cancer (PULSE Study)

NCT07744698 | Recruiting Phase 4

• 1 other identifier: 2026-LLYJ-0070
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Squamous Non-Small Cell Lung Cancer sqNSCLC; Extensive-stage Small Cell Lung Cancer (ES-SCLC)

Keywords

Oral paclitaxel; Metronomic chemotherapy; Maintenance therapy; Immune checkpoint inhibitor; PD-1 inhibitor; PD-L1 inhibitor; sqNSCLC; ES-SCLC; Chemoimmunotherapy; First-line maintenance therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  First dose up to approximately 24 months

Secondary Outcomes (8)

• Objective Response Rate(ORR)

  First dose up to approximately 12 months

• 12-Week PFS rate

  12 weeks

• Disease Control Rate (DCR)

  First dose up to approximately 12 months

• Duration of Response (DoR)

  First dose up to approximately 12 months

• Overall Survival (OS)

  First dose up to approximately 36 months

Other Outcomes (3)

• Percent Change From Baseline in Plasma Circulating Tumor DNA (ctDNA) Maximum Variant Allele Frequency (VAF) at Week 12

  Baseline and Week 12 (±14 days) after initiation of maintenance treatment

• Change From Baseline in Tumor Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) at Week 12

  Baseline and Week 12 (±14 days) after initiation of maintenance treatment

• Change From Baseline in Neutrophil-to-Lymphocyte Ratio (NLR) at Week 12

  Baseline and Week 12 (±14 days) after initiation of maintenance treatment

Study Arms (2)

Cohort A: Advanced Squamous Non-Small Cell Lung Cancer(sqNSCLC)

EXPERIMENTAL

Participants with histologically or cytologically confirmed, unresectable stage IIIB to IV squamous non-small cell lung cancer(sqNSCLC) who are not candidates for definitive chemoradiotherapy and who have completed four cycles of first-line treatment with a PD-1 or PD-L1 inhibitor, a platinum agent, and paclitaxel or nab-paclitaxel without disease progression will receive metronomic oral paclitaxel plus maintenance immune checkpoint inhibition.

Drug: Paclitaxel Oral Solution; Drug: PD-1/PD-L1 inhibitor (eg. Tislelizumab)

Cohort B: Extensive-Stage Small Cell Lung Cancer(ES-SCLC)

EXPERIMENTAL

Participants with histologically or cytologically confirmed extensive-stage small cell lung cancer(ES-SCLC) who have completed four cycles of first-line treatment with a PD-1 or PD-L1 inhibitor, a platinum agent, and etoposide without disease progression will receive metronomic oral paclitaxel plus maintenance immune checkpoint inhibition.

Drug: Paclitaxel Oral Solution; Drug: PD-1/PD-L1 inhibitor (eg. Tislelizumab)

Interventions

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.

Also known as: Oral paclitaxel, Liporaxel, DHP107

Cohort A: Advanced Squamous Non-Small Cell Lung Cancer(sqNSCLC); Cohort B: Extensive-Stage Small Cell Lung Cancer(ES-SCLC)

PD-1/PD-L1 inhibitor (eg. Tislelizumab) DRUG

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.

Also known as: Tislelizumab, Pembrolizumab, Camrelizumab, Penpulimab

Cohort A: Advanced Squamous Non-Small Cell Lung Cancer(sqNSCLC); Cohort B: Extensive-Stage Small Cell Lung Cancer(ES-SCLC)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. Age 18 to 75 years, inclusive.
• \. 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.
• \. 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.
• \. The last dose of first-line induction treatment was administered no more than 28 days before the first study treatment.
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• \. Estimated life expectancy of at least 3 months.
• \. 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.
• \. 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.
• \. 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.
• \. 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.

You may not qualify if:

• \. Known hypersensitivity to oral paclitaxel, an immune checkpoint inhibitor, or any component of the study drugs.
• \. Requirement for long-term treatment with a strong P-glycoprotein inhibitor that cannot be discontinued during the study.
• \. 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.
• \. Any of the following during previous immune checkpoint inhibitor (ICI) treatment: - Immune-related pneumonitis, immune-related myocarditis, or immune-related neurological toxicity of any grade. - Other grade 3 or higher immune-related adverse events (irAE) that have not recovered to grade 1 or lower or to baseline. - Grade 3 or higher irAE during first-line induction that have not recovered to grade 1 or lower or to baseline. - Permanent discontinuation of the ICI because of immune-related toxicity.
• \. Major surgery within 28 days before the first study treatment without adequate recovery, or planned major surgery during the study.
• \. Active hepatitis, active tuberculosis, or another serious infection requiring systemic treatment, including active hepatitis C virus (HCV) infection, except for participants who are HCV antibody-positive but RNA-negative; active hepatitis B virus (HBV) infection with positive HBV surface antigen and HBV DNA greater than 2,000 IU/mL; bacteremia; or severe infectious pneumonia.
• \. Uncontrolled or serious cardiovascular disease, including: - Myocardial infarction, unstable angina, congestive heart failure of New York Heart Association class 2 or higher, or another serious cardiac disorder within 6 months before the first study treatment. - A clinically significant electrocardiographic (ECG) abnormality, including clinically significant arrhythmia or corrected QT interval greater than 450 milliseconds.- Left ventricular ejection fraction below 50% on echocardiography.
• \. Inability or unwillingness to comply with protocol requirements, or any condition that, in the investigator's judgment, makes the participant unsuitable for study participation.

Sponsors & Collaborators

• Anhui Provincial Cancer Hospital: lead

Study Sites (1)

Anhui Cancer Hospital

Hefei, Anhui, 230031, China

RECRUITING

Related Publications (13)

• Jin Li et al. Paclitaxel oral solution versus paclitaxel injection as second-line therapy in advanced gastric cancer: A randomized, open-label, non-inferiority phase 3 trial.JCO 42, 4051-4051(2024).

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• Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

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MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Paclitaxel; tislelizumab; pembrolizumab; camrelizumab; penpulimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Yueyin Pan, MD, PhD

  Anhui Provincial Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tian Tian, MD, PhD

CONTACT

+86-0551-65327751; drtiantian@ustc.edu.cn

Yueyin Pan, MD, PhD

CONTACT

+86-0551-65327751; panyueyin@ustc.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Department of Oncology

Model Details: Participants will be assigned to one of two disease-specific cohorts according to tumor histology. Cohort A will include participants with advanced squamous non-small cell lung cancer(sqNSCLC), and Cohort B will include participants with extensive-stage small cell lung cancer(ES-SCLC). Both cohorts will receive the same maintenance strategy of metronomic oral paclitaxel plus a PD-1 or PD-L1 inhibitor. The cohorts will be analyzed independently, with no formal between-cohort efficacy comparison.

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 4, 2026
• Study Start: July 24, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: August 4, 2026

Record last verified: 2026-08

Locations

CN (1)