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

2 augustus 2026 bijgewerkt door: Yue-Yin Pan, Anhui Provincial Cancer Hospital

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

107

Fase

  • Fase 4

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • China
    • Anhui
      • Hefei, Anhui, China, 230031
        • Werving
        • Anhui Cancer Hospital
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 5. 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.
  • 6. Major surgery within 28 days before the first study treatment without adequate recovery, or planned major surgery during the study.
  • 7. 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.
  • 8. 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.
  • 9. Inability or unwillingness to comply with protocol requirements, or any condition that, in the investigator's judgment, makes the participant unsuitable for study participation.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Cohort A: Advanced Squamous Non-Small Cell Lung Cancer(sqNSCLC)
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.
Geneesmiddel: Paclitaxel Oral Solution
  • 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.
Andere namen:
  • DHP107
  • Liporaxel
  • Oral paclitaxel
Geneesmiddel: PD-1/PD-L1 inhibitor (eg. Tislelizumab)
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.
Andere namen:
  • Pembrolizumab
  • Camrelizumab
  • Tislelizumab
  • Penpulimab
Experimenteel: Cohort B: Extensive-Stage Small Cell Lung Cancer(ES-SCLC)
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.
Geneesmiddel: Paclitaxel Oral Solution
  • 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.
Andere namen:
  • DHP107
  • Liporaxel
  • Oral paclitaxel
Geneesmiddel: PD-1/PD-L1 inhibitor (eg. Tislelizumab)
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.
Andere namen:
  • Pembrolizumab
  • Camrelizumab
  • Tislelizumab
  • Penpulimab

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Progression-Free Survival (PFS)
Tijdsspanne: First dose up to approximately 24 months
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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Objective Response Rate(ORR)
Tijdsspanne: First dose up to approximately 12 months
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.
First dose up to approximately 12 months
12-Week PFS rate
Tijdsspanne: 12 weeks
The proportion of participants who are alive and have not experienced radiographic disease progression at 12 weeks after initiation of maintenance treatment.
12 weeks
Disease Control Rate (DCR)
Tijdsspanne: First dose up to approximately 12 months
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
First dose up to approximately 12 months
Duration of Response (DoR)
Tijdsspanne: First dose up to approximately 12 months
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.
First dose up to approximately 12 months
Overall Survival (OS)
Tijdsspanne: First dose up to approximately 36 months
OS is defined as the time from the first oral paclitaxel administration to death from any cause.
First dose up to approximately 36 months
Incidence of Adverse Events (AE)
Tijdsspanne: First dose up to approximately 36 months
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.
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
Tijdsspanne: Baseline, Week 6, Week 12, Week 24, every 12 weeks thereafter, and at the end-of-treatment visit, assessed up to 36 months
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).
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
Tijdsspanne: Baseline and Weeks 6, 12, and 24, every 12 weeks thereafter, and at the end-of-treatment visit, up to 36 months
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).
Baseline and Weeks 6, 12, and 24, every 12 weeks thereafter, and at the end-of-treatment visit, up to 36 months

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percent Change From Baseline in Plasma Circulating Tumor DNA (ctDNA) Maximum Variant Allele Frequency (VAF) at Week 12
Tijdsspanne: Baseline and Week 12 (±14 days) after initiation of maintenance treatment

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

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.
Baseline and Week 12 (±14 days) after initiation of maintenance treatment
Change From Baseline in Neutrophil-to-Lymphocyte Ratio (NLR) at Week 12
Tijdsspanne: Baseline and Week 12 (±14 days) after initiation of maintenance treatment

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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Anhui Provincial Cancer Hospital

Onderzoekers

  • Hoofdonderzoeker: Yueyin Pan, MD, PhD, AnHui Provincial Cancer Hospital

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

24 juli 2026

Primaire voltooiing (Geschat)

1 juni 2029

Studie voltooiing (Geschat)

1 juni 2029

Studieregistratiedata

Eerst ingediend

29 juli 2026

Eerst ingediend dat voldeed aan de QC-criteria

2 augustus 2026

Eerst geplaatst (Werkelijk)

4 augustus 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

4 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

2 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2026-LLYJ-0070

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

ONBESLIST

Beschrijving IPD-plan

Individual participant-level data are not currently planned to be made publicly available. Aggregate study results may be presented at scientific meetings or published in peer-reviewed journals in accordance with applicable privacy, ethical, and institutional requirements.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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