A Multicenter, Open-Label, Single-Arm Phase I/II Study of Oral Paclitaxel Solution Combined With an Immune Checkpoint Inhibitor and Concurrent Stereotactic Body Radiotherapy as Neoadjuvant Treatment in Older Patients With Resectable Stage IIA-IIIB Non-Small Cell Lung Cancer
| Registry | NCT07754812 |
|---|---|
| Status | Recruiting |
| Phase | Phase 4 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 78 (Estimated) |
| Sponsor | Shanghai Pulmonary Hospital, Shanghai, China (Other) |
| Conditions | NSCLC (Non-small Cell Lung Cancer) |
| Interventions | Oral Paclitaxel Solution, PD-1/PD-L1 inhibitor, Stereotactic Body Radiotherapy (SBRT), Radical Lung Cancer Surgery (Drug, radiation, procedure) |
| Dates | start 2026-06-25, primary completion 2028-10-31 (estimated), completion 2028-10-31 (estimated), first posted 2026-08-10, last updated 2026-08-10 |
| Locations | 5 sites in China |
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All trials for NSCLC (Non-small Cell Lung Cancer) All trials of Oral Paclitaxel Solution All trials of PD-1/PD-L1 inhibitor
his multicenter, open-label, single-arm phase I/II trial will evaluate the safety, tolerability, and preliminary efficacy of oral paclitaxel solution combined with an immune checkpoint inhibitor and concurrent stereotactic body radiotherapy (SBRT) as neoadjuvant therapy in patients aged 70 years or older with resectable stage IIA-IIIB non-small cell lung cancer (NSCLC) without sensitizing EGFR, ALK, or ROS1 alterations.
In Phase I, a 3+3 dose-escalation design will evaluate oral paclitaxel at 80, 120, and 160 mg/m² administered orally on Days 1 and 8 of each cycle, divided into morning and evening doses, in combination with an investigator-selected anti-PD-1 or anti-PD-L1 monoclonal antibody and SBRT at 8 Gy in 3 fractions. Phase II will expand enrollment at the recommended Phase II dose (RP2D). The principal efficacy outcome is pathologic complete response after surgery. Other outcomes include major pathologic response, radiographic response, event-free survival, overall survival, surgical resection and R0 resection rates, and exploratory biomarker changes.
Older patients with NSCLC may have reduced organ reserve, more comorbidities, and a higher risk of toxicity from standard platinum-based chemotherapy, intensive radiotherapy, or multimodality treatment. The study is designed to explore a potentially lower-intensity neoadjuvant regimen that combines oral paclitaxel solution, immune checkpoint blockade, and precision radiotherapy.
Phase I will use a conventional 3+3 dose-escalation design. Oral paclitaxel solution will be evaluated at 80, 120, and 160 mg/m² on Days 1 and 8 of each cycle, administered in divided morning and evening doses. An anti-PD-1 or anti-PD-L1 monoclonal antibody will be selected by the investigator according to standard of care and administered according to the approved prescribing information. Concurrent SBRT will be delivered at 8 Gy per fraction for 3 fractions to the primary lung tumor and selected nodal regions. The Phase I objective is to evaluate safety and identify the RP2D.
Phase II will enroll additional participants at the RP2D to evaluate antitumor activity and feasibility. Participants who remain suitable for radical lung cancer surgery are intended to undergo resection after completion of neoadjuvant treatment. The study will assess pathologic response, radiographic response, surgical feasibility, event-free survival, overall survival, and changes in immune cell subsets, circulating tumor DNA, and PD-L1 expression.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Phase 1 Dose-Escalation Cohort | Experimental | Drug: Oral Paclitaxel Solution; Drug: PD-1/PD-L1 inhibitor; Radiation: Stereotactic Body Radiotherapy (SBRT); Procedure: Radical Lung Cancer Surgery | Participants enrolled in Phase 1 will receive oral paclitaxel solution in combination with an anti-PD-1 monoclonal antibody and stereotactic body radiation therapy (SBRT). Oral paclitaxel solution will be evaluated at sequential dose levels of 80 mg/m², 120 mg/m², and 160 mg/m² using a conventional 3+3 dose-escalation design. The primary objective of this cohort is to evaluate the safety and tolerability of the combination regimen and to determine the recommended Phase 2 dose (RP2D) of oral paclitaxel solution. Tumor response and surgical feasibility will be assessed after completion of the protocol-specified treatment. |
| Phase 2 Cohort A - Operable Cohort | Experimental | Drug: Oral Paclitaxel Solution; Drug: PD-1/PD-L1 inhibitor; Radiation: Stereotactic Body Radiotherapy (SBRT); Procedure: Radical Lung Cancer Surgery | Participants enrolled in Phase 2 Cohort A will be patients considered eligible for curative-intent surgery after multidisciplinary evaluation. Participants will receive oral paclitaxel solution at the RP2D established in Phase 1, in combination with an anti-PD-1 monoclonal antibody and SBRT. After completion of the protocol-specified neoadjuvant treatment, participants will undergo tumor response assessment and surgical evaluation. Participants who remain operable will proceed to curative-intent surgical resection. |
| Phase 2 Cohort B - Inoperable Cohort | Experimental | Drug: Oral Paclitaxel Solution; Drug: PD-1/PD-L1 inhibitor; Radiation: Stereotactic Body Radiotherapy (SBRT) | Participants enrolled in Phase 2 Cohort B will be patients considered unsuitable for curative-intent surgery after multidisciplinary evaluation. Participants will receive oral paclitaxel solution at the RP2D established in Phase 1, in combination with an anti-PD-1 monoclonal antibody and radiotherapy. Participants will receive protocol-specified non-surgical, definitive-intent treatment and will undergo radiographic tumor response assessment and long-term survival follow-up. |
Sex: All, ages: 70 Years to any
Inclusion Criteria: * Age 70 years or older, regardless of sex. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Histologically confirmed non-small cell lung cancer, clinical stage IIA-IIIB according to the 8th edition of the AJCC staging system. * No evidence of distant metastasis and considered suitable for radical lung cancer surgery. * The primary lung lesion is suitable for stereotactic body radiotherapy. * No sensitizing driver alterations in EGFR, ALK, ROS1, or other tested actionable genes. * Adequate major organ function, including all of the following: * Absolute neutrophil count at least 1.5 × 10\^9/L, platelet count at least 100 × 10\^9/L, and hemoglobin at least 9 g/dL. * Total bilirubin no more than 1.5 × the upper limit of normal; alanine aminotransferase and aspartate aminotransferase no more than 2.5 × the upper limit of normal. * Serum creatinine no more than 1.5 × the upper limit of normal or creatinine clearance at least 60 mL/min. * Urine protein less than 1+; if urine protein is 1+, 24-hour urine protein must be less than 500 mg. * Blood glucose within the normal range or stable glycemic control in participants with diabetes. * Baseline forced expiratory volume in 1 second (FEV1) at least 2 L; if FEV1 is less than 2 L, the predicted postoperative FEV1 must be greater than 800 mL as assessed by a thoracic surgeon. * No myocardial infarction within the previous year, no unstable angina, no symptomatic severe arrhythmia, and no cardiac insufficiency. * The participant has been fully informed and voluntarily provides written informed consent. Exclusion Criteria: * Prior lobectomy, thoracic radiotherapy, or systemic antitumor therapy. * Another concurrent malignancy or a history of another malignancy cured less than 5 years before enrollment, except adequately treated cervical carcinoma in situ or basal cell or squamous cell carcinoma of the skin. * Active autoimmune disease or a history of autoimmune disease requiring systemic immunosuppressive treatment. * Active infection requiring systemic treatment, active tuberculosis, human immunodeficiency virus infection, active hepatitis B or hepatitis C, active syphilis, or another active transmissible infection specified by the protocol. * Severe cardiac, hepatic, renal, or metabolic disease that precludes surgery or study treatment. * History of interstitial lung disease or drug-induced pneumonitis, or imaging evidence of active interstitial lung disease. * Uncontrolled large pleural effusion or pericardial effusion. * Major surgery, severe trauma, or treatment with another investigational drug within 4 weeks before enrollment. * Recent receipt of an anticancer vaccine or live vaccine. * Any other condition that, in the investigator's opinion, makes the participant unsuitable for the study or may interfere with interpretation of the study results.
| Facility | City | Country | Status |
|---|---|---|---|
| Guangdong Provincial People's Hospital | Guangzhou, Guangdong | China | Not yet recruiting |
| The Affiliated Suqian Hospital of Xuzhou Medical University | Suqian, Jiangsu | China | Not yet recruiting |
| Shanghai Pulmonary Hospital | Shanghai, Shanghai Municipality | China | Recruiting |
| Zhejiang Cancer Hospital | Hangzhou, Zhejiang | China | Not yet recruiting |
| Lishui People's Hospital | Lishui, Zhejiang | China | Not yet recruiting |