Oral Paclitaxel Solution With Immunotherapy and Concurrent SBRT as Neoadjuvant Treatment for Older Adults With NSCLC

NCT07754812 | Recruiting Phase 4

• 1 other identifier: K26-560
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

NSCLC (Non-small Cell Lung Cancer)

Keywords

Elderly patients; Neoadjuvant therapy; Oral paclitaxel solution; Immune checkpoint inhibitor; SBRT; Resectable NSCLC; Pathologic complete response

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR) Rate in Phase 2

  The percentage of participants in the Phase 2 operable cohort who achieve a CR according to RECIST v1.1, at the protocol-specified preoperative tumor assessment. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes must have a reduction in the short axis to less than 10 mm. Participants who discontinue treatment, experience disease progression, become unable to undergo the planned response assessment, or have no evaluable post-baseline tumor assessment will be classified as not having achieved a CR.

  2 weeks (±14 days) after surgery or radical radiotherapy

• Incidence of Grade 3 or Higher Treatment-Related Adverse Events (TRAE) in Phase 1

  The percentage of participants in the Phase 1 dose-escalation cohort who experience at least one Grade 3 or higher TRAE during the safety assessment period. Adverse events will be graded according to the CTCAE 5.0. The relationship of each adverse event (AE) to oral paclitaxel solution, the anti-PD-1 antibody, radiotherapy, or the combination regimen will be assessed by the investigator.

  First dose up to 1 week (±7 days) after neoadjuvant therapy

Secondary Outcomes (4)

• CR Rate in Phase 1

  2 weeks (±14 days) after surgery

• Two-Year Event-Free Survival (EFS) Rate

  2 years

• Two-Year Overall Survival (OS) Rate

  2 years

• Incidence of AE

  First dose up to 1 week (±7 days) after neoadjuvant therapy

Other Outcomes (3)

• Change From Baseline in Circulating Tumor DNA (ctDNA)

  At baseline, and 1 week (±7days) after completion of neoadjuvant therapy,

• Change From Baseline in PD-L1 Expression

  At baseline, and 1 week (±7days) after completion of neoadjuvant therapy,

• Change From Baseline in Tumor and Peripheral Immune Cell Subsets

  At baseline, and 1 week (±7days) after completion of neoadjuvant therapy,

Study Arms (3)

Phase 1 Dose-Escalation Cohort

EXPERIMENTAL

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.

Drug: Oral Paclitaxel Solution; Drug: PD-1/PD-L1 inhibitor; Radiation: Stereotactic Body Radiotherapy (SBRT); Procedure: Radical Lung Cancer Surgery

Phase 2 Cohort A - Operable Cohort

EXPERIMENTAL

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.

Drug: Oral Paclitaxel Solution; Drug: PD-1/PD-L1 inhibitor; Radiation: Stereotactic Body Radiotherapy (SBRT); Procedure: Radical Lung Cancer Surgery

Phase 2 Cohort B - Inoperable Cohort

EXPERIMENTAL

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.

Drug: Oral Paclitaxel Solution; Drug: PD-1/PD-L1 inhibitor; Radiation: Stereotactic Body Radiotherapy (SBRT)

Interventions

PD-1/PD-L1 inhibitor DRUG

An PD-1/PD-L1 inhibitor selected by the investigator according to standard of care and administered according to the approved prescribing information

Phase 1 Dose-Escalation Cohort; Phase 2 Cohort A - Operable Cohort; Phase 2 Cohort B - Inoperable Cohort

Radical Lung Cancer Surgery PROCEDURE

Participants considered operable after neoadjuvant therapy are intended to undergo radical lung cancer surgery.

Phase 1 Dose-Escalation Cohort; Phase 2 Cohort A - Operable Cohort

Oral Paclitaxel Solution DRUG

Phase I dose levels: 80 mg/m², 120 mg/m², and 160 mg/m², administered orally on Days 1 and 8 of each cycle in divided morning and evening doses. Phase II: oral paclitaxel solution at the RP2D.

Also known as: Oral paclitaxel, Liporaxel, DHP107

Phase 1 Dose-Escalation Cohort; Phase 2 Cohort A - Operable Cohort; Phase 2 Cohort B - Inoperable Cohort

Stereotactic Body Radiotherapy (SBRT) RADIATION

SBRT at 8 Gy per fraction for 3 fractions to the primary lung tumor and selected lymph node regions.

Phase 1 Dose-Escalation Cohort; Phase 2 Cohort A - Operable Cohort; Phase 2 Cohort B - Inoperable Cohort

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (5)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 519041, China

NOT YET RECRUITING

The Affiliated Suqian Hospital of Xuzhou Medical University

Suqian, Jiangsu, 223800, China

NOT YET RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

NOT YET RECRUITING

Lishui People's Hospital

Lishui, Zhejiang, 323000, China

NOT YET RECRUITING

Related Publications (7)

• Jabbour SK, Lee KH, Frost N, Breder V, Kowalski DM, Pollock T, Levchenko E, Reguart N, Martinez-Marti A, Houghton B, Paoli JB, Safina S, Park K, Komiya T, Sanford A, Boolell V, Liu H, Samkari A, Keller SM, Reck M. Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. JAMA Oncol. 2021 Jun 4;7(9):1-9. doi: 10.1001/jamaoncol.2021.2301. Online ahead of print.

  PMID: 34086039 RESULT

• Zhao ZR, Liu SL, Zhou T, Chen G, Long H, Su XD, Zhang X, Fu JH, Lin P, Zhang LJ, Rong TH, Wu JD, Li ZC, Su HL, Chen JY, Yang YP, Lin YB, Xi M, Yang H. Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial. Lancet Respir Med. 2024 Dec;12(12):988-996. doi: 10.1016/S2213-2600(24)00215-7. Epub 2024 Sep 18.

  PMID: 39305910 RESULT

• Liu J, Huang X, Yang Y, Lv W, Wang Y, Xia P, Hu J. Comparison of efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA-IIIB non-small-cell lung cancer in real-world practice. BMC Pulm Med. 2024 Nov 29;24(1):592. doi: 10.1186/s12890-024-03417-8.

  PMID: 39614293 RESULT

• Sorin M, Prosty C, Ghaleb L, Nie K, Katergi K, Shahzad MH, Dube LR, Atallah A, Swaby A, Dankner M, Crump T, Walsh LA, Fiset PO, Sepesi B, Forde PM, Cascone T, Provencio M, Spicer JD. Neoadjuvant Chemoimmunotherapy for NSCLC: A Systematic Review and Meta-Analysis. JAMA Oncol. 2024 May 1;10(5):621-633. doi: 10.1001/jamaoncol.2024.0057.

  PMID: 38512301 RESULT

• Chang JY, Lin SH, Dong W, Liao Z, Gandhi SJ, Gay CM, Zhang J, Chun SG, Elamin YY, Fossella FV, Blumenschein G, Cascone T, Le X, Pozadzides JV, Tsao A, Verma V, Welsh JW, Chen AB, Altan M, Mehran RJ, Vaporciyan AA, Swisher SG, Balter PA, Fujimoto J, Wistuba II, Feng L, Lee JJ, Heymach JV. Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet. 2023 Sep 9;402(10405):871-881. doi: 10.1016/S0140-6736(23)01384-3. Epub 2023 Jul 18.

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• Theelen WSME, Chen D, Verma V, Hobbs BP, Peulen HMU, Aerts JGJV, Bahce I, Niemeijer ALN, Chang JY, de Groot PM, Nguyen QN, Comeaux NI, Simon GR, Skoulidis F, Lin SH, He K, Patel R, Heymach J, Baas P, Welsh JW. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2021 May;9(5):467-475. doi: 10.1016/S2213-2600(20)30391-X. Epub 2020 Oct 20.

  PMID: 33096027 RESULT

• Verma S, Breadner D, Mittal A, Palma DA, Nayak R, Raphael J, Vincent M. An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy. Cancers (Basel). 2024 Mar 27;16(7):1302. doi: 10.3390/cancers16071302.

  PMID: 38610980 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Pathologic Complete Response

Interventions

Paclitaxel; Immune Checkpoint Inhibitors; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Xiaoling Xu, MD, PhD

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoling Xu, MD, PhD

CONTACT

+86-21-65115006; xuxl@zjcc.org.cn

Study Design

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

Model Details: Phase I uses a 3+3 dose-escalation design to determine the recommended Phase II dose of oral paclitaxel solution in combination with an immune checkpoint inhibitor and concurrent SBRT. Phase II is a single-arm expansion at the recommended Phase II dose to evaluate efficacy and feasibility.

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 10, 2026
• Study Start: June 25, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: August 10, 2026

Record last verified: 2026-08

Locations

CN (5)