Spatially Fractionated Radiotherapy With Tislelizumab and Chemotherapy for Bulky Stage III NSCLC: A Phase II Trial

NCT07775040 · tracked via the Priya Life Science China tracker

Sponsor

Sichuan Cancer Hospital and Research Institute

Phase

Phase 2

Started

2026-08-20

Last updated

2026-08-20

Condition(s) studied

Non-Small Cell Lung Cancer

Investigational drug(s) / intervention(s)

Spatially Fractionated Radiotherapy (SFRT)TislelizumabCarboplatinCisplatinPemetrexedPaclitaxelRadical Lung Resection Surgery

Spatially Fractionated Radiotherapy (SFRT): Participants receive lattice radiation therapy to the primary lung tumor. The gross tumor volume (GTV) is delineated, and lattice target volumes (GTV-Lattice) are generated using a hexagonal close-packed model within the tumor. Volumetric modulated arc therapy (VMAT) plans are designed. Prescription dose: GTV receives 20 Gy in 5 fractions, and GTV-Lattice receives 60 Gy in 5 fractions. After plan verification, treatment is delivered on 3 non-consecutive working days (e.g., Monday, Wednesday, Friday).

Tislelizumab: 200 mg administered via intravenous infusion on Day 1 of each 21-day cycle (Q3W) for 2 to 4 cycles, starting on Day 8-15 following SFRT.

Carboplatin: AUC 5 administered via intravenous infusion on Day 1 of each 21-day cycle (Q3W) for 2 to 4 cycles. Used in combination with either pemetrexed (for non-squamous histology) or paclitaxel (for squamous histology), at the investigator's discretion.

Cisplatin: 75 mg/m² administered via intravenous infusion on Day 1 of each 21-day cycle (Q3W) for 2 to 4 cycles. Used in combination with either pemetrexed (for non-squamous histology) or paclitaxel (for squamous histology), at the investigator's discretion. Adequate hydration and antiemetic prophylaxis are required.

Pemetrexed: 500 mg/m² administered via intravenous infusion on Day 1 of each 21-day cycle (Q3W) for 2 to 4 cycles. Indicated only for patients with non-squamous NSCLC. Vitamin B12 and folic acid supplementation are required per standard practice.

Paclitaxel: 175 mg/m² administered via intravenous infusion on Day 1 of each 21-day cycle (Q3W) for 2 to 4 cycles. Indicated only for patients with squamous NSCLC. Premedication to prevent hypersensitivity is required per standard practice.

Radical Lung Resection Surgery: Definitive radical surgery is performed 4 to 6 weeks (±7 days) after the last dose of neoadjuvant therapy. Surgical approaches include minimally invasive techniques (video-assisted thoracoscopic surgery \[VATS\] or robotic-assisted surgery) or open thoracotomy. Procedures include lobectomy, bilobectomy, pneumonectomy, or sleeve resection, combined with ipsilateral systematic mediastinal lymph node dissection.

Study summary

This is a prospective, single-arm, multicenter phase II clinical study evaluating the efficacy and safety of spatially fractionated radiotherapy (SFRT) combined with tislelizumab and platinum-based doublet chemotherapy as induction/conversion therapy for patients with potentially resectable stage III non-small cell lung cancer (NSCLC) with bulky disease (primary tumor \>5 cm).

SFRT, also known as lattice radiation therapy, is a novel radiotherapy technique that creates alternating high-dose and low-dose regions within the tumor. This approach not only reduces tumor burden but also may enhance anti-tumor immune responses, potentially working synergistically with immunotherapy.

Study participants will receive SFRT to the primary lung tumor (GTV 20 Gy/5 fractions, GTV-Lattice 60 Gy/5 fractions), followed by 2-4 cycles of tislelizumab (200 mg, Q3W) combined with platinum-based doublet chemotherapy. Surgery will be performed 4-6 weeks after the last cycle of neoadjuvant therapy. The first 6 enrolled patients will undergo dose-limiting toxicity (DLT) assessment within 21 days after the first dose of study drug.

The primary endpoint is major pathological response (MPR) rate, defined as the proportion of patients with ≤10% viable tumor cells in the resected specimen. Secondary endpoints include 1-year event-free survival (EFS), pathological complete response (pCR) rate, objective response rate (ORR), disease control rate (DCR), R0 resection rate, 1-year overall survival (OS), time to distant metastasis (TTDM), and safety.

A total of 44 patients will be enrolled across multiple centers in China. An interim analysis will be conducted after 50% of patients are enrolled.

Eligibility

Sex

ALL

Min age

18 Years

Max age

75 Years

Healthy volunteers

Inclusion Criteria: * Voluntary agreement to participate and signed written informed consent. * Cytologically or histologically confirmed (via percutaneous lung biopsy, bronchoscopy, mediastinoscopy, etc.) bulky stage III non-small cell lung cancer (NSCLC) per AJCC 9th edition staging, with primary tumor \>5 cm (T3-T4), N0-N2, and no prior chemotherapy, radiotherapy, surgery, or immunotherapy. * Pulmonary lesion considered potentially resectable by a multidisciplinary team (MDT) including a thoracic surgeon. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. * Adequate hematologic and organ function as demonstrated by: Absolute neutrophil count ≥ 1,500 × 10⁹/L. Platelet count ≥ 100 × 10⁹/L. Hemoglobin \> 9.0 g/dL. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min. AST/ALT ≤ 3 × ULN. Total bilirubin ≤ 1.5 × ULN. FEV1 ≥ 1.2 L or \> 40% of predicted value. INR/APTT within normal limits. -Age 18 to 75 years (inclusive). Exclusion Criteria: * Has or is suspected of having an autoimmune disease. Note: patients with vitiligo, type I diabetes mellitus, or hypothyroidism (Hashimoto's thyroiditis) requiring only hormone replacement therapy may be enrolled if no significant signs of recurrence are present. * Requires systemic corticosteroid therapy (\>10 mg prednisone or equivalent per day) or other immunosuppressive agents within 14 days after enrollment. Note: inhaled or topical corticosteroids, or adrenal hormone replacement therapy (\>10 mg prednisone or equivalent per day) for patients without active autoimmune disease, are permitted. * Prior history of thoracic radiotherapy. * Active bleeding prior to treatment. * Severe cardiac, pulmonary, hepatic, renal, or hematopoietic dysfunction, cachexia, or any condition that would preclude tolerance to radiochemotherapy. * History of diabetes mellitus for \>10 years with poorly controlled blood glucose. * History of interstitial lung disease or non-infectious pneumonitis. * NSCLC with known EGFR-sensitizing mutations, ALK fusion gene, or ROS1 rearrangement. * History of another malignancy (excluding non-melanoma skin cancer and carcinoma in situ of the bladder, stomach, colon, endometrium, cervix, melanoma, or breast) unless the malignancy has been in complete remission for ≥2 years and no additional anti-tumor therapy is required during the study period. * In the investigator's opinion, medically, psychologically, or physically unable to complete the study or to understand the patient information. * Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or other agents targeting T-cell co-stimulation or immune checkpoint pathways. * Active hepatitis B (HBV DNA ≥ 2000 IU/mL or ≥ 10⁴ copies/mL) or hepatitis C (anti-HCV antibody positive and HCV-RNA above the lower limit of detection). * HIV-positive or diagnosed with acquired immunodeficiency syndrome (AIDS). * Known or suspected allergy to the study drugs or to any agent used in this trial. * Pregnant or breastfeeding women.

Primary outcome measure(s)

Major Pathological Response (MPR) Rate — Assessed at the time of surgical resection, performed 4-6 weeks (±7 days) after the last dose of neoadjuvant therapy.
MPR is defined as the proportion of participants with ≤10% viable tumor cells remaining in the resected primary tumor specimen. Assessment method: based on the longest diameter (a cm) of the gross tumor, at least one pathological section per cm is stained with H\&E; the percentages of viable tumor cells, necrosis, stroma, and inflammatory cells are calculated for each section, and the average percentage of viable tumor cells is derived. MPR is achieved when this average is ≤10%.

Trial sites (1)

Facility	City	Region	Status
Sichuan Cancer Hospital	Chengdu	Sichuan

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07775040 on ClinicalTrials.gov ↗ ← All trials in China