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

Sponsor
Sichuan Cancer Hospital and Research Institute
Study ID
NCT07775040
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Spatially Fractionated Radiotherapy (SFRT) — RADIATION
    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 — DRUG
    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 — DRUG
    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 — DRUG
    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 — DRUG
    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 — DRUG
    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 — PROCEDURE
    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 Details

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.

Key Dates

First listed
Aug 20, 2026
Start date
Aug 20, 2026
Status verified
Aug 2026
Primary completion
Jun 30, 2030
Completion
Jun 30, 2030

Study Design

Enrollment
43 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: SFRT + Tislelizumab + Chemotherapy
    Participants receive spatially fractionated radiotherapy (lattice radiation therapy) to the primary lung tumor, with a prescription dose of GTV 20 Gy in 5 fractions and GTV-Lattice 60 Gy in 5 fractions, delivered on Monday, Wednesday, and Friday over one week. Following SFRT, participants receive 2 to 4 cycles (depending on clinical evaluation and per protocol specifications) of tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle (Q3W), combined with platinum-based doublet chemotherapy (carboplatin AUC 5 or cisplatin 75 mg/m², plus pemetrexed 500 mg/m² for non-squamous histology or paclitaxel 175 mg/m² for squamous histology). Definitive radical surgery (lobectomy, bilobectomy, pneumonectomy, or sleeve resection with systematic mediastinal lymph node dissection) is performed 4 to 6 weeks (±7 days) after the last dose of neoadjuvant therapy. The first 6 enrolled patients undergo dose-limiting toxicity (DLT) assessment within 21 days after the first dose of study drugs.

Primary Outcome Measure

Major Pathological Response (MPR) Rate [ Time Frame: Assessed at the time of surgical resection, performed 4-6 weeks (±7 days) after the last dose of neoadjuvant therapy. ]

Central Contacts

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