A Phase 2 interventional study of Quad Shot Radiotherapy and Tislelizumab in Non-Small Cell Lung Cancer, sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Phase 2, Interventional, and Treatment
This study aims to evaluate a new pre-surgery (neoadjuvant) treatment for patients with stage II-III non-small cell lung cancer (NSCLC). Currently, standard pre-surgery treatment involves immunotherapy combined with chemotherapy. While effective, many patients still have residual tumor cells after this standard treatment.
Radiation therapy can not only kill tumor cells but also help the immune system recognize and fight cancer. The type of radiation used in this study is called "Quad Shot" (QS) radiotherapy. It is a short, high-dose, cyclical treatment designed to boost the effects of immunotherapy with less toxicity than standard daily radiation.
Patients in this study will receive 3 cycles of QS radiotherapy combined with Tislelizumab (an immunotherapy drug) and standard platinum-based chemotherapy before surgery. The main goal of this study is to see if this combined approach can make the tumor completely disappear under a microscope (called pathological complete response, or pCR). Researchers will also monitor the safety of the treatment, side effects, and how well patients tolerate the treatment before undergoing surgery. Approximately 12 patients will be enrolled in this study.
Background:
Neoadjuvant immune checkpoint inhibitor (ICI) combined with platinum-based chemotherapy has become a standard of care for resectable stage II-III NSCLC, as demonstrated by phase III trials such as CheckMate-816, KEYNOTE-671, and RATIONALE-315. However, a significant proportion of patients still fail to achieve deep pathological responses due to mechanisms such as poor antigen release, impaired antigen presentation, and an immunosuppressive tumor microenvironment (TME).
Radiotherapy possesses immunomodulatory properties, inducing immunogenic cell death and promoting antigen release. However, traditional continuous fractionated radiotherapy may deplete circulating lymphocytes and cause normal tissue damage. The "Quad Shot" (QS) regimen is a cyclical hypofractionated radiotherapy approach (14-14.8 Gy in 4 fractions over 2 days) that has shown low toxicity in palliative settings. Its cyclical, pulsatile nature may provide repeated immune stimulation and TME remodeling, making it a promising partner for immunotherapy.
Study Design:
This is a single-arm, prospective, exploratory phase II clinical study. Patients with histologically or cytologically confirmed, untreated, resectable stage II-IIIB NSCLC (including T3-4N2 IIIB, AJCC 9th edition) will be enrolled.
Patients will receive 3 cycles of neoadjuvant treatment (every 3 weeks):
Quad Shot radiotherapy (14-14.8 Gy/4 fractions, Day 1-2) Tislelizumab (200 mg, Day 3) Platinum-based doublet chemotherapy (Day 3): Carboplatin (AUC 5) or Cisplatin (75 mg/m²) combined with Pemetrexed (500 mg/m², for non-squamous) or Paclitaxel (175 mg/m², for squamous).
Following 3 cycles of neoadjuvant therapy, patients will undergo surgery 4-6 weeks (±7 days) after the last dose. Postoperative adjuvant therapy will be administered at the investigator's discretion according to NCCN and CSCO guidelines.
Objectives and Endpoints:
The primary objective is to evaluate the antitumor efficacy of this regimen, with the primary endpoint being the pathological complete response (pCR) rate. Secondary endpoints include major pathological response (MPR) rate, R0 resection rate, objective response rate (ORR) per RECIST v1.1, event-free survival (EFS), overall survival (OS), safety (NCI CTCAE v5.0), feasibility, surgical complications (Clavien-Dindo classification), and QS radiotherapy-related toxicities.
Sample Size:
A total of 12 patients will be enrolled, with at least 10 evaluable patients included in the primary endpoint analysis to account for an estimated 2 dropouts.
Study Duration:
The estimated enrollment period is 6-12 months, with an anticipated study completion date of December 2031.
Exclusion Criteria:
Patients receive 3 cycles of neoadjuvant therapy (every 21 days). Each cycle consists of: * Quad Shot radiotherapy (14-14.8 Gy/4 fractions on Day 1-2) * Tislelizumab (200 mg, Day 3) * Platinum-based doublet chemotherapy (Day 3): Carboplatin (AUC 5) or Cisplatin (75 mg/m²), combined with Pemetrexed (500 mg/m² for non-squamous) or Paclitaxel (175 mg/m² for squamous). Surgery is performed 4-6 weeks (±7 days) after the third cycle. Postoperative adjuvant therapy is administered at the investigator's discretion according to NCCN and CSCO guidelines.
Radiation: Quad Shot Radiotherapy · Drug: Tislelizumab · Drug: Carboplatin or cisplatin · Drug: Pemetrexed or Paclitaxel
3.7 Gy per fraction, twice daily (with an interval of at least 6 hours), for 4 fractions over 2 consecutive days (Days 1-2 of each cycle). Total dose of 14.8 Gy per cycle, repeated every 3 weeks for 3 cycles (cumulative dose 44.4 Gy). Delivered using IMRT or VMAT.
200 mg administered via intravenous infusion on Day 3 of each 21-day cycle for 3 cycles.
Carboplatin (AUC 5) or Cisplatin (75 mg/m²) administered intravenously on Day 3 of each 21-day cycle for 3 cycles.
Pemetrexed (500 mg/m²) for non-squamous NSCLC or Paclitaxel (175 mg/m²) for squamous NSCLC, administered intravenously on Day 3 of each 21-day cycle for 3 cycles.
Pathological Complete Response (pCR) Rate
The proportion of patients with no residual viable tumor cells in the resected primary tumor and regional lymph nodes, as assessed by pathological review. Patients who do not undergo surgery will be considered as not achieving pCR.
Time frame: After completion of neoadjuvant therapy and surgery (approximately 4-6 weeks after the last dose of neoadjuvant therapy)
Major Pathological Response (MPR) Rate
The proportion of patients with ≤10% viable tumor cells in the resected specimen.
Time frame: After completion of neoadjuvant therapy and surgery (approximately 4-6 weeks after the last dose of neoadjuvant therapy)
R0 Resection Rate
The proportion of patients achieving microscopically margin-negative resection.
Time frame: At time of surgery
Objective Response Rate (ORR) per RECIST v1.1
The proportion of patients achieving a confirmed complete or partial response according to RECIST v1.1.
Time frame: Up to 14 days before surgery
Event-Free Survival (EFS) and 2-Year EFS Rate
Time from enrollment to disease progression, local recurrence, distant metastasis, or death from any cause.
Time frame: Up to 60 months after enrollment
Overall Survival (OS) and 2-Year OS Rate
Time from enrollment to death from any cause.
Time frame: Up to 60 months after enrollment
Incidence and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-Related Adverse Events (irAEs)
Evaluated according to NCI CTCAE v5.0.
Time frame: From informed consent to 90 days after the last dose of study treatment
Feasibility (Completion Rate of Neoadjuvant Therapy and Surgery)
Proportion of patients completing 3 cycles of neoadjuvant therapy and undergoing surgery as planned; surgical delay rate.
Time frame: Up to 4-6 weeks after the last dose of neoadjuvant therapy
QS Radiotherapy-Related Toxicity
Incidence and severity of radiation pneumonitis, esophagitis, dermatitis, myelosuppression, and myocarditis, graded according to NCI CTCAE v5.0.
Time frame: Up to 90 days after the last dose of radiotherapy
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Carcinoma, Non-Small-Cell Lung→
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology