This randomized phase II trial is to explore the clinical efficacy, safety and feasibility of neoadjuvant immunotherapy plus radiotherapy compared with neoadjuvant immunotherapy plus chemotherapy in operable stage II-IIIA (N+) non small cell lung cancer (NSCLC) and the optimal radiotherapy pattern.
In recent years, the survival rate after diagnosis of non small cell lung cancer (NSCLC) has improved with advances in treatment. In terms of 5-year average overall survival (OS) by stage at the time of diagnosis, OS decreases significantly from stage IB to IIIA NSCLC, with 68% for stage IB, 53-60% for stage II, and 36% for stage IIIA. How to optimize the perioperative treatment strategy to reduce postoperative recurrence and prolong the survival of patients has raised great concern in early and mid-stage NSCLC. Radiotherapy combined with immunotherapy is suggested for advanced NSCLC in preclinical basic studies and recent clinical trials. Stereotactic body radiation therapy (SBRT) at 8 Gy × 3 Fx plays an effective immunoregulated role and can further enhance the antitumor immune response promoted by immune checkpoint inhibitors (ICIs). Although little is known about the optimal SBRT dose and fraction pattern, 6 Gy × 5 Fx or 8-9 Gy × 3 Fx have shown effectiveness in clinical studies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
124
primary tumor SBRT, DT: 24Gy/3Fx, d1-3; positive lymph nodes LDRT, DT: 3Gy/3Fx, d1-3, d22-24 (2 cycles)
toripalimab 240mg ivgtt d4, d24 (2 cycles)
Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum
Shanghai Chest Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGPathlogical complete remission (pCR) rate
Pathlogical complete remission rate
Time frame: 1 year
major pathologic response (MPR) of primary tumor
proportion of residual tumor ≤10%
Time frame: 1 year
Perioperative complications
complications occurring during operation
Time frame: 1 year
Completion of surgery
whether the surgery is completed
Time frame: intraoperative
Rate of R0 resection
rate of participants with tumor margin negative
Time frame: 1 year
treatment emergent adverse event (TEAE)
number of participants who have adverse events occurring during the treatment period
Time frame: 1 year
Event-free survival (EFS)
Event-free survival
Time frame: 3 years
Overall survival (OS)
Overall survival
Time frame: 3 years
circulating tumor DNA (ctDNA)
the expression of circulating tumor DNA
Time frame: 1 year
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toripalimab 240mg ivgtt d1, d22 (2 cycles)
Immune subtypes
the tumor immune microenvironment subtype according to PD-L1 and tumor-infiltrating lymphocytes
Time frame: 1 year
PD-L1 expression
the status of PD-L1
Time frame: 1 year
Tumor mutation burden (TMB)
frequency of tumor gene mutation
Time frame: 1 year