D-BACE in Combination With Chemotherapy and Carelizumab for Resectable II-IIIA or Potentially Resectable T3-4N2 Stage IIIB NSCLC

This study was a single-arm prospective single-center phase II study. Seventy patients with untreated resectable II-IIIA or potentially resectable T3-4N2 IIIB NSCLC will be included in this prospective study. The aim of this study is to evaluate the clinical efficacy and safety of D-BACE combined with neoadjuvant chemotherapy and camrelizumab in patients with resectable stage II-IIIA or potentially resectable T3-4N2 IIIB NSCLC. The treatment regimen was three cycles of D-BACE (epirubicin 50mg loaded on DCB microspheres) combined with chemotherapy and camrelizumab (the specific chemotherapy regimen was determined by the investigator, and generally platinum-based doubuse chemotherapy was used). Adverse events will be monitored throughout the trial and their severity will be graded according to the NCI CTCAE, version 5.0. At the same time, tissue and blood samples were dynamically collected during the treatment for related translational research exploration. Patients could discontinue the regimen if: Having comorbidities that significantly affect the assessment of clinical status or require discontinuation of protocol treatment (investigator's discretion); Unacceptable treatment toxicity; Disease recurrence or new primary invasive malignancy; At patient's request 4.1 Screening Subjects will complete whole-body PET-CT and contrast-enhanced brain MR Before enrollment to determine stage II-IIIB NSCLC. Patients were required to obtain adequate tissue or cell pathological diagnosis, relevant immunohistochemistry, PD-L1 protein immunohistochemistry and NGS testing before enrollment. At the same time, peripheral blood samples were collected before treatment for related indicators. Tumor tissue was provided in newly obtained formalin-fixed specimens, preferably, or in old formalin-fixed paraffin-embedded specimens from sites not irradiated prior to biopsy. Tumor tissue must be archived (tissue blocks) before treatment. Slides ≤6 months old or recently fresh tumor biopsy slides submitted to the local study center),PD-L1 status determined: PD-L1 positivity was defined as 1% tumor cell membrane staining positive in at least 100 evaluable tumor cells. PD-L1 negative: defined as \< 1% positive tumor cell membrane staining in at least 100 evaluable tumor cells PD-L1 nonevaluable/ambiguous: defined as subjects with insufficient sample quantity or quality to determine PD-L1 status by staining, or subjects with adequate tissue sample but still unable to determine PD-L1 status were classified together with PD-L1-negative subjects. Screening (baseline) assessments were to be performed within 28 days before the first D-BACE. 4.2 Neoadjuvant therapy: D-BACE should be administered within 28 days of baseline screening by: One vial of 300-500μm DC Bead was loaded with 50mg epirubicin, and after full drug loading, 10-20ml of non-ionic contrast agent was added. Under the monitoring of digital subtraction angiography (DSA) equipment, femoral artery puncture was performed according to the technical specification of Seldinger puncture. Cobra, MIK, and single curved angiography catheters were used to explore the opening of tumor feeding arteries and perform angiography to understand the distribution of feeding arteries and tumor vessels. If systemic artery-pulmonary artery/pulmonary vein shunt is found during angiography, embolic materials such as blank microspheres, PVA or microcoils can be used to block the shunt. When the spinal artery was determined to be avoided, drug-loaded microspheres were injected into the tumor feeding artery through a microcatheter for chemoembolization. The injection rate was 1 mL/ min. The forward blood flow of the target embolized vessel must be maintained. "If" near blood stasis "is observed during the injection (i.e., the columnar contrast material in the vessel disappears after 2-5 heartbeats), the injection must be stopped to avoid backflow of the embolic agent, regardless of the actual amount of microspheres injected." In contrast, if "near blood stasis" did not occur after the target dose was fully infused, no additional bolusing of embolic agents was administered. After the operation, the arterial catheter and sheath were removed, the arterial puncture point was compressed and bandaged, and the hip joint was immobilized for more than 6 hours. Neoadjuvant chemotherapy and camrelizumab should be administered within 7 days after D-BACE. The chemotherapy regimen was determined by the investigator. The chemotherapy regimen was generally platinum-based doubuse chemotherapy, such as pemetrexed (500mg/m2) plus carboplatin (AUC=5) (non-squamous carcinoma). Albumin paclitaxel (260mg/m2) combined with carboplatin (AUC=5). 4.3 Local treatment (surgery, SBRT, ablation, particle or D-BACE treatment) : PET-CT and contrast-enhanced MRI were performed after 3 cycles of D-BACE combined with chemotherapy and camrelizumab. The subsequent treatment strategy was evaluated by a multidisciplinary team. If surgical resection was considered, the specific surgical plan was determined by the surgeon. Accepted type of resection (negative margin), including lobectomy, sleeve lobectomy, bilateral lobectomy, or pneumonectomy; If the lesion could not be completely removed or the patient could not tolerate surgery after treatment, the radiotherapy department and interventional department would evaluate the treatment options such as local radiotherapy or ablation, seed, and D-BACE. 4.4 Adjuvant therapy after local treatment: For this study, adjuvant therapy after local treatment was determined by the investigator. The main regimens included standard 3-4 cycles of adjuvant chemotherapy or immunomaintenance therapy. EGFR mutations were deleted 4.5 Follow-up Each subject will be monitored for adverse events for at least 30 days after the end of treatment (serious adverse events will be collected for a maximum of 90 days after the end of treatment). Tumor assessments must continue according to the protocol and the subject will undergo post-treatment follow-up for disease status until one of the following events occurs :(1) disease progression; (2) initiation of non-investigational cancer treatment; (3) withdrawal of consent; (4) loss of follow-up or (5) death. Evaluation was performed by means of computed tomography (CT) of the chest and total abdomen (with enhanced venography, including the liver and adrenal glands and sites of suspected/known disease). Imaging evaluation was performed before each interventional embolization procedure. Postoperative baseline imaging was performed 3 months after local treatment and then every 12 weeks (±7 days) for up to 2 years, with primary chest (contrast-enhanced) CT. It is recommended to perform head MR At least once a year. If there are obvious neurological symptoms, head MR Should be performed in time. 4.6 Postoperative Radiotherapy Postoperative radiotherapy (PORT) will be administered at the discretion of the treating oncologist according to standard of care. Based on the current international and domestic phase III randomized controlled trials of postoperative radiotherapy, postoperative adjuvant radiotherapy is not routinely performed for patients with complete resection, and for patients with non-R0 resection, postoperative adjuvant radiotherapy is not recommended. 4.7 Definition of end of study The start of the trial was defined as the first visit of the first subject. After 3 cycles of D-BACE combined with chemotherapy and camrelizumab, local intervention was performed within 6 weeks after assessment by imaging PET-CT and brain MRI enhancement scan, and subsequent adjuvant therapy was determined by the investigator. EGFR mutations were deleted. Survival follow-up continued for 5 years. The study was closed once survival follow-up was completed.