A Phase III Clinical Trial of Adjuvant Treatment With Sacituzumab and Zimberelimab for Stage IB-IIIA-IIIB(N2) Previously Resected (R0) Non-small Cell Lung Cancer Patients That Did Not Achieve Pathological Complete Response After Neoadjuvant treatment_ARIAN
Open-label, phase III, randomized, stratified (PDL1- vs PDL1+), 3 arms, multicenter clinical trial. 129 resected patients (43 per arm) with stage from IB to IIIA and IIIB (N2) non-small cell lung cancer that do not achieve pathologic complete response (pCR) after neoadjuvant treatment. This clinical trial has 3 arms of treatment. ARM 1: Observation 10 months, ARM 2: treatment with immunotherapy (Zimberelimab) for 13 cycles and ARM 3: treatment with Sacituzumab Govitecan and Zimberelimab for 8 cycles and Zimberelimab monotherapy for 5 cycles. The primary objective is to evaluate the disease-free survival (DFS): defined as the length of time from randomization to the earliest event defined as disease recurrence, any new lung cancer (even in the opposite lung), or death from any cause at any known point in time. Patient accrual is expected to be completed within 2 years, treatment is planned to extend during 1 years and the patients will be followed up for 2 years. The study will end once survival follow-up has concluded.
• 1\. Patients diagnosed of primary non-small cell lung cancer, histologically confirmed.
• 2\. Patients should be classified postoperatively in stage IB, IIA, IIB, IIIA or IIIB (N2) according to pathological criteria (pTNM) and according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
• 3\. Complete surgical resection (R0) of the primary NSCLC is also essential. Surgeons are strongly advised to dissect or obtain samples of all accessible lymph node levels, as established in the European Society of Thoracic Surgeons guide. Consequently, at the end of the surgical intervention it is recommended to have obtained samples of a minimum of 3 specific mediastinal ganglionic lobe stations (N2), one of which should include station 7, and at least one N1 station
• 4\. The surgical intervention may consist of a lobectomy, sleeve resection, bilobectomy or pneumonectomy, as determined by the responsible surgeon based on intraoperative findings. Patients who have had only segmentectomies or wedge resections are not considered eligible for participation in this study except if R0 resection can be confirmed.
• 5\. Only patients that do not achieve pathological complete response (pCR) seen in the surgical piece after neoadjuvant therapy are eligible.
• 6\. Preoperative (neoadjuvant) use of platinum-based chemotherapy + immunotherapy (anti PD-1) is mandatory.
• 7\. Preoperative, postoperative, or scheduled radiation therapy is not accepted for a later time. Patients with only N2 disease, who have to receive post-operative adjuvant radiotherapy will not be eligible.
• 8\. A minimum of 3 weeks must have elapsed between the surgical intervention performed for the NSCLC and the randomization. Adjuvant treatment must start between the 3rd and the 10th week from surgery.
• 9\. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• 10\. Patients aged ≥ 18 years.
• 11\. PDL1 value analysed locally (hospital must be able to provide this value before randomization)
• 12\. PET-CT and brain CT before randomization to confirm the absence of distant disease.
• 13\. Adequate hematologic and organ function
• 14.All patients are notified of the investigational nature of this study and signed a written in-formed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
• 15.For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception
• 16\. For male patients with female partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception
• 17\. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drugs.
• 18.Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.
• 19.Patient capable of proper therapeutic compliance and accessible for correct follow-up
• 20\. Patients with a life expectancy of at least more than 12 weeks