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.
properly treated non-melanotic skin cancer
cancer in situ treated with curative intent or other malignancies treated with curative intent and without signs of disease for a period of> 3 years after the end of the treatment and which, in the opinion of the doctor in charge of their treatment, do not present a substantial risk of relapse of the previous malignant disease.
2.T4 patients with invasion of heart, great vessels, carina, trachea, oesophagus or spine
3. Patients with ALK translocation, STK11 o KEAP1 known mutations before inclusion in this trial.
Parallel
Zimberelimab
DrugZimberelimab is a fully human IgG4 monoclonal antibody targeting human PD-1. PD-1 is a type I transmembrane protein that is part of the immunoglobulin gene superfamily and the CD28 family of cell surface receptors. PD-1 is an inhibitory immune checkpoint protein that is expressed on activated B cells, T cells, and myeloid cells, and it plays a key role in limiting the activity of effector T cells. Zimberelimab is formulated at 30 mg/mL in a buffer solution containing histidine/histidine-HCl buffer solution, sucrose, sodium chloride, and polysorbate 80, at pH 5.5. The investigational product is supplied as a vial contains 120 mg of active Zimberelimab at a concentration of 30mg/mL. No premedication nor profilaxis is needed before Zimberelimab administration. Zimberelimab doses are administered by IV infusion over 60 minutes, followed by a 30- to 60-minute observation period, on D1 of each 21-day cycle.
Sacituzumab govitecan
DrugSacituzumab govitecan (SG) is an ADC composed of the following 3 components: o The humanized monoclonal antibody hRS7 IgG1κ, which binds to Trop-2, a transmembrane calcium signal transducer that is overexpressed in many epithelial cancers. o The camptothecin-derived agent SN-38, a topoisomerase I inhibitor. o A hydrolyzable linker, with the company designation as CL2A that links the humanized monoclonal antibody to SN-38. Sacituzumab govitecan is approved globally for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) and HR+ breast cancer.
Cisplatin
DrugCisplatin-based adjuvant chemotherapy Cisplatin - CAS 15663-27-1, is a platinum coordination complex with potent anti-neoplastic activity. Induces apoptosis in cancer cells, possibly via caspase-3 activation.
Carboplatin
DrugCisplatin-based adjuvant chemotherapy Structure: The cis-diamino (cyclobutane-1, 1 dicarboxylate) plating. Stability: 24 hours at ambient temperature in 5% glucose, glucosamine or physiologic saline. It is recommended not to dilute with chlorinated solutions for this could affect the carboplatin. Route of administration: Intravenous infusion. Guidelines of Carboplatin administration: According to the standard of each center. Other Name: ATC code: L01XA02
Disease free survival
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.
Overall survival
defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.
Change in levels of ctDNA during treatment
Analyze plasma samples and quantifying the amount of circulating tumor DNA (ctDNA) by NGS.
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