Neo-adjuvant chemo/immunotherapy for the treatment of resectable stage IIIA non-small cell lung cancer (NSCLC): A phase II multicenter exploratory study” NADIM trial

Abstract

Background: Lung cancer is the primary cause of cancer mortality in western countries. The cure is unlikely in patients with NSCLC and locally advanced stage who are not surgical candidates, with a 3-year survival rate of 27% in those patients receiving chemotherapy and concomitant radiotherapy. On the contrary, in localized stages (stage I, II, IIIA) with surgical resection and cytostatic therapy, a survival of 5 years of 51% is achieved. Currently, there is no consensus on the best standard treatment: the surgical management of stage IIIA NSCLC remains highly controversial and most patients with stage IIIB disease are generally considered inoperable. Since distant metastases remain the major site of failure, it is likely that more effective cytotoxic or other anti-tumor agents will be required. Chemotherapy stimulates an immune response against tumors, which may facilitate immunotherapy anticancer activity. Evidence of synergy between chemotherapy and immunotherapy was shown in several studies. Trial design: Phase II, single-arm, open-label multicenter study that assesses feasibility, safety and efficacy of combined neoadjuvant therapy with Nivolumab 360 mg + Paclitaxel 200mg/m2 +Carboplatin AUC 6 Q3W, three cycles, in resectable stage IIIA NSCLC patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg Q2W for 4 months and Nivolumab 480mg Q4Wfor 8 months. The primary endpoint will be Progression Free Survival at 24 months from diagnosis and to assess the efficacy of the combination. The secondary endpoints will be time to progression and overall survival at 3 years, response rate, toxicity profile of the combination, the down-staging rate and complete resection rate. Also, surgical outcome and complications will be assessed. Perform correlatives studies with the objectives of exploring the expression of other biomarkers, such as PD-L1, in tumor tissue, free DNA and circulating tumor cells in liquid biopsy. Describe whether PD-L1 expression is a predictive biomarker for ORR, describe PFS in PD-L1+(≥1%) population and report imaging response versus pathological response rate.