Nivolumab with chemotherapy in pleural mesothelioma after surgery: The NICITA trial.
Authors: Shah Rajiv , Klotz Laura V. , Christoph Daniel Christian , Schulmann Karsten , Kopp Hans-Georg , Reinmuth Niels , Ried Michael , de Wit Maike , Buchmeier Eva Lotte , Wesseler Claas , Reck Martin , Bethge Andre , Waller Cornelius , Hoffknecht Petra , Hackanson Bjoern , Schneider Marc A. , Behnisch Rouven , Christopoulos Petros , Eichhorn Martin E. , Thomas Michael 
Published: June 2023

TPS8601 Background: Pleural mesothelioma (PM) is a highly aggressive cancer of the pleura, predominantly caused by prior asbestos exposure. Currently, there is no approved standard therapy for the treatment of early-stage PM. In most cases a multimodal therapy is recommended consisting of locoregional treatment by surgical cytoreduction via extended pleurectomy/decortication (eP/D), which, if feasible, can be combined with hyperthermic intrathoracic chemoperfusion (HITOC), together with inductive or adjuvant chemotherapy. Considering the immunogenic effects of chemotherapy on the tumor microenvironment, synergistic effects are expected when such a treatment is combined with immune checkpoint inhibitor therapy. In addition, interactions between immune infiltrates and mesothelioma cells play a role in the advent of PM, also implying a beneficial role for immunotherapy in this entity. This is also supported by recent clinical data that demonstrated beneficial effects of immune checkpoint inhibitors in patients with advanced PM. The NICITA trial is an investigator-initiated trial, investigating the combination of adjuvant chemotherapy with immune checkpoint inhibitor compared to chemotherapy alone in radically resected patients with early stage PM. Methods: The NICITA trial is a randomized, open-label, phase II clinical trial that is conducted in 14 centers across Germany. Eligible patients have been diagnosed with PM in tumor stages I-III (UICC 8th edition) and epithelioid subtype, and must have undergone cytoreductive surgery by eP/D with or without HITOC. Patients will be randomized 1:1 to receive either a combination of 4 cycles of pemetrexed/platinum-based adjuvant chemotherapy and nivolumab (480 mg q4w) followed by nivolumab maintenance therapy (12 cycles, 480 mg q4w) or 4 cycles of adjuvant chemotherapy only. Stratification will take place according to previous HITOC treatment (yes vs. no), ECOG status (0,1 vs. 2), and achievement of macroscopic complete resection (yes vs. no). The primary endpoint of this trial is time-to-next-treatment. Secondary endpoints include additional measures of efficacy (progression-free survival, overall survival, measures of treatment-beyond-progression) and quality of life, as well as the assessment of safety. Furthermore, a comprehensive longitudinal collection of biomarker samples, including tumor tissue, blood, and stool samples, for an accompanying translational research project is implemented in this clinical trial. Sample size justification: the recruitment of 46 patients to each arm with a low drop-out rate of 13% appears feasible resulting in 40 patients to be analyzed per arm. This sample size will permit a descriptive comparison and adequately describe the tested treatment options as deduced from the precision of the median TNT confidence interval estimate. As of February 2nd 2023, 85 of planned 92 patients have been enrolled into the NICITA trial. Clinical trial information: NCT04177953 .