1457PDEfficacy evaluation of concurrent nivolumab addition to a first-line, concurrent chemo-radiotherapy regimen in unresectable locally advanced NSCLC: Results from the European Thoracic Oncology Platform (ETOP 6-14) NICOLAS phase II trial

Abstract Background NICOLAS is a single-arm phase II trial in stage III NSCLC. The safety analysis has earlier provided evidence that nivolumab administration concurrently to chemo-radiotherapy (CRT) is safe and tolerable, with respect to the occurrence of clinically relevant (grade > =3) pneumonitis. According to a hierarchical design, efficacy evaluation was planned provided the safety conclusion regarding pneumonitis was reached. Methods Primary efficacy endpoint is the 1-year (1y) progression-free survival (PFS) rate. Patients (pts) received 3 cycles of platinum-based chemotherapy and concurrent RT (66Gy/33fractions). Nivolumab started concurrently with CRT (360mg, Q3W) and subsequently continued as monotherapy consolidation (480mg, Q4W). The aim was a 1y PFS rate improvement of at least 15%, from 45% to 60%. A sample size of 74 evaluable pts provides power 83%, for testing this efficacy hypothesis, using an exact binomial test at 1-sided alpha 5%. Results PFS is evaluated in 79 pts assigned to concurrent treatment. Two pts died before starting treatment. Up to 20 March 2019, the median follow-up is 16.4 months (m) (Interquartile Range: 11-20 m). The majority of pts are male (67%), former smokers (68%), of median age 62 years. The ECOG performance status at enrolment, is PS 0/1 for 48%/52% of pts, while 64% present with stage IIIb. The Kaplan-Meier estimate of the 1y PFS rate is 54% (95% CI: 41-65%), with median PFS 12.4 m (95% CI: 9, Not estimable). Currently, 62 pts have either been followed beyond 1y or had a PFS event up to that timepoint. The 1y overall survival (OS) rate is 79% (95% CI: 68-87%) while median OS is not reached yet. The most frequent adverse events (AEs) were anaemia, fatigue and pneumonitis. No unexpected AEs or increased toxicities were observed. Conclusions The 1y-PFS estimate will be final when all pts have reached 1y after enrolment, in August 2019. A promising result on the PFS rate, coupled with the already reported evidence that the addition of nivolumab to CRT is safe and tolerable, would further support concurrent immunotherapy and CRT in locally advanced NSCLC. Clinical trial identification NCT02434081. Legal entity responsible for the study European Thoracic Oncology Platform (ETOP). Funding Bristol-Myers Squibb. Disclosure S. Peters: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Biocartis; Honoraria (self): Boehringer Ingelheim; Honoraria (se