objectives: chemo-radiotherapy (crt) and concurrent pd-1 inhibition has shown promising results in pre-clinical models. so far, the feasibility of delivering concurrent crt and pd-1/pd-l1 inhibition has never been assessed in a clinical trial.
material and methods: nicolas is a phase-ii trial evaluating the safety and efficacy of nivolumab combined with crt in stage iii nsclc. patients received 3 cycles of platinum-based chemotherapy and concurrent rt (66gy/33fractions). nivolumab started concurrently with rt. the primary endpoint was 6-month post-rt rate of grade-≥3-pneumonitis. a formal interim safety analysis (ia) was scheduled when the first 21 patients reached 3 months follow-up post-rt. an early positive safety conclusion would be reached at ia if there were no grade ≥3-pneumonitis in those patients. efficacy evaluation was planned provided the safety conclusion was reached.
材料与方法：nicolas是一项ii期临床试验，旨在评估nivolumab联合crt治疗iii期nsclc的安全性和有效性。患者接受3个周期的铂类化疗和同步rt (66 gy/分33次完成)。nivolumab与rt同步开始，主要终点为rt 6个月后≥3级肺炎的发生率。前21例完成rt后3个月随访的患者被安排进行一项正式的中期安全分析(ia)。如果这些患者中没有出现≥3级肺炎，则ia可得出早期阳性安全性结论。在得出安全性结论的前提下，进行疗效评价。
results and conclusion: as of 13 december 2018, 82 patients were recruited with median follow-up of 13.4 months. the most frequent adverse events (aes) were anaemia, fatigue and pneumonitis. no unexpected aes or increased toxicities were observed. for the first 21 patients, no grade-≥3-pneumonitis was observed by the end of the 3-month post-rt follow-up period. the early safety ia provides evidence that the addition of nivolumab to concurrent crt is safe and tolerable regarding the 6-month rate of pneumonitis grade ≥3 at the one-sided significance level of 5%. following that, the 1-year progression-free survival will be evaluated in an expanded patient cohort. nicolas trial creates the opportunity for assessing the activity of the combination of checkpoint with concurrent crt in larger prospective trials for locally advanced nsclc.