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The ETOP NICOLAS phase II trial

The addition of nivolumab to concurrent first-line chemo-radiotherpy in stage III NSCLC appears to be safe and tolerable, according to the early interim safety analysis of the ETOP NICOAS trial (abstract #8510).


The feasibility of combined chemo-radiotherapy (chemo-RT) and concurrent PD-1 inhibition is of high scientific interest and has shown promising results in pre-clinical models. So far, concurrent immune-checkpoint inhibition and radical thoracic RT has never been assessed in a clinical trial.


NICOLAS is a phase II trial evaluating the safety of the addition of nivolumab to first-line chemo-RT in stage III NSCLC. Efficacy will be evaluated if a safety conclusion has been achieved, based on a hierarchical design. Patients received 3 cycles of platinum-based chemotherapy (etoposide, vinorelbine or pemetrexed) and radical RT of 66 Gy. Nivolumab treatment (240 mg / Q4W) started concurrently to RT. The primary safety endpoint is defined as the rate of pneumonitis grade ≥3 at 6 months post RT. An interim analysis was scheduled when the first 21 patients reached 3 months follow-up after completion of RT, based on the assumption that 70% of the pneumonitis events occur within the first 3 months. An early positive safety conclusion is reached at interim analysis if there is no incidence of pneumonitis grade ≥3 in the initial 21 patients (exact group sequential design at one-sided significance level of 0.05 and power = 83%, testing a 6-month pneumonitis rate ≥33% versus ≤15%).


Up to December 14, 2017, 49 patients have been recruited with a median follow-up of 6.6 months [95% CI: 5.6, 7.8]. The median age is 63 years, with the majority of the patients being male (67.3%), former smokers (75.5%) and with tumor stage IIIb (65.3%). The most frequently observed adverse events (AEs) are fatigue and anemia. No unexpected AEs or increased safety risk were observed. For the first 21 patients, no pneumonitis grade ≥3 was observed by the end of the 3-month post RT follow-up period. The majority of these patients (18 patients) were on a concurrent chemo-RT schedule.


This early interim safety analysis provides evidence that the addition of nivolumab to concurrent chemo-RT is safe and tolerable. In a next step, the 1-year progression-free survival will be evaluated according to the hierarchical design in an expanded patient cohort. Clinical trial information: NCT02434081

Peters S et al. Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-RT regimen in unresectable locally advanced NSCLC: The ETOP NICOLAS phase II trial, abstract #8510
Presented on Sunday, June 3,2018



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