1118PD - Avelumab-cetuximab-radiotherapy versus standards of care (SoC) in patients (pts) with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Safety phase of randomized trial GORTEC 2017-01 (REACH)

Abstract

BackgroundBased on the hypothesis of a synergistic effect of the anti-PDL1 avelumab when combined with cetuximab (cetux) and RT, this new combination is tested in a large scale randomized trial against two well established SoC in LA-SCCHN pts. MethodsThis randomized multicenter phase III trial comprises two cohorts of pts deemed fit (Cohort 1) to receive high dose cisplatin (CDDP 100mg/m², Q3W) or unfit (Cohort 2) to receive CDDP. The SoC is IMRT (69.96Gy, 33 fractions) combined with CDDP in Cohort 1 (arm A) and with cetux (arm D) in Cohort 2 (400mg/m² Day-7 and 250mg/m² weekly). In both cohorts, experimental (exp) arms are IMRT concomitant with cetux (same schedule as in SoC) and avelumab (10mg/kg Day-7 and every 2 weeks) followed by avelumab 10mg/kg bi-monthly for 12 months (arms B and C). The primary objective is to test whether exp arm is superior to SoC for progression-free survival in each cohort, with 400 and 268 pts to be randomized to Cohort 1 and 2 respectively. Monitoring of grade ≥4 acute adverse events (AE) in both exp arms was planned with null and alternative hypotheses of 15% and 35%, 1-sided α error = 0.10, Lan-DeMets α spending function, power 95%. This safety phase was approved by the Independent Data and Safety Monitoring Committee (IDSMC) and planned to be run on the first 41 pts randomized in exp arms, in 3 steps, after 8 weeks follow-up of 14, 27 and 41 pts. ResultsBetween September 2017 and August 2018, 82 pts with LA-SCCHN were randomized including 41 in the exp arms. All pts of exp arms received the entire RT, except one in arm C with early stop after 55Gy. In exp arms, 36 pts (88%) and 31 pts (76%) received the expected number of avelumab and cetux administrations during RT. In the exp arms, the most common grade ≥3 AE were radiation dermatitis, mucositis and dysphagia. Grade ≥4 AEs occurred in 5/41 (12%) pts in the exp arms (all in arm C), in 3/21 (14%) pts in arm A and 2/20 (10%) in arm D. Only one grade 5 AE occurred in arm A. ConclusionsThe combination of avelumab, cetuximab and RT is tolerable for pts with LA-SCCHN in the safety phase of this ongoing phase 3 trial and an approval to continue the trial was given by IDSMC. Clinical trial identificationNCT02999087. Legal entity responsible for the studyGORTEC. FundingMerck Serono. DisclosureY. Tao: Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Research grant / Funding (institution): Debiopharma; Research grant / Funding (institution): Pfizer. J. Thariat: Advisory / Consultancy: BMS; Advisory / Consultancy: Nanobiotix. J. Guigay: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Innate pharma; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono. J. Bourhis: Advisory / Consultancy: Merck Serono; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD. All other authors have declared no conflicts of interest.