4934 - 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)

Background

Based 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.

Methods

This randomized multicenter phase III trial comprises two cohorts of pts deemed fit (Cohort 1) to receive high dose cisplatin (CDDP 100 mg/m², Q3W) or unfit (Cohort 2) to receive CDDP. The SoC is IMRT (69.96 Gy, 33 fractions) combined with CDDP in Cohort 1 (arm A) and with cetux (arm D) in Cohort 2 (400 mg/m² Day-7 and 250 mg/m² weekly). In both cohorts, experimental (exp) arms are IMRT concomitant with cetux (same schedule as in SoC) and avelumab (10 mg/kg Day-7 and every 2 weeks) followed by avelumab 10 mg/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.

Results

Between 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 55 Gy. 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.

Conclusions

The 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 identification

NCT02999087.

Editorial acknowledgement

Legal entity responsible for the study

GORTEC.

Funding

Merck Serono.

Disclosure

Y. 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.