SCCHN represents the sixth most common malignancy with 650 000 new cases and 350 000 SCCHN-related deaths reported annually worldwide. A majority of patients present with stage III or IV M0 disease, with a 5 year overall survival from 30% to 50%. Results of recent randomized trials evaluating induction chemotherapy by DCF are conflicting, and benefit on overall survival is uncertain. It is needed to improve efficacy of induction chemotherapy without increase toxicities. Tumours can actively evade destruction by the immune system by exploiting inhibitory checkpoint pathways that suppress antitumour T-cell responses. Antibody therapy to block immune checkpoints activated by the programmed cell death ligand-1 (PD-L1) has shown survival benefit in recurrent or metastatic SCCHN. Durvalumab is a selective, high affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Durvalumab has shown encouraging antitumour activity in SCCHN with a manageable safety profile. The aim of this open-label, multi-center, Phase 1-b study is to characterize the safety profile of the combination of DCF with durvalumab.
Patients aged ≥ 18 yr with histologically confirmed SCC of the oral cavity, oropharynx, larynx or hypopharynx, previously untreated, with indication of induction chemotherapy will be eligible. The primary objective is to determine the recommended Phase 2 dose (RP2D). The secondary objectives are to document any antitumor activity (PFS, ORR, RECISTv1.1 criteria), to estimate the pharmacokinetic parameters of durvalumab, to explore the relationships between immune capacity, specificity, activation state and clinical outcome. The study will be conducted in 2 parts: a dose-deescalation part to determine the RP2D (6 pts), and an expansion part (30 pts). The durvalumab will be administered every 3 weeks for 3 injections at week 1, 4, 7. The durvalumab first dose level is 1120 mg and the dose level -1 is 750 mg Q3W. The chemotherapy will be administered every 3 weeks at week 1, 4, 7 at the following doses: Docetaxel 75mg/m2 on D2, Cisplatin 75mg/m2 on D2, 5 Fluorouracil 750mg/m2/day from D2 to D6.
Clinical trial identification
NCT 02997332 Eudract number 2015-004146-25
Legal entity responsible for the study
INCA and ARC Aknowledgement to Astra Zeneca for providing the drug
C. Even: Advisory board: AstraZeneca, Bristol-Myers Squibb, Innate Pharma, Merck Serrono, MSD. C. Le Tourneau: Consulting fees: AstraZeneca. J. Fayette: Honoraria: Bristol-Myers Squibb, AstraZeneca. All other authors have declared no conflicts of interest.