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Found 1 Presentation For Request "970P"
970P - MEDINDUCTION: Phase I trial evaluating the safety of durvalumab in combination with docetaxel, cisplatin and 5-FU (DCF) as induction therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN)
- Caroline Even (Villejuif, France)
Abstract
Background
The majority of patients (pts) with SCCHN present with stage III or IV locally advanced disease. The benefit of induction chemotherapy on overall survival (OS) remains uncertain. Improving efficacy without increasing toxicity is warranted. Monoclonal antibodies (mAb) targeting immune checkpoints, such as programmed cell death ligand-1 (PD-L 1), have been shown to improve OS in recurrent or metastatic SCCHN pts. Durvalumab is an IgG1 mAb that blocks PD-L1 binding to PD-1. The aim of this multi-centre, phase Ib study was to characterize the safety profile of durvalumab in combination with DCF.
Methods
Pts aged ≥ 18 yr with untreated SCCHN were eligible. The primary objective was to determine the recommended phase II dose (RP2D). The study was conducted in 2 parts: a dose-deescalation part to determine the RP2D (6 pts), and an expansion part (30 pts). Durvalumab was administered every 3 weeks (q3w) for 3 cycles (cy). The first dose level was 1120 mg. Chemotherapy was administered q3w at the following doses: D 75mg/m2 on D2, C 75mg/m2 on D2, F 750mg/m2/D from D2 to D6.
Results
14 pts were treated, 6 in the de-escalation part and 8 in the expansion part. Median age was 61 yr [50-71], 93% male. Cancer primary site was oropharynx 36%, oral cavity 36%, hypopharynx 21%, larynx 7%. 29% were stage III, 64% IVa, 7% IVb. Only 9 pts completed the 3 cy of induction; 3 stopped after 1 cy due to toxicity and 2 after 2 cy after investigator’s decision. Six pts experienced dose limiting toxicities (3 grade 3 colitis, 1 grade 4 duodenal perforation, 1 grade 4 mucositis, 1 grade 4 febrile neutropenia with grade 4 sepsis). 11 pts (79%) experienced grade 3/4 adverse events but no grade 5. Median follow-up was 8.08 months. One-year OS rate was 60%, and one-year progression free survival rate was 63.8%. Of the 9 pts who completed the 3 cy of induction, none presented progressive disease, 3 had a complete response and 6 had a partial response.
Conclusions
Despite a promising activity of the combination of DCF with durvalumab in terms of response rate, the trial stopped early due to toxicity.
Clinical trial identification
NCT02997332.
Legal entity responsible for the study
Gustave Roussy, Cancer Campus, Grand Paris.
Funding
AstraZeneca.
Disclosure
C. Even: Advisory/Consultancy: BMS; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck Serono. C. Le Tourneau: Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Rakuten; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: GSK. A. Marabelle: Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Research grant/Funding (institution), Travel/Accommodation/Expenses: disclosure information - over the last 5 years (2014-2019) Aurélien Marabelle institutional links: Principal Investigator of Clinical Trials from the following companies: Roche/Genentech, BMS, MSD, Pfizer, Lytix pharma, Eisai, AstraZeneca/MedImmune, Tesa. J. Fayette: Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche; Advisory/Consultancy: Servier; Advisory/Consultancy: Merck Serono. All other authors have declared no conflicts of interest.