Phase 3 study of durvalumab (MEDI4736) alone or in combination with tremelimumab versus standard of care (SoC) in platinum-resistant recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): EAGLE

Background

SCCHN tumours evade immune detection by exploiting inhibitory immune checkpoints such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Durvalumab is a selective human IgG1 mAb that blocks binding of programmed cell death ligand-1 (PD-L1) to PD-1 (IC₅₀ 0.1 nM) and CD80 (IC₅₀ 0.04 nM), and tremelimumab is a selective human IgG2 mAb inhibitor of CTLA-4. Dual targeting of the non-redundant PD-1 and CTLA-4 pathways induces synergistic antitumour effects according to preclinical data, and was shown to be active and tolerable in a Phase 1b study in patients with NSCLC (NCT02000947). Durvalumab monotherapy has also shown preliminary antitumour activity in a Phase 1/2 study in patients with solid tumours, including a SCCHN cohort (NCT01693562). The Phase 3 EAGLE study (NCT02369874) will compare the efficacy and safety of durvalumab as monotherapy or in combination with tremelimumab to SoC.

Trial design

In this Phase 3, open-label, multicentre, global study, 720 patients with PD-L1⁺ and PD-L1⁻ R/M SCCHN will be randomised (1:1:1) to receive durvalumab (10 mg/kg IV for up to 12 months); tremelimumab (1 mg/kg IV) plus durvalumab (20 mg/kg IV for up to 12 months); or SoC (cetuximab, taxane, methotrexate, or fluoropyrimidine). Stratification factors include PD-L1 status, human papillomavirus status and smoking history. Eligible patients have progressed with a platinum-containing regimen for R/M disease or within 6 months of multimodality therapy containing platinum. Co-primary endpoints are progression-free survival (RECIST v1.1) based on independent central review and overall survival. Secondary outcomes will assess objective response rate, disease control rate, duration of response, and proportion of patients alive and progression free at 6 and 12 months (using RECIST v1.1 and immune-related RECIST); safety (CTCAE v4.03) and tolerability; and health-related quality of life. Exploratory outcomes include pharmacokinetics, immunogenicity, and potential biomarkers of response to treatment. Recruitment is ongoing.

Clinical trial identification

NCT02369874

Disclosure

L. Licitra: consultancy: EISAI, BMS, MSD, Merck-Serono, BI, DEBIOPHARM, SOBI, Novartis, AstraZeneca, Bayer, Roche; Research funds: EISAI, MSD, Merck-Serono, BI, Novartis, AstraZeneca, Roche; travel costs for medical meetings: Merck-Serono, DEBIOPHARM, SOBI, Bayer. R. Haddad: research funding: BMS, Merck, AstraZeneca, VentiRx, Boehringer Ingelheim, Celgene, Bayer; consultant: Merck, Eisai. Bayer, BI NCCN: member: Head and Neck Committee NCCN; Chair: Thyroid Committee. M. Tahara: honoraria from Merck Serono Bristol-Myers Squibb Eisai Otsuka Bayer; research funding from Eisai Merck Sharp & Dohme Boehringer Ingelheim AstraZeneca. T. Goswami: AstraZeneca employee and holds stock options. A. Franks: employee of AstraZeneca. U. Emeribe, A. Jarkowski III: employee of AstraZeneca and has stock ownership. G. Melillo: employee of AstraZeneca and owns stock/stock options in AstraZeneca. R.L. Ferris: Advisory boards: AZ/Medimmune, Bristol Myers Squibb, Celgene, and Merck; research funding: Bristol Myers Squibb, AZ/Medimmune. All other authors have declared no conflicts of interest.