Definitive cisplatin-based chemoradiotherapy (CRT) in patients (pts) with locoregionally advanced head and neck SCC is associated with acute and long-term toxicities. Immune checkpoint inhibitors, such as anti-PD1/L1 and anti-CTLA4 antibodies, are actively being investigated in this disease setting. HN.9 evaluates a chemo-sparing approach in pts with HPV+ intermediate risk LA-OSCC (defined by AJCC 8th edition as: T1-2N1 smokers; T3N0-N1 smokers and T1-3N2 any smoking history).
CCTG HN.9 is a non-comparative, randomized phase II study in intermediate risk HPV+ LA-OSCC. Pts will be randomized at a 1:1:1 ratio to: CRT (arm A); immunoradiotherapy (IRT) with durvalumab (durva) followed by durva maintenance (Arm B); IRT followed by durva and tremelimumab (treme) maintenance (Arm C). Treatment schedule: 70 Gy/35 over 7 weeks (RT) + cisplatin 100mg/m2 d1, 22, 43 (Arm A); RT + durva 1500 mg d-7, 22 (IRT) followed by Q4W for 6 doses (Arm B); IRT followed by durva Q4W for 6 doses + treme Q4W for 4 doses (Arm C). Key eligibility criteria: intermediate risk HPV+ LA-OSCC; adequate organ function; no autoimmune disorders; no immunosuppressive therapy. Pts will be stratified by smoking status, age, ECOG PS and TNM classification. The primary objective is to estimate the efficacy of the 3 treatment arms in terms of event-free survival (EFS). Secondary objectives: overall survival; loco-regional control; distant metastasis-free survival; quality of life and swallowing assessments; economic evaluation. Correlative studies include: immunophenotyping, radiomic, ctDNA, microbiome analyses. The planned sample size is 240 pts over 2.5 years with 3 years follow-up. Assuming the new treatment will improve 3-years EFS from 83 to 91%, with one-sided type I error of 0.1, 80 pts/arm, the study will have 80% of power to reject the null hypothesis (3-year EFS rate is 83% or lower). Study activation: April 2018.
Clinical trial identification
Legal entity responsible for the study
Canadian Cancer Trial Group.
Supported by AstraZeneca.
A. Spreafico: Advisory Board: Novartis, BMS, Merck; Research support (to institution): AstraZeneca/MedImmune. K. Sultanem, S.V. Bratman, J. Hilton, J.N. Waldron: Research support (to institution): AstraZeneca/MedImmune. J-P. Machiels: Advisory board member: MSD (uncompensated), Debio, Nanobiotix, Innate. S. Oosting: Research grants (to institution): Novartis, Pfizer, Celldex. L.L. Siu: Consultant: AstraZeneca/MedImmune; Research support (to UHN): AstraZeneca/MedImmune. W.R. Parulekar: Advisory board fees: Pfizer. All other authors have declared no conflicts of interest.