Interim analysis for window of opportunity trial of single dose preoperative durvalumab (D) with or without tremelimumab (T) for operable head and neck squamous cell carcinoma (HNSCC).
Authors: Kim Hye Ryun , Kim Chang Gon , Hong Min Hee , Kim Da Hee , Lim Sun Min , AHN Beung-Chul , Kim Se Hun , Park Young Min , Park Heejung , Cho Byoung Chul , Koh Yoon Woo 
Published: June 2021

e18043

Background: We aim to evaluate the efficacy and safety for single dose of preoperative D with or without T in patients with operable HNSCC with immune correlates. Methods: Patients with histologically confirmed, potentially resectable, stage II, III, and IVA HNSCC were eligible. Enrolled patients were randomized into D or D+T, stratified by primary site and human papilloma (HPV) infection status assessed by p16 expression. A single dose of preoperative D (1500mg) or D+T (1500mg+75mg) was administered and followed 2 to 8 weeks later by surgical tumor resection with curative intent. Postoperative (chemo) radiation (PO-CRT) was planned based on standard guidelines, followed by maintenance with D every 4 weeks for one year. Pathology response was quantified as the proportion of the resection bed with viable tumor, tumor necrosis, fibrosis, and inflammation. The primary objective was to determine the local recurrence rate. Secondary endpoints included pathologic response, safety and tolerability, disease-free survival, and immune dynamics incorporating multiple immunofluorescence and single cell transcriptomic analysis. A total 48 patients are planned to be enrolled. Results: As of Jan. 31, 2021, a total 36 patients were enrolled and received surgical resections with available data for pathologic response (D: 16 patients, D+T: 20 patients). Patient characteristics of both arms were well-balanced: hypopharynx/larynx/oral cavity as primary site (12.5%/12.5%/18.8%/56.3% in D, 20.0%/10.0%/10.0%/60.0% in D+T); HPV positivity (50.0% in D, 50.0% in D+T); cT1/T2/T3/T4 (6.3%/37.5%/31.3%/25.0% in D, 10.0%/25.0%/40.0%/25.0% in D+T); cN0/N1/N2/N3 (25.0%/18.8%/50.0%/6.3% in D, 30.0%/30.0%/40.0%/0% in D+T). Significant tumor shrinkage defined as more than 30% of size reduction was observed in 43.7% (7/16), including 2 patients with complete response in D and 20.0% (4/20) in D+T. During 128 days of median follow-ups, local recurrence was observed in 2 patients of D+T arm (5.6%). HPV positivity was numerically associated with favorable treatment response (average tumor shrinkage; -21.8% in p16-positive vs. -6.4% in p16-negative). Meaningful pathologic response was achieved in terms of tumor necrosis (average 10.3% in D, 5.5% in D+T), fibrosis (average 13.4% in D, 10.3% in D+T), and inflammation (average 15.0% in D, 5.8% in D+T), without significant differences according to HPV positivity. After preoperative D or D+T, serious adverse events and unexpected surgical complications did not occur. Conclusions: These early data suggested that preoperative D or D+T in patients with operable HNSCC was safe and feasible and had the potential to provide clinical benefits. The trial is ongoing and the updated outcomes with immune correlates including immunofluorescence and single cell transcriptomic analysis will be presented. Clinical trial information: NCT03737968.