Abstract CT124: Sitravatinib and nivolumab in oral cavity cancer window of opportunity study (SNOW)

摘要: Background: Squamous cell carcinoma of the oral cavity (SCCOC) often presents at early stages but its prognosis remains guarded, with a 5-year survival rate 60% despite curative-intent therapies. Preoperative window-of-opportunity (WOO) studies in resectable SCCOC enable pharmacodynamic evaluation molecular endpoints without compromising treatment. nivolumab was safe and showed promising tumor responses CheckMate-358 WOO study (Ferris et al. ESMO 2017, LBA46). Sitravatinib, receptor tyrosine kinase inhibitor which potently inhibits Tyro, AXL, Mer, VEGF family receptors, has shown encouraging results when combined non-small lung cancer patients who have progressed on anti-PD-1 agents (Leal 2018, 1129O). We hypothesize that sitravatinib synergistic antitumor immunogenic effects by increasing immune infiltration blocking oncogenic pathways implicated disease progression immune-checkpoint resistance. Methods: Trial design: SNOW is single-center, non-randomized preoperative SCCOC. Sitravatinib 120 mg given orally once daily from day 1 until 48h before surgery or for maximum period 28 days. Nivolumab 240mg intravenously 15 one dose only. Surgery planned between days 23-30 following treatment initiation. Fresh biopsies serial blood samples extensive immunophenotyping other biomarkers, as well clinical photographs tumor, are collected baseline, prior to time surgery. 18FAZA-PET scans performed baseline Key eligibility criteria: previously untreated SCCOC; T2-4a, N0-2 T1 (greater than cm)-N2; no history bleeding invasion major vessels; adequate organ function; autoimmune disorders; immunosuppressive therapy. Study objectives: primary objective evaluate plus nivolumab. Secondary objectives are: safety tolerability including toxicity, completion within window postoperative complications; activity complete pathological response; pharmacokinetics alone combination Correlative studies: immunophenotyping, genome transcriptome analysis, changes intratumoral hypoxia based testing. Sample size: proof-of-concept specific statistical assumptions trial onset. plan enroll 12-15 evaluable correlative studies. activation: Aug 30th, 2018. Two enrolled Jan 10th2019. Clinical identification: NCT03575598. Citation Format: Marc Oliva Bernal, Douglas Chepeha, Amy Prawira, Douglass Vines, Anna Spreafico, Scott Bratman, John De Almeida, Aaron Hansen, David Goldstein, Ralph Gilbert, Patrick Gullane, Dale H. Brown, Ilan Weinreb, Bayardo Perez-Ordonez, Pamela S. Ohashi, Tracy McGaha, Ben X. Wang, Jonathan Irish, Isan Chen, Lillian L. Siu. opportunity (SNOW) [abstract]. In: Proceedings American Association Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Res 2019;79(13 Suppl):Abstract nr CT124.