Abstract CT150: Phase II study of spartalizumab (PDR001) vs chemotherapy (CT) in patients with recurrent/metastatic nasopharyngeal cancer (NPC)
Authors: Lim Darren Wan-Teck , Wang Hung-Ming , Li Shau-Hsuan , Ngan Roger , Dechaphunkul Arunee , Zhang Li , Yen Chia Jui , Chan Po Chung , Chakrabandhu Somvilai , Ma Brigette , Tanasanvimon Suebpong , Lee Victor , Lou Pei-Jen , Li Zujun , Spira Alexander , Sukari Ammar , Guigay Joël , McCune Steven , Sun Yongjian , Szpakowski Sebastian , Yao Yao , Fan Xueqiang , Manenti Luigi , Even Caroline 
Published: August 2019

Abstract
Background: There is currently no standard treatment for patients (pts) with platinum refractory, recurrent metastatic (R/M) NPC. Spartalizumab, a humanized anti-PD-1 IgG4 mAb, blocks interaction with PD-L1 and PD-L2. This is the first randomized phase II study to evaluate efficacy and safety of spartalizumab vs CT in NPC.
Methods: This phase II open-label study recruited pts with non-keratinizing locally advanced R/M NPC who progressed on/after platinum-based CT and received up to 2 systemic therapies. Pts were randomized (2:1) to receive spartalizumab or CT, per investigator’s choice. Spartalizumab was dosed 400 mg every 4 weeks intravenously. Pts in CT arm could cross over to receive spartalizumab if progression confirmed by RECIST v1.1, based on independent central review. Primary endpoint was progression free survival (PFS); secondary endpoints were overall response rate (ORR), based on central review by RECIST v1.1, duration of response (DOR), overall survival, safety and pharmacokinetics. Correlation between efficacy and expression of immunologic biomarkers and immune-related genes was also studied.
Results: In total, 76 pts in spartalizumab arm and 37 pts in CT arm were randomized (median age 51 years, ECOG performance status 0-2). As of Jan 31, 2018, 18/76 (23.7%) spartalizumab-treated pts, 8/37 (21.6%) CT-treated pts and 4/20 (20.0%) pts in crossover group were ongoing. Discontinuation rates were similar between arms, mainly due to progressive disease in spartalizumab arm (67.0%) and CT arm (68.0%). Median PFS (95% CI) was 1.9 mo (1.8;3.5) in spartalizumab arm vs 6.6 mo (3.7;9.2) in CT arm; primary endpoint was not met, with hazard ratio of 1.53 (95% CI 1.02;2.27). ORR (95% CI) was 18.4% (10.5;29.0) vs 32.4% (18.0;49.8) in spartalizumab vs CT arm, respectively, and 5.0% (0.1;24.9) in crossover group. ORR for pts treated with monotherapy CT was 19.2% (5/26) and for pts treated with CT doublet/triplet was 63.3% (7/11). The Kaplan-Meier estimate of DOR rate at 12 mo in responding spartalizumab-treated pts was 61.0% (95% CI 20.2;85.8). In CT arm, 11/12 pts either progressed or discontinued at 12 mo; at data cut-off, 1 pt remained responding for 3.61 mo. Safety profile of spartalizumab was largely consistent with results obtained from other spartalizumab single-agent studies. Overall, treatment-related grade 3/4 adverse events were reported in 18.4% of spartalizumab-treated pts and 40.5% of CT-treated pts. No treatment-related deaths occurred. RNA sequencing analyses of tumors revealed a correlation between response to spartalizumab and IFN-γ signature, TIM3 and LAG3 gene expression; this correlation was not observed in pts treated with CT.
Conclusions: Spartalizumab was well tolerated and despite the study not reaching its primary endpoint, long-lasting tumor responses were observed in a subset of spartalizumab-treated pts with NPC. Biomarker analysis is ongoing.
Citation Format: Darren Wan-Teck Lim, Hung-Ming Wang, Shau-Hsuan Li, Roger Ngan, Arunee Dechaphunkul, Li Zhang, Chia Jui Yen, Po Chung Chan, Somvilai Chakrabandhu, Brigette Ma, Suebpong Tanasanvimon, Victor Lee, Pei-Jen Lou, Zujun Li, Alexander Spira, Ammar Sukari, Joël Guigay, Steven McCune, Yongjian Sun, Sebastian Szpakowski, Yao Yao, Xueqiang Fan, Luigi Manenti, Caroline Even. Phase II study of spartalizumab (PDR001) vs chemotherapy (CT) in patients with recurrent/metastatic nasopharyngeal cancer (NPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT150.