Phase 2 study of xevinapant + chemoradiotherapy (CRT) vs placebo + CRT in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN): A post hoc activity analysis by blinded independent review committee evaluation.

Abstract

e18039 Background: The randomized, placebo-controlled, double-blind, phase 2 study (NCT02022098) of xevinapant + CRT demonstrated for the first time improved efficacy outcomes, including 5-year overall survival, when adding a new treatment modality to CRT for patients (pts) with unresected LA SCCHN. Here, we report a post hoc analysis comparing selected efficacy endpoints by blinded independent review committee (BIRC) evaluation with previously reported outcomes by investigator analysis. Methods: The study design was previously published (Sun X-S, et al. Lancet Oncol. 2020;21[9]:1173-87). Pts received oral xevinapant 200 mg/day (Days 1–14 of a 21-day cycle for 3 cycles), or matched placebo, with standard-of-care cisplatin-based CRT. Progression-free survival (PFS), duration of response (DOR), best overall response (BOR), and time to response (TTR) were independently evaluated by a two-reader, sequential time point presentation, batch read mode paradigm. Radiologists were blinded to investigator assessments. Discrepancies were adjudicated by a blinded, independent third radiologist. Results: All 96 pts randomized into the study (n=48 in each arm) were evaluated by BIRC. Response concordance between BIRC and investigator assessment was 84.4%. There were 31 PFS events by BIRC (xevinapant + CRT, 11 events; placebo + CRT, 20 events) and 38 PFS events by investigator (xevinapant + CRT, 12 events; placebo + CRT, 26 events) assessment, respectively. Xevinapant + CRT reduced the risk of disease progression (by BIRC) or death vs placebo + CRT by 62% (HR, 0.38 [95% CI, 0.18–0.79]; p=0.0099); median PFS was not reached (NR) vs 20.8 months, respectively. PFS outcomes by investigator analysis (HR, 0.33; 95% CI, 0.17–0.67; p=0.0019) were similar. DOR (by BIRC) was prolonged with xevinapant + CRT vs placebo + CRT (median, NR vs 31.4 months; HR, 0.31 [95% CI, 0.11–0.83]; p=0.0196), which was similar to outcomes by investigator analysis (adjusted HR, 0.21; 95% CI, 0.08–0.54; p=0.0011). Complete response (CR; by BIRC) was the most frequent BOR in both arms (xevinapant + CRT, 28 [58.3%]; placebo + CRT, 19 [39.6%]); the CR rate was greater in pts treated with xevinapant + CRT vs pts treated with placebo + CRT (odds ratio, 2.56; 95% CI, 1.07–6.13; p=0.0344). The CR rate trends by BIRC evaluation were similar to those by investigator analysis (xevinapant + CRT, 31 [64.4%]; placebo + CRT, 26 [54.2%]). A difference in TTR (by BIRC) favoring xevinapant + CRT over placebo + CRT was also observed (HR, 0.65 [95% CI, 0.39–1.07]). Conclusions: While fewer PFS events were observed by BIRC than by investigator assessment, the BIRC results were generally consistent with those of the investigators, with only minor differences in endpoint outcomes. Clinical trial information: NCT02022098 .