Xevinapant or Placebo Plus Platinum-Based Chemoradiotherapy in Unresected Locally Advanced Squamous Cell Carcinoma of the Head and Neck (TrilynX): A Randomized, Phase III Study.
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ICR Authors
Authors
Bourhis, J
Licitra, LF
Burtness, B
Psyrri, A
Haddad, R
Harrington, K
Cohen, EEW
Tao, Y
Tiscoski, KA
Matitashvili, A
Tahara, M
Sukari, A
Rutkowski, T
Salas, S
Nauwelaerts, H
Scheerlinck, R
Ha, N-T
Schroeder, A
Rodriguez-Gutierrez, A
Schoenfeld, JD
Licitra, LF
Burtness, B
Psyrri, A
Haddad, R
Harrington, K
Cohen, EEW
Tao, Y
Tiscoski, KA
Matitashvili, A
Tahara, M
Sukari, A
Rutkowski, T
Salas, S
Nauwelaerts, H
Scheerlinck, R
Ha, N-T
Schroeder, A
Rodriguez-Gutierrez, A
Schoenfeld, JD
Document Type
Journal Article
Date
2025-10-10
Date Accepted
2025-09-03
Abstract
PURPOSE: TrilynX was a randomized, double-blind, phase III study evaluating the addition of xevinapant (an inhibitor of apoptosis proteins inhibitor) or placebo to chemoradiotherapy (CRT) in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). METHODS: Patients with unresected LA SCCHN (oropharynx [p16-negative only], hypopharynx, or larynx) were randomly assigned 1:1 to six cycles of oral xevinapant 200 mg/day or matched placebo (once daily on Days 1-14 of a 21-day cycle) plus CRT for the first three cycles (cisplatin [100 mg/m2 once on Day 2 of every cycle] plus intensity-modulated radiotherapy [70 Gy; 35 fractions of 2 Gy/day, 5 days/week]). The primary end point was event-free survival (EFS) assessed by the blinded independent review committee. Progression-free survival, overall survival (OS), and safety were secondary end points. RESULTS: Between September 20, 2020, and February 27, 2023, 730 patients were randomly assigned to xevinapant plus CRT (n = 364) or placebo plus CRT (n = 366). The median (95% CI) EFS was 19.4 months (14.5 to not estimable) with xevinapant and 33.1 months (21.0 to not estimable) with placebo (hazard ratio [HR], 1.33 [95% CI, 1.05 to 1.67]; P = .9919). OS was worse in the xevinapant arm (HR, 1.39 [95% CI, 1.04 to 1.86]). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 320 (87.9%; xevinapant) and 286 (80.3%; placebo) patients; anemia (78 [21.4%] v 51 [14.3%]) and neutropenia (71 [19.5%] v 69 [19.4%]) were the most common. Serious TEAEs occurred in 194 (53.3%; xevinapant) and 129 (36.2%; placebo) patients. TEAEs leading to death occurred in 22 (6.0%; xevinapant) and 13 (3.7%; placebo) patients. CONCLUSION: Xevinapant plus CRT did not improve EFS (EFS was shorter with xevinapant v placebo) and demonstrated an unfavorable safety profile versus placebo plus CRT in patients with unresected LA SCCHN.
Citation
Journal of Clinical Oncology, 2025, 43 (29), pp. 3209 - 3220
Source Title
Journal of Clinical Oncology
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
0732-183X
eISSN
1527-7755
Collections
Research Team
Targeted Therapy