TY - JOUR
T1 - Bintrafusp Alfa With CCRT Followed by Bintrafusp Alfa Versus Placebo With CCRT Followed by Durvalumab in Patients With Unresectable Stage III NSCLC
T2 - A Phase 2 Randomized Study
AU - Vokes, Everett E.
AU - Mornex, Francoise
AU - Sezer, Ahmet
AU - Cheng, Ying
AU - Fang, Jian
AU - Baz, David Vicente
AU - Cil, Timucin
AU - Adjei, Alex A.
AU - Ahn, Myung Ju
AU - Barlesi, Fabrice
AU - Felip, Enriqueta
AU - Garon, Edward B.
AU - Audhuy, Francois
AU - Ito, Rena
AU - Sato, Masashi
AU - Eggleton, S. Peter
AU - Martin, Claudio Marcelo
AU - Reck, Martin
AU - Robinson, Clifford G.
AU - Paz-Ares, Luis
N1 - Publisher Copyright:
© 2023 International Association for the Study of Lung Cancer
PY - 2024/2
Y1 - 2024/2
N2 - Introduction: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment. Methods: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. On the basis of the recommendation of an independent data monitoring committee, the study was discontinued before the maturity of overall survival data (secondary end point). Results: A total of 153 patients were randomized to either BA (n = 75) or durvalumab groups (n = 78). The median progression-free survival was 12.8 months versus 14.6 months (stratified hazard ratio = 1.48 [95% confidence interval: 0.69–3.17]), in the BA and durvalumab groups, respectively. Trends for overall response rate (29.3% versus 32.1%) and disease control rate (66.7% versus 70.5%) were similar between the two groups. Any-grade treatment-emergent adverse events occurred in 94.6% versus 96.1% of patients in the BA versus durvalumab groups, respectively. Bleeding events in the BA group were mostly grade 1 (21.6%) or 2 (9.5%). Conclusions: BA with cCRT followed by BA exhibited no efficacy benefit over placebo with cCRT followed by durvalumab in patients with stage III unresectable NSCLC.
AB - Introduction: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment. Methods: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. On the basis of the recommendation of an independent data monitoring committee, the study was discontinued before the maturity of overall survival data (secondary end point). Results: A total of 153 patients were randomized to either BA (n = 75) or durvalumab groups (n = 78). The median progression-free survival was 12.8 months versus 14.6 months (stratified hazard ratio = 1.48 [95% confidence interval: 0.69–3.17]), in the BA and durvalumab groups, respectively. Trends for overall response rate (29.3% versus 32.1%) and disease control rate (66.7% versus 70.5%) were similar between the two groups. Any-grade treatment-emergent adverse events occurred in 94.6% versus 96.1% of patients in the BA versus durvalumab groups, respectively. Bleeding events in the BA group were mostly grade 1 (21.6%) or 2 (9.5%). Conclusions: BA with cCRT followed by BA exhibited no efficacy benefit over placebo with cCRT followed by durvalumab in patients with stage III unresectable NSCLC.
KW - Bifunctional
KW - Bintrafusp alfa
KW - Concurrent chemoradiotherapy
KW - Non–small cell lung cancer
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=85176260549&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2023.09.1452
DO - 10.1016/j.jtho.2023.09.1452
M3 - Article
C2 - 37797733
AN - SCOPUS:85176260549
SN - 1556-0864
VL - 19
SP - 285
EP - 296
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 2
ER -