TY - JOUR
T1 - Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer
T2 - Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial
AU - Wildiers, Hans
AU - Armstrong, Anne
AU - Cuypere, Eveline
AU - Dalenc, Florence
AU - Dirix, Luc
AU - Chan, Steve
AU - Marme, Frederik
AU - Schröder, Carolina P.
AU - Huober, Jens
AU - Duhoux, Francois P.
AU - Vuylsteke, Peter
AU - Jager, Agnes
AU - Brain, Etienne
AU - Kuemmel, Sherko
AU - Pápai, Zsuzsanna
AU - der Houven van Oordt, Catharina Willemien Menke Van
AU - Perjesi, Luca
AU - Mueller, Christian
AU - Brignone, Chrystelle
AU - Triebel, Frederic
N1 - Publisher Copyright:
© 2023 The Authors; Published by the American Association for Cancer Research.
PY - 2024/2/1
Y1 - 2024/2/1
N2 - Purpose: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2– MBC). Patients and Methods: Women with HR+ HER2– MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers. Results: 114 patients received efti and 112 patients received placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197) but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFNg and CXCL10 levels. Conclusions: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. OS was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti’s role in patients with ET-resistant HER2– MBC.
AB - Purpose: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2– MBC). Patients and Methods: Women with HR+ HER2– MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers. Results: 114 patients received efti and 112 patients received placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197) but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFNg and CXCL10 levels. Conclusions: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. OS was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti’s role in patients with ET-resistant HER2– MBC.
UR - https://www.scopus.com/pages/publications/85184140486
U2 - 10.1158/1078-0432.CCR-23-1173
DO - 10.1158/1078-0432.CCR-23-1173
M3 - Article
C2 - 37939105
AN - SCOPUS:85184140486
SN - 1078-0432
VL - 30
SP - 532
EP - 541
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -
