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 2b Trial
AU - Wildiers, Hans
AU - Armstrong, Anne
AU - Cuypere, Eveline
AU - Dalenc, Florence
AU - Dirix, Luc
AU - Chan, Stephen
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 - Menke-van der Houven van Oordt, Catharina Willemien
AU - Perjesi, Luca
AU - Mueller, Christian
AU - Brignone, Chrystelle
AU - Triebel, Frederic
PY - 2023/11/8
Y1 - 2023/11/8
N2 - PURPOSE: Eftilagimod alpha (efti), a soluble LAG-3 protein and MHC class II agonist, enhances innate and adaptive immunity. 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, 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 IFN-γ and CXCL10 levels.CONCLUSIONS: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. Overall survival 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 LAG-3 protein and MHC class II agonist, enhances innate and adaptive immunity. 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, 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 IFN-γ and CXCL10 levels.CONCLUSIONS: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. Overall survival 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.
U2 - https://doi.org/10.1158/1078-0432.CCR-23-1173
DO - https://doi.org/10.1158/1078-0432.CCR-23-1173
M3 - Article
C2 - 37939105
SN - 1078-0432
JO - Clinical cancer research : an official journal of the American Association for Cancer Research
JF - Clinical cancer research : an official journal of the American Association for Cancer Research
ER -