Biomarker and multivariate analyses results from AIPAC: A phase IIb study comparing eftilagimod alpha (a soluble LAG-3 protein) vs placebo in combination with weekly paclitaxel in HR+HER2-metastatic breast cancer
Marme, F. Wildiers, H. Dirix, L. Armstrong, Anne C De Cuypere, E. Dalenc, F. Schroder, C. P. Vuylsteke, P. Brain, E. Kuemmel, S.
Marme, F.
Wildiers, H.
Dirix, L.
Armstrong, Anne C
De Cuypere, E.
Dalenc, F.
Schroder, C. P.
Vuylsteke, P.
Brain, E.
Kuemmel, S.
Citations
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Abstract
Background: Eftilagimod alpha (EF) is a soluble LAG-3 protein (LAG-3Ig) that binds to
a subset of MHC class II molecules and mediates activation of antigen-presenting cells
followed by T-cells. AIPAC investigated EF + paclitaxel (PA). We hereby report
exploratory biomarker and multivariate analyses.
Methods: This double-blinded, 1:1 randomized phase IIb trial enrolled pts with HR+
HER2- MBC. Pts received PA (80 mg/m2 IV on D1, D8, D15) + EF (30 mg) or placebo
(PL) on D2, D16 per cycle (28 days) for 24 wks + EF/PL for 52 wks. Exploratory EPs
were potential biomarkers and their correlation to efficacy. Multivariate analysis used
backward selection p>0.15 (univariate cox model). Blood cell subsets (CD4; CD8,
PBMCs, monocytes) & Th1 biomarker CXCL-10 were measured centrally. Comparison
was done using 2-sided Wilcoxon test.
Results: 226 pts [efti n¼114; placebo n¼112] were included. Pts were endocrine
resistant (84%), pre-treated with CDK4/6 inhibitors (44.2%). Post-study treatment was
similar. Safety/efficacy were reported at SABCS 2020 #132; SITC 2021 #948 In the
multivariate predictive model 4 groups (high Neutrophil/Lymphocyte Ratio [NLR]; no
prior taxanes; low monocytes and <5 yrs since diagnosis) were significant for OS
(Table) On treatment mean fold-changes of monocytes (5.81 vs. 2.29; p¼0.025),
PBMCs (2.00 vs. 1.41; p¼0.041), T cells (2.28 vs. 1.48; p¼0.086), & CXCL10 (2.78 vs.
1.56; p¼0.06) were significantly higher (EF vs PL) and linked to higher OS. Post
baseline CD4 (median 896/ml vs. 736 ml; p¼0.038) & CD8 (median 377/ml vs. 223 ml;
p¼0.005) T cell count increased significantly in pts with higher OS EF vs. PL.
Conclusions: EF + PA elicits significant effects on different immune cells which is
significantly associated with higher OS. Multivariate analysis identified potential traget populations for phase III.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Marmé F, Wildiers H, Dirix L, Armstrong A, De Cuypere E, Dalenc F, et al. 171P Biomarker and multivariate analyses results from AIPAC: A phase IIb study comparing eftilagimod alpha (a soluble LAG-3 protein) vs placebo in combination with weekly paclitaxel in HR+ HER2- metastatic breast cancer. Vol. 33, Annals of Oncology. Elsevier BV; 2022. p. S203–4.