Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial.

Abstract

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 IFNγ 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.

• Authors: Hans Wildiers, Anne Armstrong, Eveline Cuypere, Florence Dalenc, Luc Dirix, Steve Chan, Frederik Marme, Carolina P Schröder, Jens Huober, Francois P Duhoux, Peter Vuylsteke, Agnes Jager, Etienne Brain, Sherko Kuemmel, Zsuzsanna Pápai, Catharina Willemien Menke-van der Houven van Oordt, Luca Perjesi, Christian Mueller, Chrystelle Brignone, Frederic Triebel
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 30 Issue 3 Pg. 532-541 (02 01 2024) ISSN: 1557-3265 [Electronic] United States
• PMID: 37939105 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: ©2023 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Paclitaxel
• Receptor, ErbB-2

Topics

• Female
• Humans
• Middle Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (pathology)
• Disease-Free Survival
• Lymphocyte Activation
• Paclitaxel
• Quality of Life
• Receptor, ErbB-2 (metabolism)