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948 Final results from AIPAC: A phase IIb comparing eftilagimod alpha (a soluble LAG-3 protein) vs. placebo in combination with weekly paclitaxel in HR+ HER2- MBC
  1. Hans Wildiers1,
  2. Luc Dirix2,
  3. Anne Armstrong3,
  4. Eveline De Cuypere4,
  5. Florence Dalenc5,
  6. Steven Chan6,
  7. Frederik Marme7,
  8. Carolina Pia Schröder8,
  9. Jens Huober9,
  10. Peter Vuylsteke10,
  11. Jean-Philippe Jacquin11,
  12. Etienne Brain12,
  13. Sherko Kümmel13,
  14. Zsuzsanna Pápai14,
  15. Christian Mueller15,
  16. Chrystelle Brignone15 and
  17. Frederic Triebel15
  1. 1University Hospitals Leuven; Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven, Belgium
  2. 2GZA Ziekenhuizen campus Sint-Augustin, Oosterveldlaan, Belgium
  3. 3The Christie NHS Foundation Trust, Manchester, UK
  4. 4AZ Sint-Jan Brugge-Oostende AV, Ruddershove, Belgium
  5. 5Institut Claudius Regaud (Institut Claudius regaud- Institut Universitaire du Cancer – Oncopole), Toulouse, France
  6. 6Nottingham Cancer Clinical Trials Team, Nottingham, UK
  7. 7National Center for Tumor Diseases (NCT), Heidelberg, Germany
  8. 8University Medical Center Groningen, Groningen, Netherlands
  9. 9Universitätsfrauenklinik Ulm, Ulm, Germany
  10. 10CMSE UCLouvain, CHU UCL NAMUR Site Ste-Elisabeth, AND University of Botswana, Uccle, Belgium
  11. 11Institut de Cancérologie de la Loire, Saint Priest en Jarez, France
  12. 12Institut Curie -Hôpital René Huguenin, Saint-Cloud, France
  13. 13KEM | Evang. Kliniken Essen-Mitte, Essen, Germany
  14. 14MH Egészségügyi Központ Onkológiai, Budapest, Hungary
  15. 15Immutep, Berlin, Germany


Background Eftilagimod alpha (efti; IMP321) 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 CD8 T-cells. Weekly paclitaxel is a standard of care chemo-regimen after failure of endocrine-based therapy for metastatic breast carcinoma (MBC). AIPAC (Active Immunotherapy PAClitaxel) investigated the addition of efti to weekly paclitaxel in these patients (pts).

Methods This placebo-controlled, double-blinded, 1:1 randomized phase IIb trial enrolled pts with measurable disease, HR+ HER2- MBC after endocrine-based therapy. Pts received paclitaxel (80 mg/m² IV on D1, D8, D15) + efti (30 mg) or placebo on D2, D16 (every 2 weeks) for up to 24 weeks following efti/placebo for up to 52 weeks. The primary endpoint (EP) was progression-free survival (RECIST1.1) by BICR. Secondary EPs included overall survival (OS), PFS (local read), overall response rate (ORR), biomarker, quality of life. Exploratory EPs included univariate/multivariate analyses.

Results 227 pts were randomized (Jan2017-Jul2019). All except 1 received ≥1 treatment and were included in the full analysis set [efti (n=114); placebo (n=112)]. Data cut-off was 14May2021 (min. follow-up= 22 months). Median age was 60 yrs with ECOG 0 in 61.5%. 91.6% had visceral disease. Pts were mostly endocrine resistant (84%) and partially pre-treated with CDK4/6 inhibitors (44.2%). Post-study treatment was similar. Median OS was 20.4 (95% CI: 14.3-25.1) months in the efti group vs. 17.5 (95% CI: 12.9-21.9) in the placebo group. HR was 0.88 (95%CI: 0.64-1.19; p=0.197). In predefined univariate analyses, younger pts, low baseline monocytes and luminal B showed significant/clinically meaningful improvement in OS (table 1).

Efti increased PBMC/T cell (CD4/CD8) count vs. placebo, correlating with improved OS (Spearman Rho=0.6, p=0.02 for CD8 T cells). In a whole population multivariate cox regression model, increasing BMI and prior treatment with CDK4/6 were independent significant poor prognostic markers for PFS and OS.

TEAEs leading to discontinuation were similar at 5.3%(efti) & 6.3%(placebo). PFS (Primary EP) and safety were reported at SABCS 2020 (Abstract#132).

Abstract 948 Table 1

Overall survival by subgroups at final analysis

Conclusions Efti added to paclitaxel led to a non-significant 2.9 months median OS increase in HR+ HER2- MBC pts after endocrine-based therapy. Effects were significant in pts <65yrs, with low monocytes and more aggressive disease (luminal B). Efti increased circulating CD4/CD8 T cells, which significantly correlated to improved OS. Weekly paclitaxel + efti should be further investigated in MBC.

Trial Registration The trial identifiers are IMP321-P011 (code for sponsor), 2015-002541-63 (EudraCT) and NCT02614833 (

Ethics Approval The study was approved by relevant ethic committees and institutional review boards.

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