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595 Biomarker results from the 1st line non-small cell lung cancer cohort of TACTI-002: pharmacodynamic effects of combining eftilagimod alpha (soluble LAG-3) and pembrolizumab
  1. Martin Forster1,
  2. Enriqueta Felip2,
  3. Margarita Majem3,
  4. Bernard Doger4,
  5. Tim Clay5,
  6. Enric Carcereny6,
  7. Igor Bondarenko7,
  8. Julio Peguero8,
  9. Manuel Cobo Dols9,
  10. Grygorii Ursol10,
  11. Ewa Kalinka11,
  12. Gema Garcia Ledo12,
  13. Laia Vilà Martinez13,
  14. Matthew Krebs14,
  15. Wade T Iams15,
  16. Christian Mueller16,
  17. Chrystelle Brignone17 and
  18. Frederic Triebel17
  1. 1UCL/University College London NHS, London, UK
  2. 2Vall D’Hebron University Hospital, Barcelona, Spain
  3. 3Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  4. 4START Madrid – fundacion Jimenez Diaz, Madrid, Spain
  5. 5St John of God Subiaco Hospital, Perth, Western Australia, Australia
  6. 6Catalan Institute of Oncology Badalona-Hospital Germans Trias i Pujol, B-ARGO group, Badalona, Spain
  7. 7Dnipro Medical University, Dnipro, Dnipropetrovsk Oblast, Ukraine
  8. 8Oncology Consultants, Houston, TX, USA
  9. 9Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain
  10. 10St. Luke’s Hospital – Medical and Diagnostic Center ‘Acinus’’, Kropyvnytskyi, Ukraine
  11. 11Instytut Centrum Zdrowia Matki Polki, Lodz, Poland
  12. 12HM Universitario Sanchinarro, Madrid, Spain
  13. 13Parc Taulí Sabadell Hospital Universitari, Barcelona, Spain
  14. 14Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK
  15. 15Vanderbilt University Medical Center, Nashville, TN, USA
  16. 16Immutep GmbH, Berlin, Germany
  17. 17Immutep S.A.S., Chatenay-Malabry, France
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Eftilagimod alpha (E, LAG-3Ig) is a soluble LAG-3 protein binding to MHC class II and stimulates antigen-presenting cells (APC). Thus T cells (CD4/CD8) are recruited, leading to stronger anti-tumor response than with pembrolizumab (P). Clinical studies with E have shown increased IFN-gamma, CXCL10 and absolute lymphocyte count (ALC). We report biomarker results from the 1st line non-small cell lung carcinoma (NSCLC) cohort in TACTI-002 (NCT03625323).

Methods Pts with measurable, 1st line metastatic NSCLC unselected for PD-L1 were recruited. Exploratory endpoints included analyses of Th1 biomarkers (IFN-gamma; CXCL10), ALC and gene expression profile (GEP). Pts received E (30 mg SC q2w 8 cycles [1 cycle= 3 weeks], then q3w) with P (200 mg IV q3w). Th1 samples were collected early (pre-dose; 8x within 96 h) and late (pre-dose at 3 and 6 mts). Th1 levels were assessed centrally by electrochemiluminescence immunoassay. ALC was locally tested on day 1 of each cycle. GEP samples were collected (pre-treatment and at 3 mts) for central testing (Nanostring nCounter® PanCancer Immune Profiling Panel).

Results 114 pts were enrolled. Median age was 67 yrs (44–85) & 74% were male. ECOG PS was 0 & 1 in 37% & 63% of pts. IFN-gamma and CXCL10 significantly increased soon after first E administration (up to 96 h; table 1) and remained significantly elevated at 3 and 6 mts (table 1) pre-dose.

ALC increase from baseline was observed at 1st assessment and was maintained. When separating pts by disease control (CR, PR & SD versus PD, NA & NE, by iRECIST), ALC change was significantly higher in pts with disease control (0.43 vs 0.04; p=0.01). PFS was significantly prolonged in pts with ALC increase (≥0.2 versus <0.2x109/L pre-defined cut-off), on treatment (mPFS 9.8 mts vs. mPFS 6.9 mts, respectively). OS was immature at data cut-off (31-Mar-23).

GEP analysis showed upregulated expression of genes related to T-cell functions, cytotoxicity functions, cytotoxic cells, or TH1 cells which are more pronounced in pts with PR/CR.

Conclusions Significant early and sustained increases of circulating biomarkers and ALC substantiate the systemic stimulation via the APC activator efti and show that repeated minimally-invasive liquid biopsies, i.e., blood samplings, are key in detecting this systemic stimulation.

Acknowledgements We thank all the participating patients & their families. We thank the dedicated clinical trial investigators & their team members. This study is sponsored by Immutep. Corresponding author: Frederic Triebel, This study is in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Trial RegistrationThe trial identifiers are TACTI-002 (sponsor code), IMP321-P015 (Sponsor code),Keynote-PN798 (MSD code), 2018–001994-25 (EudraCT) and NCT03625323 (

Abstract 595 Table 1

Mean fold change from baseline of IFN-gamma and CXCL10 at various timepoints

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