Combination of eftilagimod alpha and pembrolizumab effective against refractory NSCLC

April 2023 Cancer trials Robin van Amersfoort

The Australian biotechnology company Immutep Limited, has presented positive final data from the phase II clinical trial TACTI-002 at the European Lung Cancer Congress 2023. The trial aimed to determine the effectiveness of eftilagimod alpha (efti), in combination with pembrolizumab, an anti-PD-L1 therapy, to treat metastatic non-small cell lung cancer patients who had previously failed treatment with anti-PD-L1 therapy. Patients receiving the combination of efti and pembrolizumab had a 21-months OS rate of 39%, which compares favourably to typical 10-15% OS rate for standard-of-care chemotherapy.


Non-small cell lung cancer (NSCLC) is a debilitating disease with a low survival rate. While recent advances in immunotherapy with anti-PD-L1 drugs have led to improved outcomes, a proportion of NSCLC patients does not benefit from this treatment modality.1 As such, there is a need for new and more effective therapies to treat advanced NSCLC. Efti is a soluble lymphocyte activation gene-3 (LAG-3) protein. It is a first-in-class antigen presenting cell (APC) activator that stimulates both innate and adaptive immunity for the treatment of cancer. Efti binds to and activates antigen-presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer. Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), metastatic melanoma, and metastatic breast cancer.2,3


The phase II trial TACTI-002 enrolled a total of 36 NSCLC patients with confirmed disease progression who previously failed treatment with anti-PD-L1 therapy. The primary objective of the study was to determine the overall response rate (ORR) of the two treatment groups, while secondary objectives included progression-free survival (PFS), overall survival (OS), and safety assessments.


The combination of efti plus pembrolizumab achieved a median Overall Survival (mOS) of 9.9 months with a 39% OS rate at 21 months. This compares favourably to typical 6-9 months mOS and a 10-15% 21 month OS-rate obtained with standard-of-care chemotherapy in this setting. Additionally, 83.3% of patients showed shrinkage (33%) or deceleration of tumour growth (50%). Efti plus pembrolizumab came with an ORR of 8.3%  and a 6-month PFS rate of 25% in all-comer PD-L1 patient population with 75% of patients having negative or low PD-L1 expression. In patients with high PD-L1 expression the ORR was higher at 33.3%, with a 6-month PFS rate of 50%. Efti plus pembrolizumab was well tolerated without any new safety signals, and there was no treatment discontinuation due to adverse reactions.


Overall, the positive results from the TACTI-002 trial identify efti as a promising new treatment option for patients with advanced NSCLC who failed previous treatment with anti-PD-L1 therapy.. The combination of efti and pembrolizumab has significant potential to safely improve outcomes for NSCLC patients.


  1. O’Brien M, Paz-Ares L, Marreaud S, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274-1286.
  2. Atkinson V, Khattak A, Haydon A, et al. Eftilagimod alpha, a soluble lymphocyte activation gene-3 (LAG-3) protein plus pembrolizumab in patients with metastatic melanoma. J Immunother Cancer. 2020;8(2):e001681.
  3. Dirix L, Triebel F. AIPAC: a Phase IIb study of eftilagimod alpha (IMP321 or LAG-3Ig) added to weekly paclitaxel in patients with metastatic breast cancer. Future Oncol. 2019;15(17):1963-1973.