Combination of eftilagimod alpha and pembrolizumab effective against refractory NSCLC

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.

Introduction

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

Methods

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.

Results

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.

Conclusion

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.

References

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.