Posted: 6 November 2023
Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announces new biomarker data from the TACTI-002/KEYNOTE-798 Phase II trial evaluating eftilagimod alpha (“efti”), a soluble LAG-3 protein and first-in-class MHC Class II agonist administered subcutaneously, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ., USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as first-line treatment for patients with previously untreated unresectable or metastatic non-small cell lung cancer (NSCLC).
The biomarker data related to blood samples from TACTI-002 patients to be presented at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting substantiates efti’s unique immune system stimulation and can be linked to its success in first line treatment of metastatic NSCLC patients, including the positive Overall Survival results recently reported at ESMO Congress 2023.
Dr Frederic Triebel, Immutep CSO, said, “Immunomonitoring of blood cells is of prime importance when one would like to understand the effect of a systemic immunostimulant injected subcutaneously, like efti is. Importantly, the pharmacodynamic data from efti in combination with pembrolizumab is associated with the 35.5-month median Overall Survival in first-line treatment of metastatic non-small cell lung cancer patients expressing PD-L1 (TPS >1%) that we recently reported at ESMO 2023. Similar to the immune response biomarker data seen in efti’s double-blind, randomized Phase IIb trial in HER2-/HR+ metastatic breast cancer, this data further confirms efti’s unique stimulation of the immune system, which may help patients live longer.”
Sustained and significant increase of interferon-gamma (IFN-γ) and C-X-C motif chemokine ligand 10 (CXCL10) serum biomarkers for systemic Th1 response were seen at three months and six months on-therapy. Among patients with a partial or complete response, 86% (6/7) showed a ≥1.4-fold change of IFN-γ and 100% (7/7) showed a ≥1.4-fold change CXCL10, after the first efti dosing.
Additionally, the early increase of absolute lymphocyte count (ALC) was significantly greater in patients that experienced a clinical benefit (e.g., overall survival, progression-free survival, complete response, partial response, stable disease), and is a potential on-treatment biomarker for response to this therapy. Furthermore, blood-based gene expression profiling (GEP) analyses revealed significant enrichment of genes involved in immune activation and cytotoxicity, including CD8 T cells, in patients with a favourable tumor response.
This biomarker data from the TACTI-002 Phase II is similar to the biomarker analysis from Immutep’s randomized, double-blind AIPAC Phase IIb trial in HER2-/HR+ metastatic breast cancer, which combined efti solely with paclitaxel chemotherapy and did not include any anti-PD-1 therapy. In that trial, the number of circulating immune cells (monocytes, activated CD8 T cells) and CXCL10 serum levels with efti increased in a statistically significant fashion compared to baseline. The increase in pharmacodynamic markers, including ALC and CD8 T Cells, were also significantly linked to improved overall survival in the efti group.
The poster titled “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” will be available on the Posters & Publications section of Immutep’s website following its presentation. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
