Immutep Limited (ASX: IMM; NASDAQ: IMMP) has released new biomarker data from its TACTI-002/KEYNOTE-798 Phase II trial, in which they investigated eftilagimod alpha ("efti"), a soluble LAG-3 protein and first-in-class MHC Class II agonist administered subcutaneously. This trial examined efti in conjunction with MSD's (Merck & Co., Inc., Rahway, NJ., USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as the initial treatment for patients with unresectable or metastatic non-small cell lung cancer (NSCLC).

The recent presentation of biomarker data, presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2023, supports efti's unique ability to stimulate the immune system. This immune system activation is closely associated with its success in treating first-line metastatic NSCLC patients, as demonstrated by the positive Overall Survival results reported at the ESMO Congress 2023.

Immutep, highlighted the importance of immunomonitoring of blood cells in comprehending the effects of a subcutaneously administered systemic immunostimulant like efti. He emphasized the connection between the pharmacodynamic data from efti combined with pembrolizumab and the 35.5-month median Overall Survival achieved in first-line treatment of metastatic non-small cell lung cancer patients expressing PD-L1 (TPS >1%), as reported at ESMO 2023. Similar to the immune response biomarker data observed in efti's Phase IIb trial in HER2-/HR+ metastatic breast cancer, this data reinforces efti's unique immune system stimulation, which could extend the lives of patients.

The data revealed a sustained and significant increase in interferon-gamma (IFN-γ) and C-X-C motif chemokine ligand 10 (CXCL10) serum biomarkers for systemic Th1 response at three and six months during therapy. Notably, patients with a partial or complete response exhibited significant increases in IFN-γ and CXCL10 after the first efti dosing.

Furthermore, the early rise in absolute lymphocyte count (ALC) was significantly higher in patients experiencing clinical benefits, making it a potential biomarker for treatment response. Blood-based gene expression profiling (GEP) analyses showed significant enrichment of genes associated with immune activation and cytotoxicity, including CD8 T cells, in patients who responded favorably to the treatment.

This biomarker data from the TACTI-002 Phase II trial parallels the biomarker analysis from Immutep's AIPAC Phase IIb trial in HER2-/HR+ metastatic breast cancer. In the AIPAC trial, efti was combined solely with paclitaxel chemotherapy and did not include any anti-PD-1 therapy. In that study, efti demonstrated a statistically significant increase in the number of circulating immune cells (monocytes and activated CD8 T cells) and CXCL10 serum levels compared to baseline. The enhancement of pharmacodynamic markers, including ALC and CD8 T Cells, was also significantly linked to improved overall survival in the efti group.

Efti is a proprietary soluble LAG-3 protein and MHC Class II agonist developed by Immutep for cancer treatment. It activates both innate and adaptive immunity and binds to MHC Class II molecules on antigen presenting cells (APCs), leading to the activation and proliferation of various immune cell types. Efti also upregulates the expression of key biological molecules like IFN-γ and CXCL10, which further enhance the immune system's ability to combat cancer. Efti is being evaluated for various solid tumors, including NSCLC, HNSCC, and metastatic breast cancer. Its favorable safety profile allows for various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy, and it has received Fast Track Designation from the FDA for first-line HNSCC and first-line NSCLC.

 

Source: globenewswire.com

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