Immutep Reports Positive Interim Results from Phase 2 Trial of LAG-3 Fusion Protein Eftilagimod Alpha Combined with Keytruda in NSCLC

Immutep Announces Positive Results from Phase 2 Trial of Eftilagimod Alpha (IMP321) in Collaboration with MSDRecently, Immutep, a biotechnology company focused on developing innovative immunotherapies for cancer and autoimmune diseases, announced that its soluble LAG-3 fusion protein, eftilagimod alpha (IMP321), achieved positive results in a Phase 2 clinical trial conducted in collaboration with MSD. An interim analysis of Cohort 1 in Part A of the trial, which included patients with previously untreated non-small cell lung cancer (NSCLC), demonstrated that a sufficient number of patients met the predefined response criteria. Based on these findings, the Data Monitoring Committee (DMC) has allowed Immutep to continue enrolling additional patients in this Phase 2 clinical trial.

LAG-3 protein can regulate the signaling pathways of T lymphocytes and antigen-presenting cells (APCs), playing a crucial role in adaptive immune responses. Soluble LAG-3 binds to major histocompatibility complex class II (MHC II) molecules on the surface of APCs, thereby activating these cells, which leads to an increase in the number and activation of cytotoxic CD8+ T cells. Through this mechanism, soluble LAG-3 protein enhances the immune response against cancer antigens.

Although Keytruda has been approved for the treatment of patients with non-small cell lung cancer (NSCLC), PD-L1 expression levels significantly influence whether patients can benefit from this therapy. Statistics show that the response rate to Keytruda is nearly 40% in NSCLC patients with PD-L1 expression >50%, whereas it is only 15–20% in those with PD-L1 expression levels of 1–49%. Patients lacking PD-L1 expression are expected to have an even lower response rate. Expanding the patient population that benefits from Keytruda therapy is one of MSD’s key research focuses. Soluble LAG-3 protein may enhance the efficacy of Keytruda by activating immune cell responses.

Image source: Immutep official website

Eftilagimod alpha is a soluble LAG-3 fusion protein. In the Phase 2 clinical trial named TACTI-002, it was used in combination with the PD-1 inhibitor Keytruda (pembrolizumab) to treat patients with various types of non-small cell lung cancer (NSCLC) and head and neck cancer. Patients in Cohort 1 of Part A of the trial were NSCLC patients who had never previously received Keytruda treatment. Enrollment in the trial did not depend on patients’ PD-L1 expression levels. The trial results showed that the combination of eftilagimod alpha and Keytruda achieved partial response in 7 out of 17 patients (41.2%), with an additional 6 patients achieving stable disease, resulting in a disease control rate of 76.5%. Currently, 12 patients continue to receive treatment.

Dr. Frederic Triebel, Chief Scientific Officer and Chief Manufacturing Officer at Immutep, stated, “We are pleased to observe that the early efficacy signals from Part A of the TACTI-002 clinical trial are consistent with a synergistic effect between eftilagimod alpha and Keytruda. We look forward to presenting more mature and detailed trial data at the SITC Annual Meeting in November.”

Image source: Immutep official website

In addition to activating APCs, LAG-3 expressed on the surface of T cells can inhibit T cell immune responses. Immutep is also developing a series of antibodies targeting LAG-3, which can modulate the function of LAG-3 on T cell surfaces from different perspectives. Among these, the antibody named IMP731 can bind to the LAG-3 protein on the surface of T cells, clearing recently activated T cells that accumulate around lesions in inflammatory diseases. This investigational therapy has been licensed to GlaxoSmithKline (GSK) for further development. Recently, GSK completed the first patient dosing in a Phase 2 clinical trial using IMP731 (also known as GSK2831781) for the treatment of ulcerative colitis (UC). As a result, Immutep received a milestone payment of £4 million.

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