Immutep’s Efti and KEYTRUDA® Show Positive Efficacy and Safety in First-Line Head and Neck Cancer

Immutep Limited, a clinical-stage biotechnology company, has revealed promising results from its Phase IIb TACTI-003 trial. The trial, which involves the combination of eftilagimod alpha (efti) and MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab), targets recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) as a first-line treatment. The data, current as of March 11, 2024, was presented at the European Society for Medical Oncology (ESMO) Congress 2024 by Claus Kristensen, M.D., Ph.D.

The trial results are particularly notable for patients with any level of PD-L1 expression, with the most significant outperformance seen in those with a Combined Positive Score (CPS) of 20 or higher. Efti, when combined with KEYTRUDA, achieved an Objective Response Rate (ORR) of 31.0%, which rose to 34.5% when including partial responses recorded after the data cut-off. This compares favorably to the 18.5% ORR seen with KEYTRUDA alone.

Additionally, the combination therapy demonstrated a high durability of response, maintaining a median Duration of Response (DOR) of 17.5 months in patients with any PD-L1 expression. The safety profile of the combination remains favorable, with no new safety signals observed, and the rate of discontinuation due to treatment-emergent adverse events was nearly identical between the combination therapy and KEYTRUDA alone.

A significant increase in absolute lymphocyte count (ALC) was observed in the combination therapy arm, indicating an effective immune response. This biological activity aligns with data from other Phase II trials where efti was combined with chemotherapy in metastatic breast cancer or with pembrolizumab in non-small cell lung cancer.

Dr. Claus Kristensen emphasized the potential of the novel immunotherapy combination, particularly for treating difficult-to-manage HNSCC. Dr. Frédéric Triebel, Chief Scientific Officer of Immutep, highlighted that the trial's results reinforce efti’s capability to enhance responses to immune checkpoint inhibitors, even in patients with negative PD-L1 expression.

Marc Voigt, CEO of Immutep, expressed optimism regarding the trial's outcomes and indicated plans to engage with regulatory authorities to discuss the path forward. The trial's results are crucial, especially given the high unmet need in this patient population. The primary endpoint of the study was the Objective Response Rate, with secondary endpoints including Overall Survival, which is expected to be assessed in 2025.

The TACTI-003 trial, also known as KEYNOTE-C34, is designed to evaluate the effectiveness of efti in combination with pembrolizumab versus pembrolizumab alone in patients with both PD-L1 positive (CPS ≥1) and PD-L1 negative (CPS <1) tumors. The data suggests a consistent and promising increase in ORR and DCR across various PD-L1 expression levels when efti is combined with pembrolizumab.

The results from TACTI-003 add to the growing body of evidence supporting the use of efti to enhance the immune system's response to cancer, particularly in combination with immune checkpoint inhibitors like KEYTRUDA. As the only MHC Class II agonist currently in clinical development, efti continues to show broad anti-cancer immune responses, benefiting patients with varying levels of PD-L1 expression.

Moving forward, Immutep will keep monitoring the maturing data from the TACTI-003 trial and discuss potential regulatory pathways. The continued success of efti in combination with KEYTRUDA could lead to meaningful advancements in the treatment of first-line head and neck cancer.