Immutep Limited announced positive results from Cohort B of the TACTI-003 (KEYNOTE-PNC-34) Phase IIb trial evaluating eftilagimod alfa (efti) in combination with MSD?s (Merck & Co. Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC) with negative PD-L1 expression. The updated efficacy and safety data was presented by Dr. Robert Metcalf during an oral presentation at the ESMO Virtual Plenary session at 18:30-19:30 CEST on July 11, 2024.

Results The investigational immuno-oncology (IO) combination utilising efti and KEYTRUDA achieved an objective response rate (ORR) of 35.5% (11 of 31 evaluable patients) and a disease control rate (DCR) of 58.1%, according to RECIST 1.1, in 1L HNSCC patients whose tumours do not express PD-L1 (Combined Positive Score [CPS] <1). These results are among the highest recorded for a chemotherapy-free approach in negative PD-L1 patients and compare favourably to a historical control of 5.4% ORR and 32.4% DCR from anti-PD-1 monotherapy. Additionally, the IO combination attained a high complete response rate of 9.7% (3 of 31 patients), which compares favourably to a historical control of 0% from anti-PD-1 monotherapy in 1L HNSCC patients with a CPS <1.2 Notably, one patient with early progressive disease according to RECIST 1.1 has evolved into a confirmed partial responder who remains on therapy after 14 months, resulting in a 38.7% ORR for the IO-combination, according to iRECIST.

Durability of responses is tracking well as has been seen in other clinical trials when efti is combined with KEYTRUDA. Over 50% of patients in Cohort B received treatment for at least six months with three additional patients nearing this threshold at the time of data cut off (11 March 2024). The combination also continues to have a favourable safety profile with no new safety signals observed.

This new data adds to the body of evidence that efti?s novel activation of antigen-presenting cells provides a strong boost to the immune system, enhancing the potential of immune checkpoint inhibitors such as KEYTRUDA. Importantly, as the only MHC Class II agonist in clinical development, efti is generating a broad anti-cancer immune response in a unique and safe manner across all levels of PD-L1 expression, especially in patients with negative expression (CPS <1). Next Steps: Based on the encouraging efficacy and high unmet medical need, Immutep will discuss the path forward with regulatory agencies.

Efti has received FDA Fast Track designation in 1L HNSCC regardless of PD-L1 expression. The prevalence for CPS <1, CPS 1-19, and CPS >20 PD-L1 expression levels are approximately 20%, 30%, and 50% of the HNSCC patient population, respectively.