Immutep Gains FDA Support for Eftilagimod Alfa Development in HNSCC Patients with Low PD-L1 Expression

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Immutep Limited, a biotechnology company focused on immunotherapy for cancer and autoimmune diseases, has received positive and constructive feedback from the U.S. Food and Drug Administration (FDA) regarding the late-stage clinical development of its lead product candidate, eftilagimod alfa (efti), in head and neck squamous cell carcinoma (1L HNSCC).¹

This regulatory support specifically pertains to first-line treatment of recurrent/metastatic HNSCC patients with PD-L1 expression levels below 1, a population with limited treatment options and high unmet medical need. About 20% of 1L HNSCC patients have CPS <1.² All currently available treatment options for patients with PD-L1 CPS <1 include chemotherapy.

The FDA's feedback stems from its review of data from TACTI-003 (KEYNOTE-C34), a phase 2b trial evaluating eftilagimod alfa in combination with anti-PD-1 pembrolizumab (Keytruda; Merck). The research focused on those whose tumors do not express PD-L1 (Combined Positive Score [CPS] <1). This patient group represents approximately 20% of patients diagnosed with 1L HNSCC, and currently lacks effective non-chemotherapy treatment options, as anti-PD-1 monotherapy is only approved for patients with PD-L1 CPS >1.

Encouraged by the trial results, the FDA acknowledged the potential of eftilagimod alfa in this key patient subtype and expressed support for further development of this combination treatment. The agency outlined two possible clinical pathways for Immutep to pursue. The first is a randomized registrational trial evaluating the combination therapy against standard-of-care options. Alternatively, Immutep can lead a single-arm study of about 70 to 90 patients with key endpoints regarding safety, response rate, and duration of response. This would be followed by a confirmatory randomized trial, potentially leading to accelerated approval.

“We are pleased with the FDA’s feedback and guidance that underscores the high unmet need of head and neck cancer patients whose PD-L1 expression level is below one. The FDA feedback positions Immutep to evaluate options for future collaborative clinical development paths to bring a new, effective and safe treatment option to this underserved patient population,” said Marc Voigt, CEO of Immutep. “Our primary focus clearly remains the pivotal TACTI-004 Phase III evaluating efti as first line therapy for non-small cell lung cancer and we are excited with its progress to date and the consistent, encouraging feedback we hear from physicians. This focus and additional considerations will be reviewed internally and discussed with stakeholders and potential strategic partners in regards to forward paths in head and neck cancer.”¹

These pathways align with the FDA Oncology Center of Excellence Project FrontRunner initiative, which aims to promote early access to promising cancer therapies by supporting their development in first-line settings rather than late-stage disease, where patients have already exhausted standard treatments. The initiative recognizes that advancing new treatments earlier in the disease course may significantly enhance patient outcomes.

References

1. Immutep Receives Positive Feedback from FDA on Late-Stage Clinical Development of Eftilagimod Alfa in Head and Neck Cancer with CPS <1. Press release. Immutep Limited. August 5, 2025. Accessed August 5, 2025. https://www.immutep.com/immutep-receives-positive-feedback-from-fda-on-late-stage-clinical-development-of-eftilagimod-alfa-in-head-and-neck-cancer-with-cps/

2. Chris M. Black et al. To test, or not to test, that is the question: A real-world analysis of PD-L1 expression testing patterns in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). JCO 41, 6033-6033(2023). DOI:10.1200/JCO.2023.41.16_suppl.6033