FDA Backs Immutep's Eftilagimod Alfa for Head and Neck Cancer Treatment in Patients with Low PD-L1 Expression

Immutep has received positive feedback from the FDA on its late-stage clinical development of eftilagimod alfa in head and neck cancer patients with CPS <1. The FDA recommends a randomized registrational trial or a smaller single-arm study followed by a confirmatory study. This development aligns with the FDA's Project FrontRunner initiative, focusing on patients with unmet medical needs, such as the 20% of first-line HNSCC patients with CPS <1. Immutep's efti, a first-in-class MHC Class II agonist, could offer a chemotherapy-free immunotherapy option when combined with pembrolizumab.

Title: Immutep's Eftilagimod Alfa Receives Positive Feedback from FDA for Head and Neck Cancer Treatment

Sydney, Australia, July 2, 2025 — Immutep Limited (ASX: IMM; NASDAQ: IMMP), a late-stage immunotherapy company targeting cancer and autoimmune diseases, has received positive and constructive feedback from the US Food and Drug Administration (FDA) regarding the late-stage clinical development of its first-in-class MHC Class II agonist, eftilagimod alfa (efti), for first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (1L HNSCC) patients with PD-L1 expression below 1 (Combined Positive Score [CPS] 1) [1].

Based on the encouraging data from the TACTI-003 (KEYNOTE-C34) Phase IIb trial evaluating efti in combination with Merck & Co., Inc.'s (Rahway, NJ, USA) anti-PD-1 KEYTRUDA® (pembrolizumab), the FDA has agreed on the potential of efti in combination with KEYTRUDA to address the high unmet need in this CPS 1 patient segment and is supportive of the combination’s further development [1]. The FDA has outlined two potential development paths: a randomized registrational trial evaluating efti in combination with KEYTRUDA against standard-of-care therapy or a smaller single-arm study (e.g., 70 - 90 patients) with safety, response rate, and duration of response as key endpoints, followed by a confirmatory randomized study that builds on the existing data [1].

The FDA's feedback aligns with its Project FrontRunner initiative, which encourages drug sponsors to develop and seek approval of cancer drugs for advanced/metastatic disease in earlier clinical settings rather than waiting until patients have exhausted other treatment options. This initiative aims to significantly improve the quantity and quality of patients' lives [1].

Immutep's CEO, Marc Voigt, stated, "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" [1].

The company notes that up to 20% of 1L HNSCC patients have CPS 1, representing a significant unmet medical need. Currently, all treatment options for these patients include chemotherapy. Efti, a first-in-class MHC Class II agonist, appears to complement pembrolizumab's PD-1 inhibition, potentially offering these low PD-L1 expressing patients an immunotherapy option without chemotherapy [1].

While Immutep's primary focus remains on its Phase III lung cancer trial (TACTI-004), the FDA feedback creates valuable optionality for the company's clinical development strategy and potential partnerships. This development signals the agency's recognition of both the unmet need and efti's potential to address it.

References:
[1] 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/