Immutep’s Efti Plus KEYTRUDA® Boosts Survival in Tough Head and Neck Cancer Cases

Context and Clinical Significance

Immutep Limited (ASX: IMM; NASDAQ: IMMP) has announced compelling mature data from its Phase IIb TACTI-003 trial, showing that its proprietary immunotherapy eftilagimod alfa (efti), when combined with Merck’s KEYTRUDA® (pembrolizumab), achieves a median overall survival (OS) of 17.6 months in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) exhibiting low PD-L1 expression (Combined Positive Score, CPS <1). This patient subgroup historically faces poor outcomes and limited treatment options, making these results particularly noteworthy.

Head and neck cancer patients with CPS <1 represent up to 20% of the first-line HNSCC population and are considered to have “cold tumors” that respond poorly to immunotherapy alone. Current standard treatments for this group typically involve chemotherapy combinations, which carry significant toxicity burdens. The TACTI-003 data thus signals a potential paradigm shift toward chemotherapy-free regimens in this difficult-to-treat cohort.

Comparative Efficacy and Safety Profile

The 17.6-month median OS observed with efti plus pembrolizumab markedly exceeds historical benchmarks: cetuximab plus chemotherapy yields about 10.7 months, anti-PD-1 therapy plus chemotherapy around 11.3 months, and anti-PD-1 monotherapy only 7.9 months. This more than doubling of survival compared to anti-PD-1 monotherapy underscores the complementary mechanism of action between efti, a soluble LAG-3 protein that activates antigen-presenting cells, and pembrolizumab, an established PD-1 checkpoint inhibitor.

Importantly, the combination therapy was well tolerated, with no new safety signals emerging. This safety profile, combined with multiple complete responses and a seven-fold increase in response rates, suggests a robust and durable clinical benefit. Such tolerability is critical for patients who often endure debilitating side effects from chemotherapy.

Regulatory and Commercial Outlook

Immutep has secured Fast Track designation from the FDA for efti in first-line HNSCC and has formally requested a meeting with the agency to discuss next steps and potential regulatory pathways. This proactive engagement signals confidence in the data and a strategic push toward approval. The company plans to continue patient follow-up and data analysis, with further updates expected later this year.

CEO Marc Voigt emphasized the unmet need in this patient population and the promise of a chemotherapy-free immunotherapy regimen. If approved, efti plus pembrolizumab could fill a critical gap in treatment, offering a more tolerable and effective option for patients with cold tumors who currently have no approved immunotherapy-only therapies.

Broader Implications and Next Steps

Beyond head and neck cancer, efti’s mechanism of stimulating both innate and adaptive immunity positions it as a versatile agent under evaluation in other solid tumors, including non-small cell lung cancer and metastatic breast cancer. The positive safety and efficacy signals here may bolster its broader clinical development and commercial potential.

Investors and analysts will be watching closely for the FDA meeting outcomes, additional trial data, and competitive developments in immuno-oncology. The evolving landscape for LAG-3 targeted therapies, combined with the growing demand for chemotherapy-free regimens, frames Immutep’s progress as a significant story in cancer treatment innovation.