FDA Outlines Next Steps for Development of Eftilagimod Alfa in PD-L1–Negative HNSCC

The FDA has issued feedback to Immutep regarding the next steps of the future clinical development of eftilagimod alfa for the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have a PD-L1 combined positive score (CPS) of less than 1.1

Immutep, the developer of eftilagimod alfa, announced that the FDA was aligned regarding the potential of eftilagimod alfa in combination with pembrolizumab (Keytruda) to address an unmet need in the frontline setting in this patient population, based on data from the phase 2b TACTI-003/KEYNOTE-C34 trial (NCT04811027).

Potential accelerated approval of the combination through the FDA’s Project Frontrunner initiative could be sought using a randomized registrational trial evaluating eftilagimod alfa plus pembrolizumab vs standard-of-care therapy; or via a smaller single-arm study with overall response rate (ORR), duration of response (DOR), and safety end points, followed by a randomized confirmatory trial.

“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 1,” Marc Voigt, chief executive officer of Immutep, stated in a news release. “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.”

TACTI-003 Data

Findings from cohort B of the phase 2b trial presented at the 2024 ESMO Immuno-Oncology (IO) Congress showed that efficacy-evaluable patients (n = 31) experienced an ORR of 35.5% (95% CI, 19.2%-54.6%) per RECIST 1.1 criteria, including a complete response (CR) rate of 12.9% and a partial response (PR) rate of 22.6%.2 The rates of stable disease (SD) and progressive disease (PD) were 22.6% and 41.9%, respectively; the disease control rate (DCR) was 58.1% (95% CI, 39.1%-75.5%).

Per iRECIST criteria, the ORR was 38.7% (95% CI, 21.8%-57.8%) with respective CR and PR rates of 16.1% and 22.6%. The SD rate, PD rate, and DCR were 25.8%, 35.5%, and 64.5% (95% CI, 45.4%-80.8%).

At the time of this analysis, the median progression-free survival (PFS) was 5.8 months (95% CI, 2.1-8.7), and the median overall survival (OS) was not reached (95% CI, not calculable [NC]-NC).

Updated findings from cohort B showed that patients achieved a median OS of 17.6 months.3

Safety findings presented at the 2024 ESMO IO Congress demonstrated that grade 3 or higher adverse effects (AEs) occurred in 15.2% of patients (n = 33).2 No serious AEs or AEs leading to death were reported, and AEs led to treatment discontinuation in 9.1% of patients.

The most common any-grade AEs reported in at least 15% of patients comprised fatigue (21.2%), nausea (21.2%), decreased weight (18.2%), hypothyroidism (18.2%), constipation (18.2%), pyrexia (15.2%), arthralgia (15.2%), increased gamma-glutamyl transpeptidase levels (15.2%), diarrhea (15.2%), and anemia (15.2%).

TACTI-003 Overview

The international, open-label study enrolled patients with first-line recurrent or metastatic HNSCC. Patients underwent PD-L1 testing at screening, and those with a CPS of at least 1 were included in cohort A. Cohort B was reserved for patients with a CPS of less than 1.

All patients received eftilagimod alfa at 30 mg once every 2 weeks for the first 6 months of treatment, then once every 3 weeks for up to 2 years. Pembrolizumab was administered at 400 mg once every 6 weeks for up to 2 years.

ORR per RECIST 1.1 criteria served as the trial’s primary end point. Secondary end points included ORR per iRECIST criteria, DOR, safety, PFS, and OS.

References

1. Immutep receives positive feedback from FDA on late-stage clinical development of eftilagimod alfa in head and neck cancer with CPS <1. News release. Immutep. 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. Forster M, Laban S, Metcalf R, et al. TACTI-003 cohort B: eftilagimod alpha (soluble LAG-3) and pembrolizumab in first-line recurrent or metastatic head & neck squamous cell carcinoma with CPS <1. Presented at: 2024 ESMO Immuno-Oncology Congress; December 11-13, 2024; Geneva, Switzerland. Abstract 152P.
3. Immutep’s efti in combination with Keytruda (pembrolizumab) drives strong overall survival in head and neck cancer with CPS <1. News release. Immutep. May 5, 2025. Accessed August 5, 2025. https://www.immutep.com/immuteps-efti-in-combination-with-keytruda-pembrolizumab-drives-strong-overall-survival-in-head-and-neck-cancer-with-cps/