FDA Grants Fast Track Designation to 1L Eftilagimod Alpha for Recurrent or Metastatic HNSCC


A Fast Track designation was granted by the FDA to the soluble LAG-3 protein, eftilagimod alpha for the frontline treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma.

FDA update

A Fast Track designation was granted by the FDA to the soluble LAG-3 protein, eftilagimod alpha (IMP321) for the frontline treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to a press release from the developer, Immutep Limited.1

The agent has the potential to address an unmet medical need in the recurrent or metastatic HNSCC patient population based on evidence of a positive risk-benefit ratio shown in part C of the phase 3 TACTI-002 trial (NCT03625323) in patients treated with eftilagimod alpha in combination with pembrolizumab (Keytruda), in the second-line setting.

Following a Simon's 2-stage design, the primary end point of the ongoing study is overall response rate (ORR), and the secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), pharmacodynamics, and immunogenicity. Patients are eligible to join the HNSCC cohort given they have histologically or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or have metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is not treatable with local therapies after failure of prior platinum-based therapy. Patients are required to have an ECOG performance status of 0 or 1, and a life expectancy of more than 3 months.

The investigational agent was administered to patients as 30 mg by subcutaneous injection every 2 weeks for 8 cycles and then every 3 weeks for 9 cycles in combination with pembrolizumab which was administered at 200 mg via intravenous infusion every 3 weeks for up to 2 years. The study population was comprised of 88 patients, which also included individuals with non–small cell lung cancer. The HNSCC cohort included 28 patients and 18 were evaluable for efficacy and safety. The overall population had a median age of 67 years (range, 53-84 years). The majority of the study population was male (70%), and the ECOG performance status was 0 in 42% of patients and 1 in the remaining 58%.2

Patients with HNSCC were followed for a median of 9.5 months on treatment with eftilagimod alpha and pembrolizumab. The ORR observed with the combination was 38.9% (95% CI, 17.3%-64.3%), which included complete responses in 11.1% for a DCR of 50%. In patients with HNSCC and low PD-L1, the response rate was 25.0%.

Survival data showed a median PFS of 4.26 months (95% CI, 1.48 months to no evaluable) in the HNSCC cohort. The OS rates at 9 months and 12 months were 67% and 60%, respectively, and the 15-month OS rate was not reached.

Second-line treatment with eftilagimod alpha and pembrolizumab in patients HNSCC also showed a mean with Cmax at7 ng/ml reached ≤ 24h, demonstrating consistency with the prior PK data for eftilagimod alpha.

As of data cutoff, 7 patients with HNSCC were still on treatment for 6 months or more.

In terms of safety, the combination led to treatment-emergent adverse events in 15% of the overall study population. The most common TEAEs were asthenia (28%), cough (27%), decreased appetite (22%), dyspnea (21%), fatigue (18%), and diarrhea (15%). There were 3 treatment discontinuations as a result of AEs.

Conclusions drawn from these interim data were that eftilagimod alpha can lead to deep and durable responses in patients with HNSCC even in patients with low PD-L1 expression who do not typically respond to therapy. In addition, the combination of eftilagimod alpha and pembrolizumab is well-tolerated with no new safety signals shown. Based on the results of TACTI-002 trial, a phase 3 trial (TACTI-003; NCT04811027) exploring the combination as frontline treatment of HNSCC.1,2

Eftilagimod alpha binds to a subset of MHC class II molecules to control antigen-presenting cell activation as well as CD8 T-cell activation. This mechanism of action may lead to stronger anti-tumor responses compared with the standard-of-care pembrolizumab.2


1. IMMUTEP achieves Fast Track designation from us FDA for efti, a soluble lag-3 protein, in first line recurrent/metastatic head & neck cancer. News release. Immutep Limited. April 8, 2021. Accessed April 8, 2021. https://bit.ly/3rYtQpt

2. Krebs M, Majem M, Felip E, et al. 790 A phase II study (TACTI-002) of eftilagimod alpha (a soluble LAG-3 protein) with pembrolizumab in PD-L1 unselected patients with metastatic non-small cell lung (NSCLC) or head and neck carcinoma (HNSCC). Journal for ImmunoTherapy of Cancer. 2020;8 (suppl 3). doi: 10.1136/jitc-2020-SITC2020.0790

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