Eftilagimod Alpha/Pembrolizumab Elicits Encouraging Responses in HNSCC


The phase 2b findings support the capability of eftilagimod alpha to enhance the potential of immune checkpoint inhibitors in metastatic HNSCC.

Investigators continue to perform data collection, cleaning, and analysis for the TACTI-003 trial (NCT04811027). Reports of ORR data from cohort A and cohort B are anticipated in the first half of 2024.

Investigators continue to perform data collection, cleaning, and analysis for the TACTI-003 trial (NCT04811027). Reports of ORR data from cohort A and cohort B are anticipated in the first half of 2024.

Combining eftilagimod alpha (efti) with pembrolizumab (Keytruda) as frontline therapy demonstrated preliminary responses and disease control in a small cohort of patients with recurrent or metastatic PD-L1–negative head and neck squamous cell carcinoma (HNSCC), according to a press release on topline results from cohort B of the phase 2b TACTI-003/KEYNOTE-PNC-34 trial (NCT04811027).1

The combination produced an overall response rate (ORR) of 26.9% in 26 evaluable patients with a PD-L1 combined positive score of less than 1. Additionally, the disease control rate (DCR) in this cohort was 57.7%.

Developers believe these findings support the ability of efti to activate antigen-presenting cells, thereby boosting the potential efficacy of immune checkpoint inhibitors. Specifically, efti is believed to influence the expansion of memory cytotoxic T cells that anti–PD-1 or anti–PD-L1 agents can act upon.

Investigators continue to perform data collection, cleaning, and analysis for the TACTI-003 trial. Reports of ORR data from cohort A and cohort B are anticipated in the first half of 2024.

“These preliminary topline results in the first line setting for patients with head and neck squamous cell cancers that do not express PD-L1 are encouraging. [HNSCCs] are a heterogenous disease that represents a high unmet medical need regardless of PD-L1 expression,” trial investigator Martin Forster, MD, PhD, of the University College London Cancer Institute and University College London Hospital NHS Foundation, said in the press release.1 “The ability of efti to work with [pembrolizumab] to potentially improve patients’ clinical responses and expand patient populations that respond to the latter, without using chemotherapy, is promising.”

In cohort B of the TACTI-003 trial, investigators are assessing efti plus pembrolizumab in patients whose tumors are PD-L1 negative. In cohort A, investigators are evaluating efti plus pembrolizumab compared with pembrolizumab alone in those with PD-L1–positive tumors.

Patients received efti at 30 mg every 2 weeks for the first 4 cycles followed by every 3 weeks thereafter for a maximum of 18 cycles.2 Additionally, investigators administered pembrolizumab at 400 mg every 6 weeks for up to 18 cycles.

The trial’s primary end point was ORR based on RECIST v1.1 criteria. Secondary end points included overall survival, progression-free survival, duration of response, DCR, adverse effects, and quality of life.

Patients 18 years and older with histologically or cytologically confirmed recurrent disease not amenable to curative local or systemic treatment and metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx determined to be incurable with local therapies were eligible for enrollment on the trial. Other eligibility criteria included having available tissue for PD-L1 biomarker analysis, availability of tissue for evaluation of human papillomavirus status for oropharyngeal cancer, and an ECOG performance status of 0 or 1.

Those with disease suitable for local therapy given with curative intent or prior treatment with 1 or more systemic treatments for recurrent and/or metastatic disease were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had progressive disease within 6 months of completing curatively intended systemic therapy for locally or locoregionally advanced HNSCC; prior treatment with agents targeting PD-1, PD-L1, PD-L2, CD137, or CTLA-4; or known central nervous system metastases and/or carcinomatous meningitis. Receiving continuous systemic therapy with corticosteroids or other immunosuppressive agents within a week of beginning study treatment was also grounds for exclusion from the trial.

The FDA previously granted fast track designation to efti as a first-line treatment for recurrent or metastatic HNSCC in April 2021.3 Supporting findings for the fast track designation came from the phase 2 TACTI-002 trial (NCT03625323).


  1. Immutep announces positive preliminary topline results from TACTI-003 cohort B. News release. Immutep Limited. April 24, 2024. Accessed April 25, 2024. https://tinyurl.com/4zhfa6p4
  2. Combination study with eftilagimod alpha (a soluble LAG-3 fusion protein) and pembrolizumab in patients with recurrent or metastatic HNSCC (TACTI-003). ClinicalTrials.gov. Accessed April 25, 2024. https://tinyurl.com/46kdym9k
  3. 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 25, 2024. https://tinyurl.com/4d2vrubz
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