FDA Supports Further Evaluation of Eftilagimod Alpha in NSCLC


The FDA has provided positive feedback in establishing further research for eftilagimod alpha in frontline non–small cell lung cancer.

Wade T. Iams, MD

Wade T. Iams, MD

The FDA is supporting a registrational trial to evaluate eftilagimod alpha (efti; IMP321), a first-in-class soluble LAG-3 protein and MHC class II agonist, for the treatment of first-line non–small cell lung cancer (NSCLC).1

In the trial, investigators will assess efti combined with an anti-PD-1 therapy. The study follows promising data from the phase 2 TACTI-002 trial (NCT03625323) where in part A, 114 patients with first-line NSCLC patients who had any level of PD-L1 expression were evaluated.

Findings revealed that deep and durable responses were observed when these patients were treated with the immunotherapy combination of pembrolizumab (Keytruda) and efti in patients with advanced NSCLC.2

“Efti is a soluble LAG3 agonist that stimulates immune activation at the antigen presenting cell level, upstream of the site of activity of currently available immune checkpoint inhibitors which function at the level of the tumor and immune cell interaction,” said Wade T. Iams, MD, assistant professor of medicine in the Division of Hematology and Oncology at Vanderbilt University Medical Center in Nashville, Tennessee, told Targeted OncologyTM. “We need more patients with NSCLC treated with efti and longer follow-up of these patients to best evaluate the ability of efti to improve outcomes compared to our currently available standard of care immunotherapies.”

Efti works by binding to a major histocompatibility complex on antigen presenting cells.1 This leads to CD8 T-cell activation in patients, along with the activation and proliferation of CD4+ helper T cells, dendritic cells, NK cells, and monocytes. Further, efti upregulates the expression of key biological molecules, including IFN-ƴ and CXCL10, which boost the immune system’s ability to fight cancer.

Numerous clinical trials are evaluating efti for use in patients with NSCLC, head and neck squamous cell carcinoma, and hormone receptor-positive/HER2-negative metastatic breast cancer as its safety profile is favorable and allows it to be potentially beneficial in various combinations, including with anti-PD-(L)1 immunotherapy and/or chemotherapy.

Previously in October 2022, the FDA granted a fast track designation to efti in combination with pembrolizumab for the frontline treatment for patients with stage IIIB/IV NSCLC with a PD-L1 tumor proportion score of at least 1%, based on earlier findings from the TACTI-002 trial.2

“In light of our compelling clinical data that efti has generated in combination with anti-PD-1 therapy, this meeting with the FDA is a critical step in our late-stage development process for 1st line non–small cell lung cancer. We are thankful for the positive feedback as we continue moving forward with our unique immuno-oncology approach for the many cancer patients impacted by this difficult disease,” Marc Voigt, chief executive officer of Immutep, said in the press release.

In the phase 2 TACTI-002 trial, patients treated with the first-line combination in the intent-to-treat population (ITT) had a 40.4% (95% CI, 31.3%-50.0%) overall response rate (ORR) by immune RECIST criteria, and the ORR was made up of a 0.9% complete response (CR) rate and a 39.5% partial response (PR) rate. A total of 32.5% of patients had stable disease (SD), 15.8% of patients had progressive disease (PD), and 11.4% of patients were not evaluable (NE). In this population, the median duration of response (DOR) was 21.6 months (95% CI, 17.3-30.0).

The ORR in the ITT population was 38.6% (95% CI, 29.6%-48.2%) and included a 0.9% CR rate and a 37.8% PR rate when assessed by RECIST v1.1 criteria. Additionally, the SD rate was 32.5%, PD rate was 17.5%, and 11.4% of patients were NE, respectively.

Regarding safety, the safety profile was consistent with prior reports on the combination. Grade 3 or greater adverse effects (AEs) were observed in 12.3% of patients. Serious AEs occurred in 10.5% of patients, and AEs that led to treatment discontinuation occurred in 9.6% of patients. Additionally, AEs that led to death occurred in 3 patients.

Of any grade by preferred term, AEs included pruritus (20.2%), asthenia (19.3%), rash (13.2%), diarrhea (10.6%), and fatigue (10.5%). Grade 3 diarrhea and fatigue were reported in 1 patient each.

“In patients with NSCLC, achieving durable disease control for a larger group of patients with less [adverse] effects than current treatment regimens is the major unmet need,” added Thomas.

1. Immutep receives positive feedback from FDA on late-stage clinical development of eftilagimod alpha in non-small cell lung cancer. News release. Immutep Limited. May 16, 2023. Accessed May 17, 2023. https://yhoo.it/3OiGTRJ
2. Iams W, Felip E, Majern M, et al. Combining the antigen-presenting cell activator eftilagimod alpha (soluble LAG-3) and pembrolizumab: efficacy results from the 1st line non-small cell lung cancer cohort of TACTI-002 (phase II). Abstract presented at: Society for Immunotherapy of Cancer 37th Annual Meeting & Pre-Conference Programs; November 8-12, 2022; Boston, MA. Abstract 1470.
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