TACTI-004 Trial Studying Eftilagimod Alfa With Pembrolizumab in Advanced NSCLC to Begin Evaluation

The double-blinded, randomized phase 3 trial, TACTI-004 (KEYNOTE-F91; NCT06726265), which will assess the use of eftilagimod alfa (efti; Immutep Limited) in combination with pembrolizumab (Keytruda; Merck) and chemotherapy as first-line treatment for advanced or metastatic non–small cell lung cancer (NSCLC), has enrolled and will randomly assign 170 patients for evaluation, according to a news release.

Investigators noted that this is an important milestone, as it surpasses the number of participants needed to conduct the futility analysis.^1,2

“We are very pleased with the pace of enrollment in our pivotal phase 3 trial that we believe has the potential to change the treatment landscape in NSCLC, one of the largest indications in oncology with over 2 million diagnoses annually worldwide. The trial remains on track for key milestones ahead including futility analysis in early 2026,” Marc Voigt, CEO of Immutep, said in a news release.¹

TACTI-004 is a phase 3 trial evaluating efti in combination with pembrolizumab and chemotherapy as first-line therapy for patients with advanced or metastatic NSCLC with no EGFR, ALK, or ROS1 genomic tumor aberrations. The trial aims to enroll about 756 patients regardless of PD-L1 expression and with nonsquamous or squamous tumors at over 150 clinical sites in over 25 countries.

Patients will be randomly assigned 1:1 to receive either efti in combination with pembrolizumab and chemotherapy in the treatment arm, or pembrolizumab in combination with chemotherapy and placebo in the control arm. The study’s dual primary end points are progression-free survival (PFS) and overall survival (OS).^1,2

The TACTI-004 study follows positive efficacy and safety results from 2 prior trials, TACTI-002 (NCT03625323)³ and INSIGHT-003 (NCT03252938)⁴, both of which tested efti alongside pembrolizumab as a first-line treatment in NSCLC. Over 165 patients were enrolled across both trials, and the results demonstrated that efti enhances anti–PD-1 therapy regardless of PD-L1 expression levels in patients. The novel combination of these 2 immunotherapies has led to high response rates and strong PFS, which translate into significantly improved OS, addressing a high unmet need for these patients.^1,2

Efti is a novel immunotherapy that directly activates antigen-presenting cells (APCs)—such as dendritic cells and monocytes—via the MHC class II pathway to fight cancer. As an MHC class II agonist, its activation of APCs initiates a broad anticancer immune response, including priming and activating cytotoxic T cells and generating important costimulatory signals and cytokines that further boost the immune system’s ability to combat cancer.

Currently, efti is under evaluation for a variety of solid tumors, including NSCLC, head and neck squamous cell carcinoma (HNSCC), soft tissue sarcoma, and breast cancer. In trials, it has demonstrated a favorable safety profile that allows for its use with various agents, including anti–PD-L1 immunotherapy, radiotherapy, and/or chemotherapy. The FDA has granted efti a fast track designation in first-line HNSCC and in first-line NSCLC.¹

“Our engagement with the principal investigators and physicians in the lung cancer community at medical conferences throughout the year, including [World Conference on Lung Cancer] 2025, has consistently resulted in constructive feedback. Their favorable assessments of the trial design and of efti as an innovative immunotherapy—capable of safely increasing response rates and improving efficacy in NSCLC patients regardless of PD-L1 expression—provide a strong basis for ongoing positive enrollment trends,” Stephan Winckels, MD, PhD, chief medical officer of Immutep, said in the news release.¹

REFERENCES

1. Immutep. Immutep Announces Update for TACTI-004 (KEYNOTE-F91) Phase III Trial in First Line Non-Small Cell Lung Cancer. News release. October 9, 2025. Accessed October 13, 2025. https://www.immutep.com/immutep-announces-update-for-tacti-004-keynote-f91phase-iii-trial-in-first-line-non-small-cell-lung-cancer/

2. Study of Eftilagimod Alfa (Efti) in Combination With Pembrolizumab and Chemotherapy Versus Placebo in Combination With Pembrolizumab and Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) (TACTI-004). ClinicalTrials.gov identifier: NCT06726265. Updated October 1, 2025. Accessed October 13, 2025. https://www.clinicaltrials.gov/study/NCT06726265

3. Combination Study With Soluble LAG-3 Fusion Protein Eftilagimod Alpha (IMP321) and Pembrolizumab in Patients With Previously Untreated Unresectable or Metastatic NSCLC, or Recurrent PD-X Refractory NSCLC or With Recurrent or Metastatic HNSCC (TACTI-002). ClincialTrials.gov identifier: NCT03625323. Updated December 18, 2024. Accessed October 13, 2025. https://clinicaltrials.gov/study/NCT03625323

4. Feasibility and Safety of IMP321 (Eftilagimod Alpha) for Advanced Stage Solid Tumors (INSIGHT). ClinicalTrials.gov identifier: NCT03252938. Updated February 13, 2025. Accessed October 13, 2025. https://clinicaltrials.gov/study/NCT03252938