An Independent Data Monitoring Committee (IDMC) has recommended the termination of the phase 3 TACTI-004 trial (NCT06726265) evaluating frontline eftilagimod alfa in patients with non–small cell lung cancer (NSCLC), following a planned interim futility analysis of the available safety and efficacy data.1
In accordance with IDMC’s recommendation, enrollment in the study will stop, and the sponsor will implement an orderly wind-down, allowing for patient follow-up and site close-outs.
“We are very disappointed and surprised with the outcome of the futility analysis, in light of efti’s performance in every other clinical trial” Marc Voigt, chief executive officer of Immutep Limited, stated in a news release.1 “We would like to thank the patients, investigators, and clinical teams who contributed to this important study. We are currently conducting a comprehensive review of the available data to better understand the results and determine the appropriate next steps for the program.”
Phase 3 TACTI-004 Trial Halted After Interim Futility Analysis
- An IDMC recommended terminating the TACTI-004 study after a planned interim futility analysis evaluating eftilagimod alfa plus pembrolizumab and chemotherapy in patients with advanced NSCLC.
- The phase 3 program followed encouraging results from the phase 2 TACTI-002 trial, where the combination produced response rates exceeding 38% and led to FDA fast track designation.
- TACTI-004 was designed to enroll approximately 756 patients with metastatic NSCLC without EGFR, ALK, or ROS1 alterations to assess improvements in PFS and OS with the addition of the MHC class II agonist to standard chemoimmunotherapy.
What is eftilagimod alfa?
Eftilagimod alfa is a novel immunotherapy agonist that engages the adaptive and innate immune system by activating antigen-presenting cells through the MHC Class II pathway. The resulting anticancer immune response includes priming and activating cytotoxic T cells, as well as generating co–stimulatory signals and cytokines that amplify the immune system’s ability to attack the cancer.
In October 2022, the FDA granted a fast track designation to the agent for use in combination with pembrolizumab as frontline therapy for patients with NSCLC.2
The designation was based on data from the phase 2 TACTI-002 trial (NCT03625323), which showed an overall response rate (ORR) of 38.6% (95% CI, 29.6%-48.2%) by iRECIST (immune-related Response Evaluation Criteria in Solid Tumors) criteria, per the local investigator, in patients with advanced or metastatic NSCLC (n = 114) treated with the combination. Among evaluable patients treated with the combination (n = 103), the iRECIST ORR per local read was 42.7% (95% CI, 33.0%-52.9%).3
What was the design of the TACTI-004 trial?
TACTI-004 was a global, randomized, double-blind, placebo-controlled phase 3 trial evaluating the addition of eftilagimod alfa to first-line pembrolizumab (Keytruda) and histology-based chemotherapy for patients with advanced or metastatic squamous or nonsquamous NSCLC with no EGFR, ALK, or ROS1 alterations.4
Patients with squamous histology received 4 cycles of carboplatin at area under the curve (AUC) 5 or 6 plus 175 mg/m2 or 200 mg/m2 of paclitaxel every 3 weeks. Those with nonsquamous histology received 75 mg/m2 of cisplatin or carboplatin at AUC 5 or 6 plus 500 mg/m2 of pemetrexed every 3 weeks for 4 cycles, followed by pemetrexed maintenance.
In the investigational arm, patients also received 30 mg of eftilagimod alfa subcutaneously every 2 weeks for the first 6 months, then every 3 weeks thereafter, plus 200 mg of intravenous pembrolizumab every 3 weeks for a total of 2 years.
The trial was expected to enroll approximately 756 patients regardless of PD-L1 expression at over 150 clinical sites in more than 25 countries. Eligible patients 18 years or older had to have received a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC that was not amenable to curative treatment or targeted therapy. Prior exposure to systemic therapy in the advanced or metastatic setting was prohibited, and PD-L1 testing results were mandated from a central lab using the FDA-approved 22C3 pharmDx assay.
Patients were randomly assigned 1:1 to receive eftilagimod alfa plus pembrolizumab and chemotherapy or pembrolizumab plus chemotherapy and placebo.
The study’s dual primary end points were progression-free survival and overall survival. Key secondary end points included ORR, time to response, duration of response, time to second progression, and safety.
References
- TACTI-004 phase III study in first-line NSCLC to be discontinued following futility analysis. News release. Immutep Limited. March 13, 2026. Accessed March 13, 2026. https://www.immutep.com/11560-2/
- Immutep receives FDA fast track designation for LAG-3 therapeutic eftilagimod alpha for first-line non–small cell lung cancer. News release. Immutep Limited. October 4, 2022. Accessed March 13, 2026. https://www.immutep.com/dw/uploads/2025/05/IMM20-20Fast20Track20Granted20by20US20FDA20for20Efti20in201st20Line20NSCLC20-2004Oct2022.pdf
- Felip E, Majem M, Doger B, et al. A phase II study (TACTI-002) in first-line metastatic non–small cell lung carcinoma investigating eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab: updated results from a PD-L1 unselected population. J Clin Oncol. 2022;40(suppl 16):9003. doi:10.1200/JCO.2022.40.16_suppl.9003
- 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. Updated February 27, 2026. Accessed March 13, 2026. https://clinicaltrials.gov/study/NCT06726265
