Investigators to Discontinue Trial of Eftilagimod Alfa in Frontline NSCLC

Investigators will discontinue their assessment of eftilagimod alfa (efti) in combination with pembrolizumab (Keytruda) and chemotherapy among patients with first-line non–small cell lung cancer (NSCLC) as part of the phase 3 TACTI-004 trial (NCT06726265), according to a press release from the developer, Immutep Limited.¹

Following an evaluation of available efficacy and safety data, an independent data monitoring committee (IDMC) recommended that investigators terminate the trial for futility. Based on the IDMC’s feedback, investigators will halt enrollment for the trial. Additionally, developers plan to facilitate an orderly wind down of the study encompassing sufficient patient follow-up and site close out in observance of ethical and regulatory considerations.

“We are very disappointed and surprised with the outcome of the futility analysis, in light of efti’s performance in every other clinical trial. We would like to thank the patients, investigators, and clinical teams who contributed to this important study,” Marc Voigt, chief executive officer at Immutep, stated in the press release.¹ “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.”

Investigators of the double-blind phase 3 TACTI-004 trial assessed efti plus pembrolizumab and chemotherapy among patients with advanced or metastatic NSCLC harboring no EGFR, ALK, or ROS1 alterations. The study was intended to include an approximate population of 756 patients with any PD-L1 expression and squamous or nonsquamous histology across 150 clinical sites in more than 25 countries.

Patients were randomly assigned to receive 30 mg of efti every 2 weeks subcutaneously for 6 months followed by every 3 weeks for a maximum of 24 months or matched placebo plus pembrolizumab and chemotherapy.² Investigators also administered pembrolizumab at 200 mg intravenously every 3 weeks for a maximum of 24 weeks. Chemotherapy consisted of carboplatin/paclitaxel or cisplatin or carboplatin plus pemetrexed.

The trial’s primary end points were overall survival and progression-free survival (PFS) per RECIST v1.1 criteria. Secondary end points included objective response rate, frequency of adverse effects (AEs), severity of AEs, time to response, duration of response, and PFS on the next line of therapy.

Patients 18 years and older with histologically or cytologically confirmed advanced or metastatic NSCLC not amenable to curative therapy, evaluable PD-L1 biomarker results per central laboratory assessment, and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Other eligibility criteria included having an expected survival of more than 3 months and adequate organ function.

Those with prior radiotherapy within 2 weeks of beginning study treatment; prior treatment with anti–PD-L1, anti–PD-1, or anti–PD-L2 agents; prior high-dose chemotherapy requiring hematopoietic stem cell rescue; known active central nervous system metastases and/or carcinomatous meningitis; or evidence of severe or uncontrolled cardiac disease within 6 months of initiating study treatment were ineligible for enrollment on the trial. Patients were also ineligible for study entry if they had a history of allogeneic tissue or solid organ transplant or a known additional malignancy that was progressing or required active therapy within the past 3 years.

Developers designed efti as an agent that directly activates antigen-presenting cells (APCs) through the MHC Class II pathway. The agent’s activation of APCs may facilitate priming and activation of cytotoxic T cells while producing critical co-stimulatory signals and cytokines that empower the immune system to target cancer.

Based on a Type C meeting, the FDA previously gave positive feedback to the trial design of TACTI-004 in July 2024.³

References

1. TACTI-004 phase III study in first line NSCLC to be discontinued following futility analysis. News release. Immutep Limited. March 13, 2026. Accessed March 16, 2026. https://tinyurl.com/mr3a7bf7
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. Updated February 27, 2026. Accessed March 16, 2026. https://tinyurl.com/52ed58um
3. Immutep announces successful meeting with FDA on phase III design in non-small cell lung cancer. News release. Immutep Limited. July 22, 2024. Accessed March 16, 2026. https://tinyurl.com/mw43epzc