Immutep will focus eftilagimod alfa development on PD-L1-negative HNSCC and neoadjuvant soft tissue sarcoma after TACTI-004 findings.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Immutep plans to restart registration-directed development of eftilagimod alfa in two settings after a root cause analysis linked the failed TACTI-004 study to analytical differences between 200 L and 2,000 L manufacturing scales.
Manufacturing findings reshape efti development
Immutep is narrowing the clinical development strategy for eftilagimod alfa (efti) to head and neck squamous cell carcinoma (HNSCC) with PD-L1 Combined Positive Score (CPS) <1 and the neoadjuvant treatment of soft tissue sarcoma (STS).
The decision follows the early discontinuation of the Phase II/III TACTI-004 trial and an ongoing investigation into why efti produced a markedly different immune activation profile and clinical outcome than in earlier studies.
The root cause analysis has identified subtle structural and analytical differences between efti manufactured at 200 L and 2,000 L scales, including differences in N-glycan structure. Immutep considers these findings potentially relevant to TACTI-004, which used only the 2,000 L-scale product.
The company said its analysis to date has not identified clinical or trial-execution factors that adequately explain the unexpected TACTI-004 outcome.
New 200 L manufacturing run planned
Immutep has contracted a new manufacturing run of efti at the 200 L scale. Ten GMP batches had previously been produced at this scale and supplied successful Phase I and Phase II studies, including TACTI-mel, TACTI-002 and INSIGHT-003.
The manufacturing distinction is important because the company intends to use the new 200 L product as it prepares the next generation of clinical studies. Further investigation of product-batch differences remains underway.
Focus shifts to two registration-directed settings
In HNSCC, Immutep plans to concentrate on patients with CPS <1, a population with substantial unmet need and limited approved treatment options. The strategy is supported by clinical efficacy data, including mature overall survival results, alongside constructive interactions with the U.S. Food and Drug Administration (FDA).
Efti has received FDA Fast Track designation in first-line HNSCC, strengthening the regulatory rationale for continued development.
The second focus is neoadjuvant STS, where Phase II data showed a positive outcome and met the study’s primary endpoint. The FDA granted efti Orphan Drug Designation for STS in April 2026.
Efti activates antigen-presenting cells
Efti is an immunotherapy that activates antigen-presenting cells (APCs), including dendritic cells and monocytes, through the MHC class II pathway. This mechanism promotes both innate and adaptive immune responses, including activation and priming of cytotoxic T cells and induction of co-stimulatory signals and cytokines.
Its safety profile has supported evaluation in combination with anti-PD-1/PD-L1 therapies, radiotherapy and chemotherapy.
The broader LAG-3 pipeline also remains active, with development of IMP761, an agonist anti-LAG-3 antibody for autoimmune disease, continuing under previously disclosed plans.
Clinical restart targeted for 2H 2027
Preparations for the next clinical trials have begun, with study initiation targeted for the second half of calendar year 2027. The timeline remains dependent on final trial designs, further regulatory discussions, manufacturing schedules, potential partnering and available resources.
CEO Marc Voigt said the company sees a scientifically and clinically supported path for efti based on the totality of clinical and translational evidence, while acknowledging the significance of TACTI-004. Immutep’s licensing partner, Dr. Reddy’s Laboratories, supports the revised approach, and the company is also holding preliminary discussions with other potential partners.
The immediate priority is therefore not broad clinical expansion, but resolving the manufacturing questions and advancing efti selectively into the indications where prior efficacy, biological rationale, regulatory positioning and unmet need provide the strongest development case.
Reference
Immutep Outlines Focused Development Strategy for Eftilagimod Alfa (“efti”), Immutep, 11 September 2026
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.