Immutep’s Efti with Radiotherapy & KEYTRUDA® (pembrolizumab) Meets Primary Endpoint in Phase II for Soft Tissue Sarcoma

Rhea-AI Summary

Immutep (NASDAQ: IMMP) has announced positive results from its Phase II EFTISARC-NEO trial, evaluating eftilagimod alfa (efti) in combination with radiotherapy and KEYTRUDA® for resectable soft tissue sarcoma (STS). The trial met its primary endpoint, achieving significantly higher tumor hyalinization/fibrosis rates compared to historical data. The combination therapy demonstrated 50% tumor hyalinization/fibrosis in preliminary analysis, substantially exceeding the prespecified target of 35% and historical radiotherapy-alone data of 15%.

The study, conducted at Poland's national STS reference center, completed enrollment of 40 patients in January 2025. This chemotherapy-free treatment represents a potential breakthrough for STS, an orphan disease with poor prognosis affecting approximately 13,520 new cases in the US in 2025, with an estimated 5,420 deaths.

Positive

• Trial met primary endpoint with 50% tumor hyalinization/fibrosis vs 15% historical data
• Chemotherapy-free combination therapy shows strong anti-cancer efficacy
• Study completed enrollment of 40 patients, exceeding initial analysis of 21 patients
• Results suggest potential improvement in overall survival and recurrence-free survival

Negative

• Detailed results not yet available, pending future medical meeting presentation
• Study limited to resectable soft tissue sarcoma patients only

Insights

Oncology Clinical Trial Expert

Immutep's triple combination therapy shows promising efficacy in soft tissue sarcoma, meeting primary endpoint with significantly better tumor response than historical controls.

The EFTISARC-NEO Phase II trial results represent a significant clinical achievement for Immutep's eftilagimod alfa (efti). The combination of efti with radiotherapy and pembrolizumab demonstrated remarkable efficacy by exceeding the prespecified median of 35% tumor hyalinization/fibrosis versus just 15% for historical radiotherapy data in resectable soft tissue sarcoma (STS).

What's particularly noteworthy is that a preliminary analysis showed a median of 50% tumor hyalinization/fibrosis in 21 patients - substantially surpassing the target threshold. This surrogate endpoint has been associated with improved overall survival and recurrence-free survival in STS patients, making these results clinically meaningful.

The chemotherapy-free approach is especially valuable in STS treatment, where conventional chemotherapy regimens often have limited efficacy and significant toxicity. Efti's mechanism of activating antigen-presenting cells to transform the immunosuppressed tumor microenvironment addresses a fundamental challenge in sarcoma treatment - these tumors are typically immunologically "cold" and resistant to immunotherapy alone.

Soft tissue sarcoma represents a high unmet medical need with approximately 13,520 new cases and 5,420 deaths expected in the US in 2025. As an orphan disease with poor prognosis, any advancement in treatment is significant for this patient population that has seen limited therapeutic innovations. The study's completion of enrollment (40 patients) in January 2025 indicates robust interest in this novel approach.

• Novel combination with efti has met the trial’s primary endpoint of tumour hyalinization/fibrosis in the neoadjuvant setting for patients with resectable soft tissue sarcoma
• Detailed results are planned for presentation at a future medical meeting

 SYDNEY, AUSTRALIA, May 27, 2025 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a late-stage immunotherapy company targeting cancer and autoimmune diseases, today announces the investigator-initiated EFTISARC-NEO Phase II trial evaluating eftilagimod alfa (efti) with radiotherapy plus KEYTRUDA® (pembrolizumab) in the neoadjuvant setting for resectable soft tissue sarcoma (STS) has met its primary endpoint. The novel combination significantly exceeded the study’s prespecified median of 35% tumour hyalinization/fibrosis versus 15% for historical data from radiotherapy alone in patients with resectable soft tissue sarcoma (STS).

Tumour hyalinization/fibrosis is an early surrogate endpoint at the time of surgical resection that has been associated with improved overall survival and recurrence-free survival for STS patients.^1,2 The trial’s investigators at the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, the national reference centre for STS in Poland, plan to present detailed results from the study at a future medical meeting.

Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO and the trial’s principal investigators, said: “It is very encouraging to see the chemotherapy-free combination with efti far exceed the ambitious target we initially set for the trial's primary endpoint in resectable soft tissue sarcoma. These results support our belief that efti's activation of antigen-presenting cells, and in turn a broad adaptive and innate immune response, helps transform the immunosuppressed tumour microenvironment of soft tissue sarcomas leading to strong anti-cancer efficacy. There remains a very high unmet need in this aggressive orphan cancer indication and we look forward to presenting detailed results at a medical meeting later this year.”

As previously announced at the Connective Tissue Oncology Society (CTOS) Annual Meeting in November 2024, the combination therapy demonstrated significant efficacy with a median of 50% tumour hyalinization/fibrosis in a preliminary analysis of 21 patients with resectable STS available for primary endpoint assessment. The EFTISARC-NEO study, which is primarily funded with a grant from the Polish government awarded by the Polish Medical Research Agency program, subsequently completed enrolment of 40 patients in January 2025.

STS is an orphan disease with high unmet medical need and a poor prognosis for patients. The incidence of STS varies in different regions globally. In the United States, the number of new STS cases in 2025 is estimated to be ~13,520 with ~5,420 deaths, according to the American Cancer Society.³

For more information on EFTISARC-NEO, visit clinicaltrials.gov (NCT06128863).

About Eftilagimod Alfa (efti)
Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).

About Immutep
Immutep is a late-stage biotechnology company developing novel immunotherapies for cancer and autoimmune disease. The Company is a pioneer in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and its diversified product portfolio harnesses LAG-3’s ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com.

<sub>1. Schaefer IM et al. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):375-383. doi: 10.1016/j.ijrobp.2017.02.087. Epub 2017 Feb 24. PMID: 28463157.
2. Rao SR et al. Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft-tissue sarcoma. Cancer Med. 2022 Jan;11(1):194-206. doi: 10.1002/cam4.4428. Epub 2021 Nov 27. PMID: 34837341; PMCID: PMC8704179.
3. American Cancer Society statistics: https://www.cancer.org/cancer/types/soft-tissue-sarcoma/about/key-statistics.html</sub>

_{KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.}

Australian Investors/Media:
Catherine Strong, Sodali & Co.
+61 (0)406 759 268; catherine.strong@sodali.com

U.S. Media:
Chris Basta, VP, Investor Relations and Corporate Communications
+1 (631) 318 4000; chris.basta@immutep.com

FAQ

What were the Phase II trial results for Immutep's (IMMP) efti combination therapy in soft tissue sarcoma?

The trial met its primary endpoint, achieving 50% tumor hyalinization/fibrosis, significantly exceeding the target of 35% and historical data of 15% from radiotherapy alone in resectable soft tissue sarcoma patients.

How many patients were enrolled in IMMP's EFTISARC-NEO Phase II trial?

The trial completed enrollment of 40 patients in January 2025, following a preliminary analysis of 21 patients presented at CTOS Annual Meeting in November 2024.

What is the market potential for Immutep's (IMMP) soft tissue sarcoma treatment?

Soft tissue sarcoma represents an orphan disease with high unmet medical need, with approximately 13,520 new cases and 5,420 deaths expected in the US in 2025.

What makes Immutep's (IMMP) efti combination therapy unique for soft tissue sarcoma?

It's a chemotherapy-free combination that activates antigen-presenting cells to transform the immunosuppressed tumor environment, combining efti with radiotherapy and KEYTRUDA®.

When will detailed results of IMMP's Phase II EFTISARC-NEO trial be presented?

The detailed results are planned to be presented at a future medical meeting later in 2025, according to the trial investigators.