Two Posters at ESMO Congress 2025 Highlight Immutep’s Focus on Changing Treatment Landscape in First Line Non-Small Cell Lung Cancer

Rhea-AI Summary

Immutep (NASDAQ: IMMP) reported two posters at ESMO Congress 2025 highlighting clinical activity of eftilagimod alfa (efti) combined with KEYTRUDA and chemotherapy in first-line non-small cell lung cancer (1L NSCLC).

In the investigator-led INSIGHT-003 trial (cut-off 01 Sep 2025, 51 evaluable patients) the combo achieved a 61.7% ORR in patients with TPS <50% versus a 40.8% historical control, with overall ORR by PD-L1: No PD-L1 54.5%, Low 68.0%, High 75.0%; DCRs were 86.4%, 92.0% and 100% respectively. A Trial-in-Progress ePoster described the registrational TACTI-004 Phase III planned to enroll ~756 patients at >150 sites across >25 countries.

Positive

• Efti+KEYTRUDA+chemo achieved 61.7% ORR in TPS <50% (N=47)
• Overall ORR by PD-L1: No 54.5%, Low 68.0%, High 75.0%
• DCRs high across cohorts: 86.4%–100%
• TACTI-004 Phase III to enroll ~756 patients at >150 sites

Negative

• INSIGHT-003 efficacy reported on 51 evaluable patients (limited sample size)
• High PD-L1 subgroup small (TPS ≥50% N=4), limiting subgroup confidence
• Efficacy comparison uses historical control (not randomized head-to-head)

Insights

Clinical Oncologist

Efti added to pembrolizumab+chemo shows higher ORR and DCR across PD-L1 strata, notably 61.7% in TPS <50%.

The combination of efti with pembrolizumab and chemotherapy produced objective response rates and disease control rates in 51 evaluable patients across PD-L1 levels, with ORR of 61.7% in TPS <50% versus a historical control of 40.8%. Reported subgroup ORRs were 54.5% (no PD-L1), 68.0% (low PD-L1), and 75.0% (high PD-L1); DCRs ranged from 86.4% to 100%. These are direct efficacy metrics that clinicians use to judge treatment activity in the first-line setting.

The key dependencies are sample size and maturity: the dataset is 51 evaluable patients with a cut-off of 01 September 2025, and historical-control comparisons can mislead without randomized context. Watch for the registrational TACTI-004 Phase III trial enrolling ~756 patients at over 150 sites in >25 countries and for prespecified primary endpoints and survival readouts in the protocol over the next 12–36 months.

Clinical Development Strategist

INSIGHT-003 efficacy signals support moving to a global Phase III registrational trial, but randomized confirmation is required.

The INSIGHT-003 investigator-initiated data show improved response metrics when adding efti to PD-1 blockade plus chemo, including a notable ORR uplift in the TPS <50% subgroup. The program now includes a Trial-in-Progress TACTI-004 Phase III designed to enroll ~756 patients regardless of PD-L1 status, which aligns the evidence-generation plan with regulatory expectations for a potential label change.

Risks include reliance on historical controls and limited evaluable sample size; the Phase III readout timing and its primary endpoint definitions will determine regulatory and commercial impact. Monitor randomized primary endpoint results, progression-free and overall survival timing, and safety signals during the next 12–48 months as the definitive tests of whether these earlier response improvements translate into regulatory and practice change.

• Novel combination of efti with KEYTRUDA^® and chemotherapy generates strong response rates across all PD-L1 expression levels in first line non-small cell lung cancer (1L NSCLC) including 61.7% ORR in low & no PD-L1 (TPS <50%), well above 40.8% from historical controls
  
  
• Efti’s ability to expand responders & enhance efficacy with PD-1 inhibitors, the best selling class of drugs in oncology, holds great promise to change 1L NSCLC treatment paradigm
  
  

SYDNEY, AUSTRALIA, Oct. 20, 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 two poster presentations at the European Society for Medical Oncology (ESMO) Congress 2025 highlight the Company’s focus on changing the treatment paradigm in first line non-small cell lung cancer (1L NSCLC).

Promising data from the investigator-initiated INSIGHT-003 trial with a cut-off date of 01 September 2025 were detailed in a poster presented by Dr. med. Akin Atmaca, Head of the Thoracic Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, Germany. In this multi-centre study, the novel combination of eftilagimod alfa (efti) with KEYTRUDA^® (pembrolizumab) and chemotherapy (carboplatin/pemetrexed) has generated strong objective response rates (ORR) and disease control rates (DCR) in 51 evaluable patients with advanced or metastatic non-squamous 1L NSCLC across all PD-L1 expression levels (see table below).

Notably, the ORR and DCR reported in INSIGHT-003 outperforms historical controls irrespective of PD-L1 levels. This is particularly important for patients with low and no PD-L1 (TPS <50%), who represent over two-thirds of the 1L NSCLC patient population and for whom PD-(L)1 inhibitors typically perform suboptimally. In patients with TPS <50% (N=47), the combination with efti has achieved a strong and improved 61.7% ORR (with an additional partial response since 06 May 2025 data cutoff) as compared to historical control of 40.8%.^1,2

Efti+KEYTRUDA+Chemo Generates High ORR & DCR Across All PD-L1 Levels (RECIST 1.1)

	No PD-L1 (TPS <1%, N=22)	Low PD-L1 (TPS 1-49%, N=25)	High PD-L1 (TPS ≥50%, N=4)
ORR, %	54.5	68.0	75.0
DCR, %	86.4	92.0	100

Dr. Atmaca, Head of Thoracic Oncology at Krankenhaus Nordwest, stated: “While the introduction of PD-(L)1 inhibitors, both alone and with chemotherapy, has revolutionised 1L NSCLC treatment, their limited effectiveness in cases with minimal or absent PD-L1 expression highlights the ongoing need for innovative strategies that better harness the immune system against cancer. The favourable safety results and strong clinical responses seen when adding efti, a novel immunotherapy bridging adaptive and innate immunity, to KEYTRUDA and chemotherapy are highly promising and could benefit NSCLC patients irrespective of their PD-L1 status.”

Marc Voigt, CEO of Immutep, stated: “We are increasingly confident that efti can set a new standard of care as first line treatment for non-small cell lung cancer patients through our pivotal TACTI-004 Phase III trial, supported by strong data from multiple clinical trials evaluating efti in lung cancer including INSIGHT-003. Efti has safely and consistently delivered impressive improvements in response rates and progression free survival compared to KEYTRUDA alone or with chemotherapy, and encouragingly these have translated into compelling overall survival. Notably, the data is especially promising in patients with PD-L1 expression under 50%, who have a high unmet need and represent more than two-thirds of the 1L NSCLC patient population.”

Further to the strong efficacy data from INSIGHT-003, the combination with efti continues to have a favourable safety profile.

Additionally, a Trial in Progress ePoster for the TACTI-004 Phase III was presented at ESMO Congress 2025. This registrational trial is evaluating the same immunotherapy/chemotherapy combination used in INSIGHT-003. This global study will enrol approximately 756 patients with advanced/metastatic 1L NSCLC regardless of PD-L1 expression (Tumour Proportion Score or TPS of 0-100%) with non-squamous or squamous tumours at over 150 clinical sites in over 25 countries.

The poster for INSIGHT-003 and the Trial in Progress ePoster for TACTI-004 can be found at the Posters & Publications section of Immutep’s website.

About Eftilagimod Alfa (Efti)
Efti is a novel immunotherapy that directly activates antigen-presenting cells or APCs (e.g. dendritic cells, monocytes) via the MHC Class II pathway to fight cancer. As an MHC Class II agonist, its activation of APCs engages the adaptive and innate immune system to initiate a broad anti-cancer immune response. This includes priming and activating cytotoxic T cells as well as generating important co-stimulatory signals & cytokines that further boost the immune system’s ability to combat cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC) in a pivotal Phase III trial called TACTI-004 (KEYNOTE-F91), as well as head and neck squamous cell carcinoma (HNSCC), soft tissue sarcoma, and breast cancer. Its favourable safety profile enables various combinations like with anti-PD-[L]1 immunotherapy, radiotherapy, 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.

1. Shirish Gadgeel et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer. JCO 38, 1505-1517(2020). DOI:10.1200/JCO.19.03136
2. Immutep’s Efti with KEYTRUDA® (pembrolizumab) & Chemotherapy Achieves High Response Rates in First-Line Non-Small Cell Lung Cancer - May 2025 press release

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

Australian Investors/Media:
Eleanor Pearson, Sodali & Co.
+61 2 9066 4071; eleanor.pearson@sodali.com

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

FAQ

What ORR did Immutep (IMMP) report for efti+KEYTRUDA+chemo in 1L NSCLC at ESMO 2025?

INSIGHT-003 reported ORR by PD-L1: No PD-L1 54.5%, Low 68.0%, High 75.0%, and 61.7% ORR in patients with TPS <50%.

How does the 61.7% ORR for IMMP's efti combo compare to historical controls?

The 61.7% ORR in TPS <50% compares to a 40.8% historical control cited in the presentation.

What is the size and scope of Immutep's registrational TACTI-004 Phase III trial (IMMP)?

TACTI-004 is planned to enroll approximately 756 patients at over 150 clinical sites in more than 25 countries, regardless of PD-L1 score.

Were there safety concerns reported for efti combined with KEYTRUDA and chemotherapy?

The posters reported a favourable safety profile for the efti combination without specifying major safety signals.

When was the INSIGHT-003 data cut-off cited for Immutep's ESMO 2025 posters?

The INSIGHT-003 data cut-off cited was 01 September 2025.