Immutep’s Efti with KEYTRUDA® (pembrolizumab) & Chemotherapy Achieves High Response Rates in First-Line Non-Small Cell Lung Cancer

Rhea-AI Summary

Immutep (NASDAQ: IMMP) has reported impressive results from its INSIGHT-003 trial evaluating eftilagimod alpha (efti) in combination with KEYTRUDA® and chemotherapy for first-line non-small cell lung cancer (NSCLC). The treatment achieved a 60.8% overall response rate and 90.2% disease control rate across all PD-L1 expression levels. Notably, ~92% of evaluable patients had PD-L1 TPS <50%, including 43% with PD-L1 below 1%. The combination showed significant improvements compared to historical controls, particularly in patients with lower PD-L1 expression: 75.0% vs 62.1% in high PD-L1, 64.0% vs 49.2% in low PD-L1, and 54.5% vs 32.3% in negative PD-L1 expression. The safety profile remains favorable with no new safety signals. Additional data updates are expected at a medical conference later in 2025.

Positive

• High overall response rate of 60.8% and disease control rate of 90.2% across all PD-L1 expression levels
• Significant improvement compared to historical controls, especially in patients with lower PD-L1 expression
• Strong efficacy in hard-to-treat patient population (92% of patients with PD-L1 TPS <50%)
• Favorable safety profile with no new safety signals
• Data from 165 patients across two trials showing consistent improvements in response rates

Negative

• Additional trial data updates pending until later in 2025
• Small sample size for high PD-L1 expression group (only 4 patients)

Insights

Oncology Clinical Researcher

Immutep's triple therapy shows impressive response rates for lung cancer patients, particularly benefiting underserved PD-L1 low expressors.

The INSIGHT-003 trial results represent a significant clinical advancement in first-line NSCLC treatment. The triple combination of efti (eftilagimod alpha), pembrolizumab, and chemotherapy achieved a 60.8% overall response rate and 90.2% disease control rate across all patients - substantially outperforming historical controls.

What's particularly striking is the efficacy in typically hard-to-treat patient populations. About 92% of enrolled patients had PD-L1 expression below 50%, including 43% with PD-L1 below 1%. These patients with low PD-L1 expression traditionally respond poorly to immunotherapy. Yet this combination showed a 59.6% response rate in PD-L1 <50% patients compared to historical 40.8%.

The most remarkable improvement was seen in PD-L1 negative (<1%) patients, where the triple therapy achieved 54.5% ORR versus historical 32.3% - a 68.7% relative improvement. This suggests efti effectively sensitizes these traditionally immunotherapy-resistant tumors.

The favorable safety profile further strengthens the clinical potential. These results validate the design of the pivotal TACTI-004 Phase III trial using the same combination and strongly suggest efti could establish a new standard of care, particularly for the majority of NSCLC patients with low PD-L1 expression who currently have limited treatment options.

• Novel combination achieves 60.8% response rate and 90.2% disease control rate in first-line non-small cell lung cancer (1L NSCLC)
• Notably, ~92% of all evaluable patients have PD-L1 TPS <50%, including 43% with PD-L1 below 1 (TPS <1%), who represent an area of high unmet need
• Data demonstrates significant improvement in response rates compared to historical controls, and safety continues to be favourable
• Multi-centre INSIGHT-003 is evaluating the same immunotherapy/chemotherapy combination used in the pivotal TACTI-004 Phase III in 1L NSCLC
• Additional data from INSIGHT-003 is planned for presentation at a medical conference later this year
  
  

SYDNEY, AUSTRALIA, May 15, 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 that a 60.8% response rate and 90.2% disease control rate, according to RECIST1.1, has been achieved in the investigator-initiated INSIGHT-003 trial as of the data-cut off date of 06 May 2025. INSIGHT-003 is evaluating eftilagimod alpha (efti) in combination with the anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC).

Marc Voigt, CEO of Immutep, stated, “Our level of confidence in efti driving a new standard of care for patients with non-small cell lung cancer via our pivotal TACTI-004 trial continues to rise with the strength of the data from INSIGHT-003 and TACTI-002. Across two trials we have now efficacy data from 165 patients with 1L NSCLC who have been treated with efti and KEYTRUDA, either with or without chemotherapy. In multi-national settings, efti has generated consistent and remarkable improvements in response rates. In particular, the interim ORR data in patients with PD-L1 expression below 50% in the ongoing INSIGHT-003 trial, who represent over two-thirds of the 1L NSCLC patient population, is very encouraging.”

Majority of Patients have PD-L1 TPS <50%
Notably, ~92% of all evaluable patients (N=51) in the INSIGHT-003 study have PD-L1 TPS <50%. This includes 49% of patients with PD-L1 Tumour Proportion Score (TPS) of 1-49% and 43% of patients with PD-L1 TPS <1%, as shown in the table below.

Strong Response Rates Across All PD-L1 Expression Levels
Data from all evaluable patients demonstrates significant improvement of Overall Response Rate (ORR) according to RECIST 1.1 across all levels of PD-L1 expression compared to historical control from a registrational trial of anti-PD-1 and doublet chemotherapy in non-squamous 1L NSCLC¹:

• 75.0% ORR versus 62.1% ORR in patients with high PD-L1 expression (TPS >50%)
• 64.0% ORR versus 49.2% ORR in patients with low PD-L1 expression (TPS 1-49%)
• 54.5% ORR versus 32.3% ORR in patients with negative PD-L1 expression (TPS <1%)
  
  

The 60.8% response rate regardless of PD-L1 expression (TPS 0-100%) represents a substantial improvement compared to historical control of 48.0%.¹ The relative outperformance is particularly strong given the registrational trial has four times as many patients with high PD-L1 expression (~32% of patients versus ~8% in INSIGHT-003), who have the highest response rates.

Importantly, in patients with TPS <50% (N=47), who have a high unmet need and represent over two-thirds of the 1L NSCLC patient populaton, the triple combination with efti achieved a 59.6% response rate as compared to historical control of 40.8%.¹

INSIGHT-003 Overall Response Rate & Disease Control Rate, according to RECIST1.1
PD-L1 Expression Levels	TPS 0-100% (N=51)	TPS <1% (N=22)	TPS 1-49% (N=25)	TPS <50% (N=47)	TPS ≥50% (N=4)
ORR %	60.8	54.5	64.0	59.6	75.0
DCR %	90.2	86.4	92.0	89.4	100

Safety
Safety continues to be favourable for the triple combination in 1L NSCLC with no new safety signals.

Next Steps
Additional data updates from this trial are expected to be presented at a medical conference in 2025 and beyond.

About INSIGHT-003
INSIGHT-003 is an investigator-initiated study conducted by the Frankfurt Institute of Clinical Cancer Research IKF and several other German centres. It is being run as the third arm (Stratum C) of the ongoing Phase I INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. The study is evaluating a triple combination therapy in front-line non-small cell lung cancer patients consisting of efti administered subcutaneously in conjunction with an existing approved standard-of-care combination of anti-PD-1 therapy (pembrolizumab) and chemotherapy (carboplatin and pemetrexed) delivered intravenously. The trial will assess the safety, tolerability, and initial efficacy of the combination.

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.

_{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}

_{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 are the response rates achieved by IMMP's efti combination therapy in first-line NSCLC?

The combination therapy achieved a 60.8% overall response rate and 90.2% disease control rate across all PD-L1 expression levels in first-line NSCLC patients.

How does IMMP's treatment perform in patients with low PD-L1 expression?

In patients with PD-L1 TPS <50%, the treatment achieved a 59.6% response rate compared to historical control of 40.8%, showing significant improvement in this hard-to-treat population.

What is the safety profile of Immutep's efti combination therapy?

The safety profile continues to be favorable for the triple combination therapy in first-line NSCLC with no new safety signals reported.

How many patients were included in IMMP's INSIGHT-003 trial?

The trial included 51 evaluable patients, with approximately 92% having PD-L1 TPS <50%, including 43% with PD-L1 below 1%.

When will additional data from IMMP's INSIGHT-003 trial be presented?

Additional data updates from the trial are expected to be presented at a medical conference later in 2025.