Full Press Release Details
Immutep Reports Promising Clinical Data from INSIGHT-003 Trial
at ESMO Congress 2023
SYDNEY, AUSTRALIA 24 October 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ( Immutep or the
Company ), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today provides an overview of the promising clinical data from the
investigator-initiated INSIGHT-003 trial. The study evaluates a triple combination of eftilagimod alpha ( efti ), a soluble LAG-3 protein and MHC Class II
agonist, with anti-PD-1 therapy (pembrolizumab) and doublet chemotherapy (carboplatin/pemetrexed) as front-line therapy for metastatic or advanced non-squamous non-small cell lung cancer (NSCLC).
Prof. Dr. Salah-Eddin
Al-Batran of the Frankfurt Institute of Clinical Cancer Research IKF and project lead stated: Our broad experience evaluating efti across numerous solid tumour indications as monotherapy and in combination with immune checkpoint inhibitors has
furthered our understanding of the complementary mechanisms of action at play with this novel MHC class II agonist. We are building deeper insights into how efti jumpstarts the immune system to fight cancer through activation of dendritic cells, and
its synergy with anti-PD-1 therapy. Now with this IO-IO-chemotherapy combination,
cytotoxic CD8+ T cells that are activated and significantly proliferate via efti can be armed with chemo-induced tumour antigens to drive an even greater immune response. We re seeing early yet powerful results, especially in low and negative PD-L1 expressing patients in need of new therapies to combat cancer.
The poster presentation at ESMO Congress
2023 showed the triple combination therapy continues to be well-tolerated with strong signals of efficacy. The clinical data1 included a positive median Overall Survival (OS) that was not reached
and encouraging median Progression Free Survival (PFS) of 10.1 months. Additionally, the IO-IO-chemo combination achieved a 71.4% Overall Response Rate (ORR) 90.5%
Disease Control Rate (DCR), and showed positive early trends in 12-month OS and PFS rates.
Notably, 81% (17/21)
of patients in the trial had a PD-L1 Tumor Proportion Score (TPS) of <50%, including PD-L1 negative (TPS <1%) and PD-L1 low
(TPS 1-49%), who are less responsive to anti-PD-1 based therapy as compared to PD-L1 high
(TPS >50%) patients. In this difficult-to-treat NSCLC patient population with PD-L1
TPS <50%, the triple combination s 70.6% ORR 10.9-month median PFS (TPS 1-49%) and 10.1 month median PFS
(TPS <1%) compare favourably to the reported 40.8% response rate, 9.2-month median PFS (TPS 1-49%), and 6.2-month median PFS
(TPS <1%) from a registrational trial of anti-PD-1 and doublet chemotherapy.2 Furthermore, the triple combination
appears to be safe, and the addition of efti does not appear to increase the toxicity of the standard chemo-immunotherapy regimen.
Best Overall Response from Baseline by PD-L1 Status
Immutep CSO, Dr. Fr d ric Triebel, said: Immutep continues to prioritise non-small cell lung cancer, one of the largest cancer indications globally, as the most significant area of focus in our late-stage development pipeline. The compelling data that our proprietary MHC Class II
agonist has generated in combination with immune checkpoint inhibitors for NSCLC patients positions efti as one of the more promising clinical candidates in immuno-oncology today. This is applicable regardless of patient PD-L1 expression, and particularly in patients with negative or low PD-L1 levels who typically respond poorly to checkpoint treatment and for which we see strong potential
with this IO-IO-chemo combination.
Patients with high, low, and
negative PD-L1 expression represent approximately 30%, 35%, and 35%, respectively, of the metastatic non-small cell lung cancer patient population. Unlike many
immuno-oncology (IO) combinations that focus on high PD-L1 expressing patients, compelling clinical results to date from efti s clinical trials suggest it may be uniquely positioned to effectively address
low and high PD-L1 expressors through chemo-free IO-IO combinations, and potentially the entire NSCLC patient population with a focus on patients with TPS <50% with IO-IO-chemo combinations.
INSIGHT-003 is an investigator-initiated study conducted
by the Frankfurt Institute of Clinical Cancer Research IKF. 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 Alpha (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- 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 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).
Immutep is a clinical-stage biotechnology
company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique 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.
Australian Investors/Media:
+61 (0)406 759 268; cstrong@citadelmagnus.com
Chris Basta, VP, Investor Relations and
Corporate Communications
+1 (631) 318 4000; chris.basta@immutep.com
This announcement was authorised for release by the Board of Immutep Limited.
Immutep Limited, Level 33, Australia Square, 264 George Street, Sydney NSW 2000, Australia