Immutep Unveils Hopeful Results of Triple Therapy in INSIGHT-003 Trial

Immutep Limited (ASX:IMM; NASDAQ:IMMP), a clinical-stage biotechnology company developing innovative LAG-3 immunotherapies for cancer and autoimmune diseases, is excited to share new promising clinical data from INSIGHT-003. INSIGHT-003 is the first study to evaluate eftilagimod alpha (“efti”), a soluble LAG-3 protein and MHC Class II agonist, in combination with standard-of-care anti-PD-1 therapy and doublet chemotherapy (carboplatin/pemetrexed) in 1st line non-small cell lung cancer. With these promising findings, we are encouraged to continue our research to improve patient outcomes for this challenging and deadly disease.

The triple combination therapy has demonstrated astonishing initial efficacy signals, exemplified by an impressive 67% overall response rate (ORR) and 91% disease control rate (DCR) in advanced or metastatic non-squamous, 1st line non-small cell lung cancer patients (N=21).

Even more remarkable is that 81% (17/21) of these patients had a PD-L1 Tumor Proportion Score (TPS) of <50%, which is a population that is usually less responsive to anti-PD-1 based treatments. This heralds hope that this promising therapy remains well-tolerated.

The remarkable results of the triple combination therapy showed a 67% overall response rate (ORR) regardless of PD-L1 expression, and an even more impressive 65% response rate in patients with PD-L1 TPS <50%. These results far exceed the outcomes reported from a registrational trial of anti-PD-1 and doublet chemotherapy, which only achieved an ORR of 48% and a response rate of 40.8% in the same patient population.

Dr. Frédéric Triebel, CSO of Immutep, is encouraged by the progress the company has made with its late-stage development plan to target cancer, one of the planet’s most devastating illnesses. Thanks to Immutep’s innovative chemo-free IO-IO approaches, the company is positioned to battle PD-L1 low (TPS 1-49%) and high (TPS >50%) expressing patients—which comprise around 65% of non-small cell lung cancer cases.

With the potentially revolutionary IO-IO-chemo combination, now being tested in INSIGHT-003, Immutep is in a prime position to potentially treat the entire patient population. This is made possible through the MHC Class II agonist, eftilagimod alpha, which safely triggers a broad immune response to fight cancer.

In the 1st line non-small cell lung cancer (1L NSCLC) patient population, about a third of patients have high PD-L1 expression (PD-L1 TPS of ≥50%), a third have low PD-L1 expression (PD-L1 TPS of 1-49%), and a third have no PD-L1 expression (<1%). Unsurprisingly, these classifications determine a patient’s response to anti-PD-(L)1 therapy: those with high PD-L1 expression are most likely to respond positively, while those with low and negative PD-L1 expression are less likely to benefit from this treatment.

The groundbreaking results of the TACTI-002 Phase II trial suggest that efti could be a breakthrough in treating low and high PD-L1 expressing non-small-cell lung cancer patients through a chemo-free immuno-oncology double combination. This therapy has the potential to seek out and treat the entire patient population, regardless of PD-L1 expression, when combined with a triple combination of immuno-oncology-chemotherapy.

Prof. Dr. Salah-Eddin Al-Batran of the Institute of Clinical Cancer Research IKF is thrilled with the initial results of this novel IO-IO-chemo combination that can effectively engage a powerful immune response for cancer patients through MHC Class II agonism. This combination therapy has revealed synergies with both anti-PD-1 therapy and chemotherapy, and the team looks forward to presenting more detailed data from this triple combination at a major medical conference this year.

The INSIGHT-003 trial has seen great progress – with favourable safety and efficacy results, it has been expanded to enrol 50 patients across multiple sites! Even more data is anticipated to be shared at a major medical conference in H2 CY2023. It’s sure to be an exciting time for all involved in this trial!

About INSIGHT-003

Prof. Dr. Salah-Eddin Al-Batran of the Institute of Clinical Cancer Research IKF is leading the way with their third arm of the ongoing Phase I INSIGHT trial – INSIGHT-003. This trial is evaluating a triple combination therapy for front line non-small cell lung cancer patients which includes subcutaneous administration of efti to be administered alongside an established standard of care combination of intravenous anti-PD-1 (pembrolizumab) and chemotherapy (carboplatin and pemetrexed). This exciting study aims to assess the safety, tolerability, and initial efficacy of such a unique combination of treatments.

About Eftilagimod Alpha (Efti)

Efti is an innovative and cutting-edge technology from Immutep, designed to combat cancer by stimulating both the innate and adaptive immune systems of our body. Uniquely developed as a soluble LAG-3 protein and MHC Class II agonist, it binds to major histocompatibility complex molecules present on antigen presenting cells, triggering the activation and proliferation of various immune cells, including CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. Furthermore, it dramatically increases the expression of molecules like IFN-ƴ and CXCL10, significantly strengthening our body’s ability to fight cancer.

Evaluation of Efti is underway for various forms of solid tumors, among them non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Thanks to its safety profile, it encourages various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy, and has been granted Fast Track Designation by the United States Food and Drug Administration (FDA) for 1st line HNSCC and 1st line NSCLC.

About Immutep

Immutep is revolutionizing the world of immunotherapy by harnessing the unique power of Lymphocyte Activation Gene-3 (LAG-3). As a clinical stage biotechnology company, we are pioneering the development of novel therapies for those suffering from cancer and autoimmune diseases.

Our innovative product portfolio is dedicated to providing powerful new treatment options to bring relief to those in need and create value for our shareholders. We are committed to continuing our innovative progress for the betterment of those affected.

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