Clinical-stage biotechnology company Immutep Limited (ASX: IMM) has received 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).
“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,” Professor Dr. Salah-Eddin Al-Batran of the Frankfurt Institute of Clinical Cancer Research IKF and project lead stated.
“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 data 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.
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,” Immutep CSO, Dr. Frédéric Triebel, said.
“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.
