Posted: 29 May 2023
Immutep Limited, a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announces new encouraging clinical data in 1st line non-small cell lung cancer from INSIGHT-003, an investigator-initiated Phase I trial conducted by the Frankfurt Institute of Clinical Cancer Research IKF. INSIGHT-003 is the first study evaluating eftilagimod alpha (“efti”), a soluble LAG-3 protein and MHC Class II agonist, in conjunction with standard-of-care anti-PD-1 therapy and doublet chemotherapy (carboplatin/pemetrexed).
The triple combination therapy remains well-tolerated and continues to show promising initial efficacy signals attaining a 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). Notably, 81% (17/21) of patients had a PD-L1 Tumor Proportion Score (TPS) of <50%, who are less responsive to anti-PD-1 based therapy compared with PD-L1 high expressing patients.
The 67% ORR regardless of PD-L1 expression and 65% response rate in patients with PD-L1 TPS <50% for the triple combination compare favourably to reported results from a registrational trial of anti-PD-1 and doublet chemotherapy in the same patient population that yielded an ORR of 48% regardless of PD-L1 expression and a response rate of 40.8% in patients with PD-L1 TPS <50%.
Immutep CSO, Dr. Frédéric Triebel, said: “Immutep has made significant progress with our late-stage development planning to treat one of the largest cancer indications globally. We are uniquely positioned to address PD-L1 low (TPS 1-49%) and high (TPS >50%) expressing patients, representing roughly 65% of the non-small cell lung cancer patient population, with powerful chemo-free IO-IO approaches, and potentially the entire patient population when including the IO-IO-chemo combination being tested in INSIGHT-003. Powering both options is eftilagimod alpha, the only MHC Class II agonist in clinical development, safely generating a broad immune response to fight cancer.”
Patients with high, low, and negative PD-L1 expression represent approximately 30%, 35%, and 35%, respectively, of the 1st line non-small cell lung cancer (1L NSCLC) patient population. Low and negative PD-L1 expressors (patients with a PD-L1 TPS of 1-49% and <1%) are less responsive to anti-PD-(L)1 therapy compared to patients with high levels or PD-L1 TPS of ≥50%.
Unlike many immuno-oncology combinations (IO-IO) that focus on high PD-L1 expressing patients, compelling clinical results to date from the TACTI-002 Phase II trial suggest that efti may be uniquely positioned to effectively address low and high PD-L1 expressors (~65% of 1L NSCLC patient population) through chemo-free IO-IO combinations, and potentially the entire NSCLC patient population, regardless of PD-L1 expression, when adding the IO-IO-chemo triple combination.
Prof. Dr. Salah-Eddin Al-Batran of the Institute of Clinical Cancer Research IKF and lead investigator noted: “These initial results are supportive of efti’s synergies with both anti-PD-1 therapy and chemotherapy in the clinical setting, and we are pleased with the data to date from this novel IO-IO-chemo combination. Efti’s ability to safely engage such a robust immune response for cancer patients via MHC Class II agonism is truly unique, and we look forward to providing more data from this triple combination therapy at a major medical conference this year.”
The INSIGHT-003 trial was recently expanded to enroll 50 patients across multiple sites based on the favourable safety and efficacy results, and additional data is expected to be presented at a major medical conference in H2 CY2023.
