The investigator-initiated Phase I trial was 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).
According to Immutep, 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 first-line non-small cell lung cancer patients.
Notably, 81% of patients had a PD- L1 Tumor Proportion Score (TPS) of less than 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 less than 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.
This population yielded an ORR of 48% regardless of PD-L1 expression and a response rate of 40.8% in patients with PD-L1 TPS less than 50%.
“Immutep has made significant progress with our late-stage development planning to treat one of the largest cancer indications globally,” said Dr. Frédéric Triebel, chief scientific officer at Immutep.
“We are uniquely positioned to address PD-L1 low (TPS 1-49%) and high (TPS greater than 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.”
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 enrol 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.