Immutep (ASX:IMU) has reported mature overall survival data from the investigator‑initiated INSIGHT‑003 trial that it says offer a hopeful signal for eftilagimod alfa, known as efti, in first-line non‑squamous non‑small cell lung cancer (NSCLC).
The Phase 1 trial is evaluating alfa in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) and chemotherapy.
With a data cutoff of March 2026, the Phase 1 study of 51 evaluable patients recorded a median overall survival of 30.9 months in the overall population and the same 30.9 months in the subgroup with Tumour Proportion Score (TPS) below 50 per cent.
Patients with TPS 50 per cent or greater had a median overall survival of 37.8 months. Approximately 92 per cent of INSIGHT‑003 participants had no or low PD‑L1 expression, a group historically less responsive to PD‑1 inhibitor‑based therapies and overrepresented in this study compared to previous benchmarks.
Immutep said the INSIGHT‑003 outcomes compare favourably with a registrational trial benchmark of 22-month median overall survival for anti‑PD‑1 plus chemotherapy in non‑squamous first-line NSCLC, and reported an objective response rate of 62.7 per cent in INSIGHT‑003 despite the high proportion of low-PD-L1 patients. No new safety signals were identified as of the latest cutoff, it said.
Those positive findings are being weighed against the March 2026 decision to discontinue the global TACTI‑004 Phase 3 trial after an interim futility analysis recommended by the Independent Data Monitoring Committee.
In the TACTI‑004 analysis of 173 patients, the objective response rate was 42.9 per cent in the standard‑of‑care plus efti arm versus 55.1 per cent in the standard‑of‑care plus placebo arm, with the difference seen across squamous and non‑squamous histologies and no superiority in any TPS subgroup. Immutep says no new safety signals have emerged in TACTI‑004 to date.
Preliminary immune monitoring from TACTI‑004 suggested that patients treated with efti displayed a markedly different immune activation profile compared with prior studies and observations from INSIGHT‑003, based on analyses of absolute lymphocyte and circulating monocyte counts.
Immutep is conducting a comprehensive root cause analysis that includes evaluation of manufacturing and other potential factors, with additional results expected in the third quarter of the calendar year 2026.
Marc Voigt, CEO of Immutep, said, “We are encouraged by the mature overall survival data from INSIGHT‑003 in 1st line non‑squamous NSCLC, which continue to compare favourably with historical benchmarks, particularly given the high proportion of patients in this study with no or low PD‑L1 expression. The observed median overall survival of 30.9 months, especially in patients with no or low PD‑L1 expression, reinforces our confidence in efti’s potential to enhance anti-tumour immune responses, including in patient populations that have historically experienced less favourable outcomes.
"At the same time, we are completing a comprehensive root cause analysis of TACTI‑004 to better understand the factors underlying the outcome of that trial and their implications for the potential future development of efti. Importantly, the differences observed in the immune activation profile between TACTI‑004 and prior studies are providing valuable insights to inform our strategy as we evaluate efti’s potential path forward.”
Efti is an MHC Class II agonist that activates antigen-presenting cells to engage adaptive and innate anti‑tumour immunity. The agent is being evaluated across multiple solid tumour types and has previously received Fast Track designation from the US FDA for first-line head and neck squamous cell carcinoma and first-line NSCLC.
