SYDNEY, Australia, July 13, 2026
Immutep announced positive mature overall survival data from its investigator-initiated Phase 1 INSIGHT-003 trial evaluating eftilagimod alfa (efti) in combination with KEYTRUDA® (pembrolizumab) and chemotherapy as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC). Presented with a minimum follow-up of 30 months, the study demonstrated a median overall survival (mOS) of 30.9 months in both the overall patient population and in patients with low or no PD-L1 expression (TPS <50%), comparing favorably with historical benchmarks for standard immunotherapy and chemotherapy combinations. Alongside the encouraging INSIGHT-003 findings, the company also provided an update on its ongoing investigation into the discontinued Phase 3 TACTI-004 study, highlighting preliminary immune monitoring observations that may help explain the differing clinical outcomes.
INSIGHT-003 Demonstrates Encouraging Long-Term Survival
The INSIGHT-003 study enrolled 51 evaluable patients with advanced non-squamous NSCLC, approximately 92% of whom had low or negative PD-L1 expression, a group that typically derives less benefit from PD-1 inhibitor-based therapies. Mature analysis showed a median overall survival of 30.9 months in both the entire study population and the subgroup with TPS below 50%, while the small subgroup with PD-L1 expression of at least 50% achieved a median overall survival of 37.8 months. The company noted that these outcomes compare favorably with historical registrational studies reporting approximately 22 months median overall survival for similar treatment regimens. Importantly, no new safety concerns were identified compared with previous analyses, supporting the continued evaluation of efti as an immune-activating therapy designed to enhance responses to checkpoint inhibitors and chemotherapy.
Preliminary Immune Findings May Explain TACTI-004 Outcome
Immutep also shared an update on the ongoing root cause analysis of the discontinued TACTI-004 Phase 3 trial. The study was halted earlier this year following a planned interim futility analysis after the combination of standard therapy plus efti failed to demonstrate superiority over standard therapy plus placebo. Preliminary immune monitoring data now suggest that patients receiving efti in TACTI-004 exhibited a markedly different immune activation profile compared with nearly 600 patients treated across five previous clinical studies, including INSIGHT-003. Researchers observed differences in circulating lymphocyte and monocyte responses, findings that may provide important biological insights into the unexpected trial outcome. The company continues to investigate additional contributing factors, including manufacturing-related variables, in collaboration with development partners Dr. Reddy’s Laboratories and WuXi Biologics, with further results expected during the third quarter of 2026.
Advertisement
Efti Development Continues Across Multiple Solid Tumor Programs
Eftilagimod alfa is a novel LAG-3 MHC Class II agonist designed to activate antigen-presenting cells and stimulate both innate and adaptive anti-tumor immune responses. The immunotherapy continues to be evaluated across multiple solid tumor indications, including NSCLC, head and neck squamous cell carcinoma, breast cancer, and soft tissue sarcoma. The therapy has previously received FDA Fast Track designation for both first-line NSCLC and first-line head and neck cancer. While the company works to better understand the divergent findings from TACTI-004, the strong survival outcomes observed in INSIGHT-003 reinforce confidence in efti’s potential to enhance anti-tumor immunity, particularly in patients with limited PD-L1 expression who continue to face significant unmet clinical needs.
Source: Immutep, press release
