Immutep reported a 30.9-month median overall survival in the Phase I INSIGHT-003 trial of eftilagimod alfa (efti) plus pembrolizumab and chemotherapy for first-line non-squamous NSCLC. The company also provided an update on the ongoing TACTI-004 Phase III root cause investigation.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Immutep has reported mature overall survival data from the investigator-initiated Phase I INSIGHT-003 trial (NCT03252938) evaluating eftilagimod alfa (efti) in combination with KEYTRUDA® (pembrolizumab) and platinum-based chemotherapy as first-line treatment for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). After a minimum follow-up of 30 months, the combination achieved a median overall survival (mOS) of 30.9 months in both the overall study population (N=51) and in patients with low or absent PD-L1 expression (tumor proportion score [TPS] <50%; N=47), a group that typically derives less benefit from PD-1 inhibitor-based therapy.
Mechanism of Action: APC Activation
Efti is a first-in-class MHC Class II agonist that activates antigen-presenting cells, including dendritic cells and monocytes. This mechanism stimulates both innate and adaptive immune responses, promoting cytotoxic T-cell activation and broader anti-tumor immunity.
The therapy is under clinical evaluation across several solid tumors, including NSCLC, head and neck squamous cell carcinoma, breast cancer, and soft tissue sarcoma. The U.S. Food and Drug Administration has granted Fast Track designation to efti for first-line NSCLC and first-line head and neck squamous cell carcinoma.
Comparison to Historical Benchmarks
The INSIGHT-003 analysis included 51 evaluable patients with advanced non-squamous NSCLC. Approximately 92% of participants had TPS below 50%, representing a population with substantial unmet clinical need.
At the March 27, 2026 data cutoff, median overall survival reached 30.9 months in both the overall cohort and the TPS <50% subgroup. Among the four patients with TPS ≥50%, median overall survival was 37.8 months.
According to Immutep, these outcomes compare favorably with the 22.0-month median overall survival reported in historical registrational studies of pembrolizumab plus platinum-doublet chemotherapy in first-line non-squamous NSCLC. No new safety signals emerged during extended follow-up.
TACTI-004 Divergence Under Investigation
The update also included progress on the ongoing root cause analysis of the Phase III TACTI-004 trial (NCT06726265), which was discontinued in March 2026 following a planned interim futility analysis recommended by the Independent Data Monitoring Committee.
Among 173 evaluable patients, the objective response rate was 42.9% in the efti arm compared with 55.1% in the placebo arm, with no evidence of superiority across squamous or non-squamous disease or any PD-L1 subgroup. This contrasted with the 62.7% objective response rate previously reported in INSIGHT-003.
Preliminary immune monitoring data indicate that patients treated with efti in TACTI-004 exhibited a markedly different immune activation profile than patients enrolled in INSIGHT-003 and five earlier clinical studies involving nearly 600 participants. The differences were observed through analyses of absolute lymphocyte counts and circulating monocyte levels.
The company is continuing to investigate potential contributing factors, including manufacturing-related variables, in collaboration with partners Dr. Reddy’s Laboratories and WuXi Biologics.
Company Expects Additional Findings in Third Quarter of 2026
Chief Executive Officer Marc Voigt said the mature survival data from INSIGHT-003 strengthen confidence in efti’s ability to improve anti-tumor immune responses, particularly in patients with low PD-L1 expression who historically experience poorer outcomes with standard immunotherapy.
Immutep expects to complete additional analyses from the TACTI-004 root cause investigation during the third quarter of 2026, which will help determine the future clinical development strategy for efti in NSCLC.
Reference
Immutep | LAG-3 Immunotherapy for Cancer & Autoimmune Disease
About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.