Eftilagimod Alfa Combo Shows Positive Overall Survival in Advanced NSCLC

Combining eftilagimod alfa (efti) with pembrolizumab (Keytruda) and chemotherapy produced positive overall survival (OS) data as frontline treatment for patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to a press release on findings from the phase 1 INSIGHT-003 trial (NCT03252938).¹

What did data from the INSIGHT-003 trial show?

Among 51 evaluable patients with nonsquamous disease, the median OS was 30.9 months in the overall population after a minimum follow-up of 30 months. The median OS was 30.9 months in patients with a PD-L1 tumor proportion score (TPS) of less than 50% (n = 47) and 37.8 months among those with a PD-L1 TPS of at least 50% (n = 4).

The results observed in INSIGHT-003 appear to compare favorably with a median OS of 22.0 months observed in a registrational trial assessing anti–PD-1 treatment plus doublet chemotherapy among patients with frontline nonsquamous NSCLC.² Of note, patients with a PD-L1 TPS of less than 50% were overrepresented in INSIGHT-003 (approximately 92%) compared with this historical benchmark (68%).

The trial demonstrated no new safety signals since the previous data cutoff.

“We are encouraged by the mature [OS] data from INSIGHT-003 in [first-line] nonsquamous NSCLC, which continue to compare favorably with historical benchmarks, particularly given the high proportion of patients in this study with no or low PD-L1 expression,” Marc Voigt, chief executive officer at Immutep, the developer of efti, said in the press release.¹ “The observed median [OS] of 30.9 months especially in patients with no or low PD-L1 expression reinforces our confidence in efti’s potential to enhance anti-tumor immune responses, including in patient populations that have historically experienced less favorable outcomes.”

What is the INSIGHT platform?

INSIGHT-003 represents one stratum of the INSIGHT platform, which was designed to evaluate the immune-activating effects of efti in combination with immunotherapeutic, targeted, and chemotherapeutic agents or via new routes of application across different advanced solid tumors.³ Evaluated tumor types under the INSIGHT platform included NSCLC, urothelial carcinoma, metastatic renal cell carcinoma, and breast carcinoma.

The trial’s primary end point was the feasibility rate, or the rate of patients receiving study therapy without dose-limiting toxicities. Secondary end points included adverse effects, responses per RECIST v1.1 guidelines, progression-free survival, OS, and immune response in the whole blood and tumor tissue.

What is efti, and what is its history?

The developers engineered efti as an investigational immunotherapy that directly activates antigen-presenting cells (APCs) through the MHC Class II pathway. This process may engage the adaptive and innate immune system to facilitate a broad anti-cancer immune response. Investigators are currently evaluating the agent across different solid tumors such as NSCLC, head and neck squamous cell carcinoma, soft tissue sarcoma, and breast cancer.

In March 2026, developers discontinued the phase 3 TACTI-004 trial (NCT06726265) assessing efti plus pembrolizumab and chemotherapy among those with frontline NSCLC following a planned interim futility analysis.⁴ Among 173 evaluable patients, data showed an overall response rate (ORR) of 42.9% with efti plus standard of care (SOC) vs 55.1% with SOC alone. Pending a final analysis, investigators have reported no new safety signals in the TACTI-004 trial.

Analysis of the TACTI-004 trial remains ongoing, with further results anticipated in the third quarter of 2026.

“[W]e 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,” Voigt concluded.¹

References

1. Immutep provides clinical update in 1st line NSCLC: positive mature overall survival data from INSIGHT-003 and update from TACTI-004. News release. Immutep Limited. July 13, 2026. Accessed July 14, 2026. https://tinyurl.com/2s38bkdz
2. Gadgeel S, Rodríguez-Abreu D, Speranza G, et al. Updated analysis from KEYNOTE-189: pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol. 2020;38(14):1505-1517. doi:10.1200/JCO.19.03136
3. Feasibility and safety of IMP321 (Eftilagimod Alpha) for advanced stage solid tumors (INSIGHT). ClinicalTrials.gov. Updated February 19, 2026. Accessed July 14, 2026. https://tinyurl.com/ydjnn5u4
4. TACTI-004 phase III study in first line NSCLC to be discontinued following futility analysis. News release. Immutep Limited. March 13, 2026. Accessed July 14, 2026. https://tinyurl.com/mr3a7bf7