INSIGHT-003 Trial of Eftilagimod Alpha Combo in NSCLC Completes Enrollment
The phase 1 INSIGHT-003 trial of efti, pembrolizumab, and chemotherapy for first-line advanced nonsquamous NSCLC has completed enrollment.
Lungs: © Mopic - stock.adobe.com
The investigator-initiated, multicenter, phase 1 INSIGHT-003 trial (NCT03252938) evaluating the combination of eftilagimod alpha (efti; IMP321) with the anti–PD-1 therapy pembrolizumab (Keytruda) and doublet chemotherapy as a first-line treatment option for patients with advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) has completed patient enrollment.1
Approximately 50 evaluable patients have now been enrolled across multiple clinical sites in Germany. The study is being led by the Frankfurt Institute of Clinical Cancer Research IKF.
In November 2024, overall survival (OS) results from INSIGHT-003 were reported, showing promising results in terms of OS and progression-free survival (PFS) in this patient population. With a minimum follow-up of 22 months (n = 21), patients given the combination of efti, pembrolizumab, and chemotherapy achieved a median OS of 32.9 months and a 24-month OS rate of 81.0%.1
Initial results from the study compare favorably to data from the phase 3 KEYNOTE-189 trial (NCT02578680).2 In this study and at a median follow-up of 23.1 months, patients given pembrolizumab plus chemotherapy alone (n = 410) had a median OS of 22.0 months (95% CI, 19.5-25.2) and a median PFS of 9.0 months (95% CI, 8.1-9.9).2
Among the 40 evaluable patients, the combination of efti, pembrolizumab, and chemotherapy led to an overall response rate (ORR) of 55.0% and a disease control rate of 87.5%.3 Among those with a PD-L1 tumor proportion score (TPS) of more than 50% (n = 4), the ORR was 75.0%. In patients with a PD-L1 TPS of 1% to 49% (n = 17), the ORR was 58.8%. Additionally, the ORR was 47.4% among those with a PD-L1 TPS of less than 1% (n = 19).
For safety, no new safety signals were observed with the combination.
Additional findings from INSIGHT-003 are expected in 2025 and beyond.1
About the Phase 1 INSIGHT-003 Trial
INSIGHT-003 is an investigator-initiated study that is being run as the third arm of the ongoing phase I INSIGHT trial. The combination of efti, pembrolizumab, and chemotherapy is being evaluated for the treatment of patients aged 18 years of age or older with histologically confirmed locally advanced or metastatic solid tumors.4 Stratum C includes patients with NSCLC adenocarcinomas who were slated to receive standard pembrolizumab plus chemotherapy.
Patients with an ECOG performance status of 0 or 1, those with adequate hematological, hepatic and renal function and evidence of measurable disease or assessable disease per RECIST 1.1 criteria, and those with a life expectancy of 3 months or more were eligible for enrollment in the study.
The primary end point of the study is the feasibility rate of treatment, and secondary end points included PFS, OS, overall response rate, incidence and severity of adverse events, and immune response in whole blood and tumor tissue.
REFERENCES:
Patient enrolment completed for INSIGHT-003. News release. Immutep Limited. January 6, 2024. Accessed January 6, 2025. https://tinyurl.com/k7nupyd6
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
Immutep’s efti shows excellent survival data from INSIGHT-003 trial in non-small cell lung cancer. News release. Immutep. November 14, 2024. Accessed January 6, 2025. https://tinyurl.com/yc5vter3
Feasibility and safety of IMP321 (eftilagimod alpha) for advanced stage solid tumors. ClinicalTrials.gov. Updated November 7, 2024. Accessed January 6, 2025. https://clinicaltrials.gov/study/NCT03252938
