First-Line Eftilagimod Alpha Plus Pembrolizumab/Chemo Yields Responses in Advanced Nonsquamous NSCLC

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The addition of eftilagimod alpha (efti; IMP321) to pembrolizumab (Keytruda) and chemotherapy led to high rates of responses and disease control in the first-line treatment of patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC), according to data from the INSIGHT-003 trial, which is stratum C in the phase 1 INSIGHT study (NCT03252938).1

Findings announced by Immutep showed that as of the May 6, 2025, data cutoff, patients in the overall population of INSIGHT-003 (n = 51) achieved an overall response rate (ORR) of 60.8% and a disease control rate (DCR) of 90.2%. When broken down by PD-L1 tumor proportion score (TPS), the ORRs for patients with a TPS of less than 1% (n = 22), 1% to 49% (n = 25), less than 50% (n = 47), and at least 50% (n = 4) were 54.5%, 64.0%, 59.6%, and 75.0%, respectively. The respective DCRs in these subgroups were 86.4%, 92.0%, 89.4%, and 100%.

According to Immutep, ORR data surpassed historical controls for the overall population (60.8% vs a historical control of 48.0%), for patients with a PD-L1 TPS of at least 50% (75.0% vs 62.1%), for those with a TPS of 1% to 49% (64.0% vs 49.2%), and for patients with a TPS of less than 1% (54.5% vs 32.3%).

No new safety signals were reported with the triplet. Additional data from the study are expected to be presented at a medical meeting in 2025.

“Our level of confidence in efti driving a new standard of care for patients with NSCLC via our pivotal [phase 3] TACTI-004 trial [NCT06726265] continues to rise with the strength of the data from INSIGHT-003 and [the phase 2] TACTI-002 [trial (NCT03625323)],” Marc Voigt, chief executive officer of Immutep, stated in a news release. “Across 2 trials, we have now efficacy data from 165 patients with first-line NSCLC who have been treated with efti and [pembrolizumab], either with or without chemotherapy. In multi-national settings, efti has generated consistent and remarkable improvements in response rates. In particular, the interim ORR data in patients with PD-L1 expression below 50% in the ongoing INSIGHT-003 trial, who represent over two-thirds of the first-line NSCLC patient population, is very encouraging.”

Efti is a first-in-class antigen-presenting cell (APC) activator that binds to MHC class II molecules on APCs. In doing so, efti activates and proliferates of CD8-positive cytotoxic T cells, CD4-positive helper T cells, dendritic cells, natural killer cells, and monocytes. The upregulation of IFN-ƴ and CXCL10 can also further boost the immune system.

INSIGHT is a phase 1 study being conducted in Germany that is evaluating efti in patients at least 18 years of age with advanced solid tumors.2 In INSIGHT-003, patients were required to have locally advanced or metastatic squamous NSCLC who were slated to receive platinum-based chemotherapy plus pembrolizumab and pemetrexed. Key inclusion criteria for stratum C included measurable or assessable disease per RECIST 1.1 criteria; a life expectancy of more than 3 months; an ECOG performance status of 0 or 1; and adequate hematologic, hepatic, renal, and coagulation function.

The study excluded patients with cerebral or leptomeningeal metastases; however, select patients with previously treated brain metastases are allowed to enroll. Patients were also excluded if they had chronic inflammatory bowel disease, active infection requiring systemic therapy, or a history or evidence of interstitial lung disease, active non-infectious pneumonitis, or active tuberculosis.

Patients in stratum C received efti in combination with pembrolizumab, carboplatin, and pemetrexed.1

The feasibility of efti is serving as the primary end point of INSIGHT.2 Secondary end points include safety, ORR, progression-free survival, overall survival, and immune response in whole blood and tumor tissue.

References

1. Immutep’s efti with Keytruda (pembrolizumab) & chemotherapy achieves high response rates in first-line non-small cell lung cancer. News release. Immutep. May 15, 2025. Accessed May 15, 2025. https://www.immutep.com/detail/immutep-s-efti-with-keytruda-r-pembrolizumab-chemotherapy-achieves-high-response-rates-in-first-line-non-small-cell-lung-cancer.html
2. Feasibility and safety of IMP321 (eftilagimod alpha) for advanced stage solid tumors (INSIGHT). ClinicalTrials.gov. Updated February 13, 2025. Accessed May 15, 2025. https://clinicaltrials.gov/study/NCT03252938