Eftilagimod Alpha Combo Shows Promise in First-Line NSCLC

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In the phase 1 INSIGHT-003 trial (NCT03252938), the combination of eftilagimod alpha (efti; IMP321), pembrolizumab (Keytruda), and chemotherapy showed promising results in terms of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC).¹

With a minimum follow-up of 22 months, patients treated with the combination (n = 21) experienced a median OS of 32.9 months and a median PFS of 12.7 months. The 24-month OS rate was 81.0%. In contrast, historical data from the phase 3 KEYNOTE-189 trial (NCT02578680) showed that at a median follow-up of 23.1 months, patients treated with 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 evaluable patients (n = 40), the combination of efti, pembrolizumab, and chemotherapy led to an ORR of 55.0% and a disease control rate of 87.5%.¹ 

“The strength of these mature survival results coupled with a favorable safety profile in first-line treatment of patients with nonsquamous NSCLC, the vast majority of whom have negative or low PD-L1 expression, is very encouraging,” said Salah-Eddin Al-Batran, MD, of the Frankfurt Institute of Clinical Cancer Research (IKF), in a press release. “[These] promising data in INSIGHT-003 suggest a complementary effect from the addition of efti, a unique MHC class II agonist, to the standard-of-care combination of pembrolizumab and chemotherapy, which has revolutionized the treatment landscape in lung cancer.”

In patients with a PD-L1 tumor proportion score (TPS) of more than 50% (n = 4), the ORR was 75.0%. For those with a PD-L1 TPS of 1% to 49% (n = 17), the ORR was 58.8%. Further, the ORR was 47.4% among those with a PD-L1 TPS of less than 1% (n = 19).

Safety findings showed that there were no new safety signals observed with the combination.

“The OS and PFS data from this mature cohort of patients in INSIGHT-003 with nearly a 2-year minimum follow-up exceeds our expectations. We are encouraged to see efti build upon the historical clinical outcomes from the most widely used immunotherapy-chemotherapy combination today,” said Marc Voigt, chief executive officer of Immutep, in a news release.

“Additionally, the early evaluations in the expansion cohort of 19 patients, who all have low or negative PD-L1 expression, are tracking well, and we look forward to additional data updates from the INSIGHT-003 trial in 2025 and beyond. Our focus on potentially driving a new standard of care globally in first line treatment of NSCLC is boosted by these results and we are well advanced in our preparations to initiate the [phase 3] TACTI-004 trial,” added Voigt.

Additional updates from the trial are expected in 2025.

About INSIGHT-003

INSIGHT-003 is a multicenter, investigator-initiated trial evaluating efti, pembrolizumab, and chemotherapy in patients 18 years of age or older with histologically confirmed locally advanced or metastatic solid tumors.³ Stratum C included patients with NSCLC adenocarcinomas who were slated to receive standard pembrolizumab plus chemotherapy.

Enrollment in the study was also open to patients with an ECOG performance status of 0 or 1, and patients were required to have adequate hematological, hepatic and renal function and evidence of measurable disease or assessable disease per RECIST 1.1 criteria. Moreover, patients must have had a life expectancy of 3 months or more.

The primary end point was the feasibility rate of treatment. 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

1. Immutep’sefti shows excellent survival data from INSIGHT-003 trial in non-small cell lung cancer. News release. Immutep. November 14, 2024. Accessed November 14, 2024. https://tinyurl.com/yc5vter3

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. ClinicalTrials.gov. Updated November 7, 2024. Accessed November 14, 2024. https://clinicaltrials.gov/study/NCT03252938