Eftilagimod Alpha Plus Pembrolizumab/Chemo Generates Improved Survival Trends in Advanced NSCLC

Axel Kock – stock.adobe.com

The addition of eftilagimod alpha (efti; IMP321) to pembrolizumab (Keytruda) and chemotherapy led to encouraging overall survival (OS) and progression-free survival (PFS) data compared with historical controls for the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer, according to data from the phase 1 INSIGHT-003 trial (NCT03252938).¹

Findings announced by Immutep showed that at 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) experienced 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

“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,” Salah-Eddin Al-Batran, MD, of the Frankfurt Institute of Clinical Cancer Research (IKF), stated in a news release.¹ “[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.”

The multicenter, investigator-initiated INSIGHT-003 trial enrolled patients at least 18 years of age with histologically confirmed locally advanced or metastatic solid tumors, and stratum C included only patients with NSCLC adenocarcinomas who were slated to receive standard pembrolizumab plus chemotherapy.3 Other key inclusion criteria included an ECOG performance status of 0 or 1; adequate hematological, hepatic and renal function; evidence of measurable disease or assessable disease per RECIST 1.1 criteria; and a life expectancy of more than 3 months.

Patients with NSCLC received carboplatin at area under the curve 5 plus pemetrexed at 500 mg/m2 once every 3 weeks for 4 cycles, followed by optional pemetrexed maintenance at 500 mg/m2 once every 3 weeks, in combination with pembrolizumab at 200 mg once every 3 weeks and efti at 30 mg once every 2 weeks for 24 weeks, then once every 3 weeks until week 52.⁴

The primary end point was the feasibility of treatment, looking specifically at safety and tolerability. Secondary end points included OS, PFS, and overall response rate (ORR).⁴

Additional data from all evaluable patients (n = 40) showed that efti plus pembrolizumab and chemotherapy produced an ORR of 55.0% and a disease control rate of 87.5%.¹ The ORR was 75.0% in patients with a PD-L1 tumor proportion score (TPS) of more than 50% (n = 4); 58.8% in patients with a PD-L1 TPS of 1% to 49% (n = 17); and 47.4% in patients with a PD-L1 TPS of less than 1% (n = 19).

No new safety signals were reported for 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,” Marc Voigt, CEO of Immutep, added in a news release.¹ “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.”

References

1. Immutep’s efti 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://www.immutep.com/detail/immutep-s-efti-shows-excellent-survival-data-from-insight-003-trial-in-non-small-cell-lung-cancer.html
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
4. Atmaca A, Müller DW, Habibzada T, et al. INSIGHT 003 evaluating feasibility of eftilagimod alpha (soluble LAG-3) combined with first-line chemo-immunotherapy in metastatic non-small cell lung cancer (NSCLC) adenocarcinomas. Ann Oncol. 2023;34(suppl 2):S632. doi:10.1016/j.annonc.2023.09.2181