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

Eftilagimod alpha plus pembrolizumb and chemotherapy generated favorable survival data in nonsquamous NSCLC.

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