The addition of eftilagimod alpha (efti; IMP321) to pembrolizumab (Keytruda) and chemotherapy has shown 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 (NSCLC). These findings come from the phase 1 INSIGHT-003 trial (NCT03252938). The results suggest a potential new approach to improving outcomes in this challenging patient population.
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%. These results were announced by Immutep, the developer of eftilagimod alpha.
Comparison with Historical Data
Historical data from the phase 3 KEYNOTE-189 trial (NCT02578680) showed that 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) at a median follow-up of 23.1 months. This comparison highlights the potential benefit of adding eftilagimod alpha to the standard treatment regimen.
Expert Commentary
Salah-Eddin Al-Batran, MD, of the Frankfurt Institute of Clinical Cancer Research (IKF), stated, "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. [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."
Trial Design and Patient Population
The multicenter, investigator-initiated INSIGHT-003 trial enrolled patients at least 18 years of age with histologically confirmed locally advanced or metastatic solid tumors. Stratum C included only patients with NSCLC adenocarcinomas who were slated to receive standard pembrolizumab plus chemotherapy. 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.
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).
Additional Efficacy Data
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%. 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).
Safety Profile
No new safety signals were reported for the combination, indicating that the addition of eftilagimod alpha did not significantly increase the toxicity of the pembrolizumab and chemotherapy regimen.
Implications and Future Directions
Marc Voigt, CEO of Immutep, added, "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. 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."
