Immutep Limited announced positive data from the INSIGHT-003 Phase I trial, evaluating eftilagimod alpha (efti) in combination with pembrolizumab and chemotherapy for first-line treatment of metastatic non-squamous non-small cell lung cancer (NSCLC). The data, with a minimum follow-up of 22 months, demonstrates encouraging survival benefits and a favorable safety profile.
Key Survival Outcomes
The INSIGHT-003 trial reported a median overall survival (OS) of 32.9 months, a median progression-free survival (PFS) of 12.7 months, and a 24-month overall survival rate of 81.0% in patients treated with the triple combination therapy. These results compare favorably to historical data from a registrational trial of anti-PD-1 therapy and doublet chemotherapy, which showed a median OS of 22.0 months, a median PFS of 9.0 months, and a 24-month OS rate of 45.5% in a similar patient population.
Prof. Dr. Salah-Eddin Al-Batran of the Frankfurt Institute of Clinical Cancer Research (IKF) noted, "The strength of these mature survival results coupled with a favourable safety profile in first-line treatment of patients with non-squamous NSCLC, the vast majority of whom have negative or low PD-L1 expression, is very encouraging."
Overall Response Rate
Data from all evaluable patients (N=40) showed an improved overall response rate (ORR) across all levels of PD-L1 expression compared to historical controls:
- 75.0% ORR versus 62.1% ORR in patients with high PD-L1 expression (TPS >50%)
- 58.8% ORR versus 49.2% ORR in patients with low PD-L1 expression (TPS 1-49%)
- 47.4% ORR versus 32.3% ORR in patients with negative PD-L1 expression (TPS <1%)
In patients with low and negative PD-L1 expression (36 of 40 patients), the triple combination achieved a 52.8% ORR and 86.1% Disease Control Rate (DCR).
Safety Profile
The combination of efti, pembrolizumab, and chemotherapy continues to demonstrate a favorable safety profile, with no new safety signals reported.
Future Directions
The INSIGHT-003 trial is nearing completion of patient enrolment, and additional data updates are expected in 2025 and beyond. Immutep is also advancing preparations for the TACTI-004 Phase III trial, building on the promising results from INSIGHT-003.
Marc Voigt, CEO of Immutep, stated, "We are encouraged to see efti build upon the historical clinical outcomes from the most widely used immunotherapy-chemo combination today... Our focus on potentially driving a new standard of care globally in first line treatment of NSCLC is boosted by these results."
