First-Line Eftilagimod Alpha Plus Pembrolizumab Generates OS Benefits in PD-L1+ NSCLC

Eftilagimod alfa (efti; IMP321) plus pembrolizumab (Keytruda) provided overall survival (OS) benefit compared with historical controls when given as first-line treatment in patients with non-small cell lung cancer (NSCLC) and PD-L1 tumor proportion score (TPS) of at least 1%, according to data from the Phase 2 study TACTI-002 (NCT03625323).¹

Results showed that PD-L1 positive patients (n = 58) had a median OS of 25 months, which compares favorably with historical data from pivotal trials of antiPD-1 monotherapy (median 16.4 months), antiPD-1 plus chemotherapy (median 15.8 to 23.3 months) and antiPD-1 plus antiCTLA-4 (median 17.1 months).

Immutep, the developer of eftilagimod alfa, also reported that the doublet led to excellent initial survival outcomes in overall treatment intent [ITT] NSCLC population receiving first-line treatment, with observed benefit regardless of PD-L1 status.

These initial OS results from the TACTI-002 study are clinically meaningful and build on the strength of efficacy data emerging from this exciting new investigational combination of eftilagimod alfa with pembrolizumab, Martin Forster, MD, UCL Cancer Institute and University College London Hospital NHS Foundation and an investigator on TACTI-002, said in a press release. Importantly, the favorable safety profile of this immunotherapy regimen has continued and to see these profound and long-lasting responses without any additional toxicity compared to what would be expected from antiPD-1 monotherapy is very encouraging.

Eftilagimod alfa is a first-in-class antigen-presenting cell activator that utilizes the unique characteristics of LAG-3 to activate both innate and adaptive immunity by binding to CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells and monocytes.

The multinational, non-randomised, open-label study TACTI-002 consisted of 3 parts. Those enrolled in Part A (n = 114) had first-line NSCLC not screened for PD-L1, those in Part B (n = 36) had second-line NSCLC. This was resistant to PD-1/L1-based therapy, and Part C (n = 39) included those with second-line head and neck squamous cell carcinoma who had received prior platinum-based treatment.²

Those in Part A received 30 mg of eftilagimod alfa via subcutaneous injection every 2 weeks for the first 8 cycles, then every 3 weeks starting with cycle 9, plus 200 mg of intravenous pembrolizumab every 3 weeks for up to 2 years.

The ORR criteria for RECIST v1.1 served as the primary endpoint of the studies. Secondary endpoints included progression-free survival, OS, safety and tolerability, pharmacokinetics, pharmacodynamics, and exploratory biomarkers.

Data from Part A enrollees were presented at the 2022 SITC Annual Meeting. The mean age in this group was 67 years (range 44-85), and the majority of patients were male (73.7%). had an ECOG performance status of 1 (62.3%) and were current or former smokers (94.7%). More than half (63.2%) of patients had nonsquamous disease and 99.1% had metastatic disease. Regarding prior treatment, 33.3% received radiotherapy, 20.2% underwent surgery, and 22.8% received systemic therapy for non-metastatic disease.

According to central testing alone, 35.6% of patients had a PD-L1 TPS of less than 1%, 42.2% had a TPS between 1% and 49%, and 22.2% had a TPS of 50% or higher. According to central and local tests, these rates were 34.3%, 38.9%, and 26.9%, respectively.

At the time of presentation, the doublet elicited an overall response rate (ORR) of 38.6% (95% CI, 29.6%-48.2%) according to RECIST v1.1 criteria, which included a rate of complete response rate of 0.9% and partial response rate response rate of 37.8%; 32.5% of patients had stable disease, 17.5% experienced disease progression, and 11.4% were not evaluable for response.

By iRECIST criteria, the ORR with the combination was 40.4% (95% CI, 31.3%-50.0%) in the ITT population. In those with a TPS of less than 1% (n = 32), the ORR with the regimen was 31.3% (95% CI, 16.1%-50.0%) and the median PFS was 4 .2 months (95% CI, 3.6-6.1 ). In the group with a TPS of 1% to 49% (n = 38), the ORR was 44.7% (95% CI, 28.6% to 61.7%) and the median PFS was 8. 3 months (95% CI, 4.4-15.7).

In those with a PD-L1 TPS of at least 50% (n = 20), the ORR was higher, at 55% (95% CI, 31.5%-76.9%), with a median PFS of 16.7 months (95% CI, 4.0-16.8). In those with a TPS of 1% or greater (n = 58), the ORR was 48.3% (95% CI, 35.0%-61.8%) and the median PFS was 9.3 months (95% CI, 6.1-15.7).

The median duration of response in 40 evaluable patients was a median of 21.6 months (95% CI, 17.3-30.0).

Regarding safety, serious toxicities were experienced by 10.5% of patients and 2.6% experienced events with a fatal outcome. Grade 3 or higher adverse effects (AEs) occurred in 12.3% of patients. Toxicities led to treatment discontinuation for 9.6% of patients.

The most common treatment-related adverse events experienced by at least 10% of patients included pruritus (any grade, 20.2%), asthenia (any grade, 19.3%), rash (any grade, 13.2%). diarrhea (any grade, 10.5%; grade 3, 0.9%), and fatigue (any grade, 10.5%, grade 3, 0.9%).

In October 2022, FDA granted accelerated designation to eftilagimod alfa for use in combination with pembrolizumab as first-line treatment in patients with stage IIIB/IV NSCLC with a PD-L1 TPS of at least 1%, based on previous data from TACTI-002.³

More mature OS data and additional safety and efficacy findings are slated for presentation at an upcoming physician meeting in 2023.¹

References

1. Immuteps efti in combination with pembrolizumab achieves an excellent overall survival lead in first-line non-small cell lung cancer. Press release. immutep. May 17, 2023. Accessed May 17, 2023. https://www.immutep.com/detail/2023
2. Iams W, Felip E, Majem M, et al. Combination of eftilagimod antigen-presenting cell activator alfa (soluble LAG-3) and pembrolizumab: efficacy results from the non-small cell lung cancer first-line cohort of TACTI-002 (phase II). Presented at the SITC 2022 Annual Meeting; 8-12 November 2022; Boston, Mass. Retrieved 1470. https://www.immutep.com/files/content/investor/presentation/2022/SITC%202022/TACTI-002_SITC%202022_Poster_final.pdf
3. Immutep receives FDA accelerated designation for LAG-3 therapeutic eftilagimod alpha for first-line non-small cell lung cancer. Press release. immutep. October 4, 2022. Accessed May 17, 2023. https://www.immutep.com/detail/immutep-receives-fda-fast-track