First-line Eftilagimod Alpha Plus Pembrolizumab Generates OS Benefit in PD-L1+ NSCLC

Eftilagimod alpha (efti; IMP321) plus pembrolizumab (Keytruda) provided an overall survival (OS) benefit over what has been reported with historical controls when given as first-line treatment in patients with non–small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of at least 1%, according to data from the phase 2 TACTI-002 trial (NCT03625323).¹

Findings showed that PD-L1–positive patients (n = 58) experienced a median OS of 25 months, which compared favorably with historical data from registrational trials of anti–PD-1 monotherapy (median 16.4 months), anti–PD-1 plus chemotherapy (median 15.8 to 23.3 months), and anti–PD-1 plus anti–CTLA-4 (median 17.1 months).

Immutep, the developer of eftilagimod alpha, also reported that the doublet “led to excellent initial survival results in the overall intent-to-treat [ITT]” population with NSCLC who received treatment in the first-line setting, with benefit observed irrespective of PD-L1 status.

“These initial OS results from the TACTI-002 trial are clinically meaningful and build upon the strength of the efficacy data emerging from this exciting novel investigational combination of eftilagimod alpha with pembrolizumab,” Martin Forster, MD, of the UCL Cancer Institute and University College London Hospital NHS Foundation and an investigator on TACTI-002, stated in a news release. “Importantly, the favorable safety profile of this immunotherapy regimen has continued, and to see these deep and durable responses without any additional toxicity from what would be expected from anti–PD-1 monotherapy is very encouraging.”

Eftilagimod alpha is a first-in-class antigen-presenting cell activator that uses 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 non-randomized, open-label, multinational TACTI-002 trial was comprised of 3 parts. Those enrolled to part A (n = 114) had first-line NSCLC unselected for PD-L1, those in part B (n = 36) had second-line NSCLC. That 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 received prior platinum-based treatment.²

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

ORR per RECIST v1.1 criteria served as the trial’s primary end point. Secondary end points included progression-free survival, OS, safety and tolerability, pharmacokinetics, pharmacodynamics, and exploratory biomarkers.

Data from those enrolled to part A were presented at the 2022 SITC Annual Meeting. The median age in this group was 67 years (range, 44-85), and most patients were male (73.7%), had an ECOG performance status of 1 (62.3%), and were current or ex-smokers (94.7%). More than half (63.2%) of patients had nonsquamous disease, and 99.1% had metastatic disease. Regarding previous treatment, 33.3% had radiotherapy, 20.2% underwent surgery, and 22.8% had systemic therapy for nonmetastatic disease.

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

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

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 ranging from 1% to 49% (n = 38), the ORR was 44.7% (95% CI, 28.6%-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 highest, at 55% (95% CI, 31.5%-76.9%), with a median PFS was 16.7 months (95% CI, 4.0-16.8). In those with a TPS of 1% or higher (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 responders 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 that had fatal outcomes. Grade 3 or higher adverse effects (AEs) occurred in 12.3% of patients. Toxicities resulted in treatment discontinuation for 9.6% of patients.

The most common treatment-related AEs 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, the FDA granted fast track designation to eftilagimod alpha for use in combination with pembrolizumab as a frontline treatment in patients with stage IIIB/IV NSCLC with a PD-L1 TPS of at least 1%, based on earlier data from TACTI-002.³

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

References

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