In January, the Saudi Arabia Food and Drug Authority (SFDA) announced the accelerated approval of nogapendekin alfa inbakicept-pmln, in combination with immune checkpoint inhibitors (ICIs), for the treatment of metastatic non-small cell lung cancer (NSCLC) after disease progression on standard-of-care (SOC) treatment.1
The decision is supported by data from the phase III QUILT-2.023 trial and the phase 2b QUILT-3.055 trial, in which nogapendekin alfa plus ICI therapy demonstrated immune restoration and overall survival (OS) benefits.2 Both trials were designed to test the hypothesis that disease recurrence after ICI reflects immune exhaustion and lymphocyte depletion.2 They also evaluated whether activation of natural killer cells and CD8+ T cells with alfa inbakicept-pmln plus ICIs could restore immune competence and improve outcomes.2
The QUILT-2.023 trial evaluated the combination as a first-line treatment for patients with advanced or metastatic NSCLC.2 According to previously reported data, the nogapendekin alfa-ICI regimen produced a statistically significant and sustained improvement in absolute lymphocyte counts (ALCs) versus ICI alone.1 The primary randomized cohort enrolled patients with stage III or IV squamous or nonsquamous NSCLC who had PD-L1 expression of 1% or higher and had not received prior systemic therapy for advanced disease. Patients were randomly assigned 1:1 to receive either ICI alone or ICI plus nogapendekin alfa inbakicept-pmln.2
In the QUILT-3.055 trial, nogapendekin alfa plus ICIs restored or maintained an ALC of 1.0 x 103 cells/µL or higher in 77% of enrolled patients with second- or later-line NSCLC.1 The enrolled patients were heavily pretreated and received the same ICI with which they had previously responded or stabilized, alongside subcutaneous administration of nogapendekin alfa inbakicept-pmln in repeated 6-week cycles.2
The combination regimen also demonstrated OS benefits among patients treated with nogapendekin alfa inbakicept-pmln plus ICI, with a median OS of 16.2 months, compared to 11.8 months in those who did not.1 Additionally, patients who achieved higher immune competence (ALC ≥ 1.2 ×103 cells/µL), demonstrated a greater survival benefit (median OS: 21.1 months) regardless of PD-L1 status. This surpasses historical median OS values of 7–9 months with SOC chemotherapy.1
The clinically meaningful benefits of nogapendekin alfa inbakicept-pmln combined with ICI represent a potential paradigm shift for patients with NSCLC who have exhausted standard treatment options. A randomized phase III confirmatory trial is in progress to compare nogapendekin alfa inbakicept-pmln plus ICI versus docetaxel as a second-line treatment for NSCLC.2
References
- 1. Nogapendekin Alfa Combo Earns Approval in Saudi Arabia for Metastatic NSCLC. http://bit.ly/3Z99bSW
- 2. ImmunityBio announces positive results demonstrating ANKTIVA as a lymphocyte stimulating agent in combination with checkpoint inhibitors in non-small cell lung cancer. https://tinyurl.com/eauukmpx
