Background

Eftilagimod alpha (E), a soluble LAG-3 protein, acts as an MHC class II agonist triggering activation of antigen-presenting cells (APC) and CD8 T-cells. Stimulating APCs and subsequent T cell recruitment with efti may revert PD-1/PD-L1 resistance. We report updated results from Part B of the TACTI-002 trial: 2^nd line PD-1/PD-L1-resistant non-small cell lung carcinoma (NSCLC) patients (pts) treated with efti plus pembrolizumab (P).

Methods

Pts with metastatic NSCLC unselected for PD-L1 expression and with resistance to 1^st line PD-1/PD-L1 inhibitor-based therapy were enrolled. Primary endpoint (EP) was objective response rate (ORR) by iRECIST. Secondary EPs were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and tolerability. Post-hoc analysis included tumor growth kinetics (TGK). Pts received E (30 mg SC Q2W for eight 3-week cycles and then Q3W up to 1 yr) with P (200 mg IV Q3W up to 2 yrs). Imaging was performed every 9 wks and locally evaluated. PD-L1 TPS was assessed using IHC 22C3 kit.

Results

36 pts enrolled between Apr 2019 – Aug 2021. Median age was 67 yrs (46 – 84) and 61% were male. ECOG PS was 0 and 1 in 33% and 67% of pts. Pts had squamous (19%) and non-squamous (78%) histology. All PD-L1 subgroups were included: 39% with TPS <1% and 82% with TPS <50%. Pts received a PD-1/PD-L1 inhibitor alone (28%) or combined with platinum-based chemo (72%) as 1^st line therapy. Pts received median of 5 (2 – 35) P and 7 (2 – 22) E doses.

ORR and DCR (iRECIST) was 8.3% and 33%. All PRs were confirmed with pts on study 19+ m. TGK analysis was performed on pts with data available on the same lesions from prior failed therapy and post-baseline. Vast majority (83%) of pts showed deceleration (50%) in tumor growth or shrinkage (33%) of target lesions. Median PFS was 2.1 months with PFS rate at 6 m of 25%. 44% were alive at 12 m with median OS of 9.7 m. Most common (>15%) adverse events were decreased appetite (33%), dyspnea (31%), cough (28%), asthenia (22%), fatigue (19%), arthralgia (17%) and weight decreased (17%).

Conclusions

Efti + pembrolizumab is safe and shows encouraging signs of antitumor activity in NSCLC pts resistant to PD-1/PD-L1 inhibitors, warranting further investigation.

Clinical trial identification

2018-001994-25 (EudraCT)
NCT03625323 (ClinicalTrials.gov)