359 Results from a phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic 2nd line head and neck squamous cell carcinoma (HNSCC)

Abstract

BackgroundEftilagimod alpha (efti) is a soluble LAG-3 protein targeting a subset of MHC class II, thus mediating antigen presenting cell (APC) and CD8 T-cell activation. Such stimulation of the dendritic cell network and resulting T cell recruitment by efti may lead to stronger anti-tumor responses than observed with pembrolizumab alone. We hereby report results of the 2nd line metastatic head and neck squamous cell carcinoma (HNSCC) cohort (part C) of the TACTI-002 phase II trial (NCT03625323).MethodsEligible patients (pts) with HNSCC, unselected for PD-L1 expression with disease progression on or after 1st line platinum-based therapy, received 30 mg subcutaneous efti Q2W for 24 weeks and 200 mg pembrolizumab Q3W for up to 2 years or until disease progression. The study used a Simon’s 2-stage design with objective response rate (ORR) as the primary endpoint (EP). Secondary EPs included tolerability, progression free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics, and immunogenicity. Tumor response was assessed Q9W. PD-L1 was assessed centrally (22C3 clone). The study was approved by ethic committees and institutional review boards.ResultsBetween Mar 2019 and Jan 2021, 39 pts were enrolled (cut-off Apr 2021). The median age was 62 yrs (range 37–84) with 90% male pts. ECOG was 0 and 1 in 33% and 67%, respectively. Primary tumor location at diagnosis was oropharynx (36%), oral cavity (31%), hypopharynx (18%) and larynx (15%) with all PD-L1 subgroups (CPS< 1, ≥1 to ≤19; ≥20) being represented. All pts were pre-treated with platinum-based chemotherapy. Thirty-seven (37) pts were evaluated for response with ORR (iRECIST) of 30% (95% CI 16–47%) with 5 (14%) CRs; 6 (16%) PRs; 3 (8%) SDs; 17 (46%) PDs and 6 (16%) pts not evaluable. Median PFS was 2.1 months and 30+% were progression-free at 6 months. One patient (3%) discontinued due to pembro-related adverse event. The most common (>10%) treatment emergent adverse events were hypothyroidism (21%), cough (18%), asthenia (15%), fatigue (13%), anemia (13%), diarrhea (13%) and weight decreased (13%).ConclusionsEfti in combination with pembrolizumab is safe, showing encouraging antitumor activity in platinum pre-treated, 2nd line HNSCC patients. For further investigation of this combination, a 1st line HNSCC trial (NCT04811027) has been initiated.Trial RegistrationNCT03625323Ethics ApprovalThe study was approved by relevant ethic committees and institutional review boards

A soluble LAG-3 protein (eftilagimod alpha) and an anti-PD-L1 antibody (avelumab) tested in a phase I trial: a new combination in immuno-oncology

“…This is in line with previous results showing no added safety signals in terms of immune-related AEs for the combination of 30-mg s.c. administered efti with the ICI pembrolizumab in HNSCC and NSCLC. 23 , 26 Thus efti can be safely administered at 30 mg s.c. administered in combination with an anti-PD-L1 agent, such as avelumab.…”

“…The results of second-line treatment of head and neck squamous cell carcinoma (HNSCC) showed a 30% objective response rate (ORR; iRECIST) with the combination of 30 mg s.c. administered efti compared with 15% observed for pembrolizumab monotherapy in the overall population of the KEYNOTE-040 trial. 22 , 23 In addition, TACTI-002, evaluating the combination of efti plus pembrolizumab as first-line therapy in patients with metastatic non-small-cell lung cancer (NSCLC), demonstrated an increased ORR of the combination with 30 mg s.c. administered efti (48%) compared with the historical data of pembrolizumab monotherapy in the KEYNOTE-042 trial (ORR 27%) for patients with PD-L1 tumor proportion score ≥1%. Here, the benefit of efti addition was even more pronounced in the subpopulation with low PD-L1-expressing tumors (tumor proportion score 1%-49%), with an ORR of 45% in TACTI-002 versus 17% in KEYNOTE-042.…”