Reference Detail

Ref Type

Journal Article

PMID

(38995265)

Authors

Forster M, Brana I, Pousa AL, Doger B, Roxburgh P, Bajaj P, Peguero J, Krebs M, Carcereny E, Patel G, Mueller C, Brignone C, Triebel F

Title

Eftilagimod Alpha (Soluble LAG3 Protein) Combined with Pembrolizumab as Second-Line Therapy for Patients with Metastatic Head and Neck Squamous Cell Carcinoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	30	17	2024 Sep 03	3726-3734	Clin Cancer Res

URL

Abstract Text

Eftilagimod alpha (efti), a soluble LAG3 protein, activates antigen-presenting cells (APC) and downstream T cells. TACTI-002 (part C) evaluated whether combining efti with pembrolizumab led to strong antitumor responses in patients with second-line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) while demonstrating good tolerability.In this multinational phase II trial using Simon's two-stage design, patients who were PD-L(1)-naïve with R/M HNSCC who had failed first-line platinum-based therapy, unselected for PD-L1, received intravenous pembrolizumab (200 mg, once every 2 weeks) combined with subcutaneous efti (30 mg once every 2 weeks for 24 weeks and once every 3 weeks thereafter). The primary endpoint was objective response rate per RECIST 1.1 modified for immune-based therapy by investigator assessment. Additional endpoints included duration of response, progression-free survival, overall survival, and tolerability. Pharmacodynamic effects (absolute lymphocyte count) and Th1 cytokine biomarkers (IFNγ/CXCL10)] were evaluated in liquid biopsies.Between March 2019 and January 2021, 39 patients were enrolled; 37 were evaluated for response. All patients received prior chemotherapy, and 40.5% were pretreated with cetuximab; 53.1% of patients had PD-L1 combined positive score <20. With a median follow-up of 38.8 months, the objective response rate was 29.7%, including 13.5% complete responders. The median duration of response was not reached. Rapid and sustained absolute lymphocyte count increase was observed in patients who had an objective response. Th1 biomarkers increased sustainably after first treatment. No unexpected safety signals were observed.Efti plus pembrolizumab was safe and showed encouraging antitumor activity and pharmacodynamic effects in patients with second-line head and neck squamous cell carcinoma (HNSCC), thus supporting further evaluation of this combination in earlier treatment lines.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 over exp	head and neck squamous cell carcinoma	predicted - sensitive	Eftilagimod alpha + Pembrolizumab	Phase II	Actionable	In a Phase II trial, Eftilagimod alpha (IMP321) and Keytruda (pembrolizumab) combination therapy resulted in an objective response rate (ORR) of 29.7% (11/37) and disease control rate (DCR) of 37.8% in patients with recurrent or metastatic head and neck squamous cell carcinoma, with an ORR of 60% (9/15), median progression-free survival of 13.6 months, and a median overall survival of 15.5 months in patients with high CD274 expression (PD-L1; CPS>/=20) (PMID: 38995265; NCT03625323).	38995265