Eftilagimod Alpha Plus Pembrolizumab Elicits Early Efficacy Signals in Metastatic HNSCC

Frontline eftilagimod alpha plus pembrolizumab (Keytruda) generated responses in patients with recurrent or metastatic head and neck squamous cell carcinoma patients (HNSCC) with negative PD-L1 expression, according to preliminary topline findings from cohort B of the phase 2b KEYNOTE-PNC-34/TACTI-003 trial (NCT04811027).¹

Findings from TACTI-003 demonstrated that the combination produced a 26.9% overall response rate (ORR) and a disease control rate (DCR) of 57.7% per RECIST v1.1 criteria in patients with tumors with a PD-L1 combined positive score (CPS) of less than 1 (n = 26). Cohort B has enrolled a total of 33 patients; these findings are from the 26 patients with currently available data with adequate follow-up at the February 2024 data cutoff. Immutep Limited noted that the final number of efficacy-evaluable patients is expected to be higher and that additional data from cohort B will be released together with those from cohort A in the first half of 2024.

“These preliminary topline results in the first-line setting for patients with HNSCCs that do not express PD-L1 are encouraging,” Martin Forster, of the University College London (UCL) Cancer Institute and UCL Hospital NHS Foundation in England, said in a press release. “HNSCCs are a heterogeneous disease that represent a high unmet medical need regardless of PD-L1 expression. This is especially the case for patients with tumors that do not express PD-L1 and those that cannot receive chemotherapy. The ability of Eftilagimod alpha to work with [the] anti–PD-1 therapy [pembrolizumab] to potentially improve patients’ clinical responses and expand patient populations that respond to the latter, without using chemotherapy, is promising.”

Eftilagimod alpha is a soluble LAG-3 protein and major histocompatibility complex (MHC) class II agonist that is a first-in-class antigen-presenting cell activator. The agent stimulates both innate and adaptive immunity by binding to MHC class II molecules on antigen-presenting cells, leading to activation and proliferation of CD8-positive cytotoxic T cells, CD4-positive helper T cells, dendritic cells, natural killer cells, and monocytes.

TACTI-003 is an ongoing multicenter, open-label study that is enrolling patients with metastatic or recurrent HNSCC in the first-line setting. Eligible patients must have available tissue for PD-L1 biomarker analysis, available tissue for testing of human papillomavirus, and an ECOG performance status of 1 or 0. Patients are divided into 2 cohorts: patients in cohort A need to have a PD-L1 CPS of 1 or greater, and those in cohort B must have a PD-L1 CPS of less than 1.²

Patients in cohort A will be randomly assigned 1:1 to receive eftilagimod alpha plus pembrolizumab or pembrolizumab monotherapy. Those in cohort B received the combination regimen. Subcutaneous eftilagimod alpha will be given for up to 24 months at a dose of 30 mg every 2 or 3 weeks. Intravenous pembrolizumab at 400 mg will be administered every 6 weeks for up to 24 months.² The primary analysis of the study will be conducted following the completion of at least 3 cycles of treatment totaling 18 weeks or trial discontinuation.¹

The primary end point is ORR per RECIST v1.1 criteria. Secondary end points included DCR, overall survival, time to response, duration of response, progression-free survival, and safety. PD-L1 expression and biomarker evaluation represent exploratory end points.²

Eftilagimod alpha is currently being investigated in other solid tumors, including non-small cell lung cancer and metastatic breast cancer. In April 2021, the agent received fast track designation from the FDA for the frontline treatment of patients with recurrent or metastatic HNSCC.³

References

• Immutep announces positive preliminary topline results from TACTI-003 cohort B. News release. Immutep Limited. April 24, 2024. Accessed April 24, 2024. https://www.immutep.com/detail/immutep-announces-positive-preliminary-topline-results-from-tacti-003-cohort-b.html
• Combination study with eftilagimod alpha (a soluble LAG-3 fusion protein) and pembrolizumab in patients with recurrent or metastatic HNSCC (TACTI-003). ClinicalTrials.gov. Updated November 13, 2023. Accessed April 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04811027
• Immutep achieves fast track designation from US FDA for Efti, a soluble LAG-3 protein, in first line recurrent/metastatic head & neck cancer. News release. Immutep Limited. April 8, 2021. Accessed April 24, 2024. https://www.immutep.com/files/content/investor/press-release/2021/Immutep%20Achieves%20Fast%20Track%20designation%20for%20Efti%20from%20US%20FDA%20-%208Apr2021.pdf