Eftilagimod Alfa Combo Appears Efficacious in Head and Neck Cancer

"The clinically meaningful response rate and high unmet medical need warrant further investigation of eftilagimod plus pembrolizumab in this patient population," according to Robert Metcalf, MD, PhD.

First-in-class antigen presenting cell (APC) activator, eftilagimod alfa (Efti), in combination with pembrolizumab (Keytruda), achieved high efficacy and a favorable safety profile for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with negative PD-L1 expression, according to a news release on cohort B findings from the phase 2b TACTI-003 trial (NCT04811027).¹

Topline data revealed an objective response (ORR) rate of 35.5% in the combination arm. Additionally, the disease control rate (DCR) was 58.1%. Compared with previous chemotherapy-free approaches in PD-L1–negative disease, these findings exceeded historical anti–PD-1 monotherapy control rates of 5.4% for ORR and 32.4% for DCR.

"The high response rate from this novel immunotherapy combination is well above other treatment approaches without chemotherapy. It matches historical response rates from chemotherapy-based treatments but without the associated toxicities,” Robert Metcalf, MD, PhD, medical oncologist and clinician of the Christie NHS Foundation Trust in Manchester, United Kingdom, stated in a news release on the results of the treatment.¹ “The clinically meaningful response rate and high unmet medical need warrant further investigation of eftilagimod plus pembrolizumab in this patient population."

The ongoing phase 2b TACTI-003 trial had 31 evaluable PD-L1–negative patients for the final analysis set. The study consists of 2 cohorts; cohort A is comparing eftilagimod plus pembrolizumab with pembrolizumab monotherapy in patients with PD-L1–positive tumors, and cohort B is assessing the combination therapy in PD-L1–negative tumors.

In cohort A, patients in the experimental arm received 30 mg of eftilagimod bi-weekly for 4 6-week cycles and then every 3 weeks for up to 18 6-week cycles.² This population also received 400 mg of pembrolizumab every 6 weeks for 18 6-week cycles. Patients in the monotherapy arm received the same dosing regimen of pembrolizumab as the experimental arm.

Patients in cohort B received the same dosing regimen as the experimental arm in cohort A.

The primary end point of the study is ORR. Secondary end points include overall survival (OS), progression-free survival (PFS), and duration of response (DOR).

A complete response was observed in 9.7% (n = 3/31) of patients, an improvement when compared with a rate of 0% in a historical control population who received anti–PD-1 monotherapy in first-line HNSCC. Additionally, a patient with early progressive disease gained a partial response with treatment and remains on therapy after 14 months.

Over 50% of those in cohort B received treatment for 6 or more months as of the data cutoff date of March 11, 2024. The combination therapy yielded no new safety signals and currently holds a favorable safety profile.

Inclusion criteria included patients with histologically or cytologically confirmed recurrent disease not amenable to treatment with local or systemic therapy, or metastatic HNSCC considered incurable with local therapies, and an ECOG performance status of 0 or 1. Additional criteria included availability of tissue for PD-L1 biomarker analysis, availability of PD-L1 biomarker results by using Dako standardized diagnostic test, and availability of tissue for testing of human papillomavirus (HPV) status for oropharyngeal cancer.

Main exclusion criteria included patients with disease suitable for local therapy, previous treatment with 1 or more systemic regimens for recurrent and/or metastatic disease, patients with histologically or cytologically confirmed head and neck cancer of any other anatomic location not specified in inclusion criteria, and patients with progressive disease within 6 months of completing curatively intended systemic treatment for locally or locoregionally advanced HNSCC.

References

1. Immutep reports positive results in first line head and neck squamous cell carcinoma patients with negative PD-L1 expression. News release. Immutep Ltd. July 12, 2024. Accessed July 12, 2024. https://tinyurl.com/yj7vvezt
2. 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 July 3, 2024. Accessed July 12, 2024. https://clinicaltrials.gov/study/NCT04811027