Treatment with eftilagimod alpha in combination with pembrolizumab appears safe and well tolerated among patients with metastatic head and neck squamous cell carcinoma in the phase 2 TACTI-002 study.
The soluble LAG-3 protein eftilagimod alpha plus pembrolizumab (Keytruda) demonstrated encouraging responses and was well tolerated in patients with metastatic head and neck squamous cell carcinoma (HNSCC), according to findings from part C of the phase 2 TACTI-002 study (NCT03625323) that were presented at a poster session during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
The study regimen produced an objective response rate (ORR) of 29.7% (95% CI, 15.9%-47.0%) in the intent-to-treat (ITT) population. Investigators also reported complete responses (CRs) in 13.5% and partial responses (PRs) in 16.2% by iRECIST criteria. The ORR was 35.5% (95% CI, 19.2%-54.6%) in the evaluable population per immune RECIST criteria. Additionally, investigators confirmed responses in 91% of patients, including a confirmed ORR of 27.0% (95% CI, 13.8%-44.1%) in the ITT population. The median response onset was 1.9 months, and less than 10% of patients with responses had disease progression within 6 months.
Eftilagimod alpha plus pembrolizumab yielded a median progression-free survival (PFS) of 2.1 months (95% CI, 2.0-4.3) and a median overall survival (OS) of 8.7 months (95% CI, 4.8-15.6). The 6-month PFS rate was 32.4%, and the 12-month OS rate was 46.0%.
The median duration of response (DOR) was not reached with 4 events (40%) at a median follow-up of 38.8 months. Additionally, the 12-month and 24-month DOR rates, respectively, were 80.0% and 60.0% in the ITT population.
In part C of the non-randomized, international, open-label phase 2 TACTI-002 trial, investigators assessed eftilagimod alpha plus pembrolizumab in the treatment of those with second-line HNSCC unselected for PD-L1 expression. A total of 39 patients enrolled on the trial. Patients received 30 mg of eftilagimod alpha subcutaneously once every 2 weeks for the first 8 cycles and once every 3 weeks in the following 9 cycles plus 200 mg of pembrolizumab intravenously every 3 weeks for up to 2 years.
The primary end point of the trial was ORR based on iRECIST criteria. Secondary end points included PFS, OS, safety and tolerability, and pharmacokinetics.
Investigators centrally assessed tumor cell PD-L1 expression retrospectively.
Patients with advanced or metastatic recurrent HNSCC in the oral cavity, oropharynx, hypopharynx, or larynx were eligible for enrollment on the study. Patients also needed to have disease progression following first-line platinum-based treatment to enroll.
Patients had a median age of 63 years (range, 48-84). Most patients were male (89.2%) and had an ECOG performance status of 1 (64.9%). Additionally, most had a primary tumor located in the oropharynx (35.1%), metastatic disease (91.9%), and a PD-L1 combined positive score (CPS) of at least 1 (78.1%).
Treatment lasted for a median duration of 2.7 months (range, 0.02-12.9) with both eftilagimod alpha and pembrolizumab (range, 0.02-24.6). Additionally, 4 patients completed at least 2 years of treatment, and 33 discontinued treatment, with the most common reasons including death (18.2%), disease progression (57.6%), adverse effects (AEs; 15.2%), and patient withdrawal (3.0%).
Among patients with a PD-L1 CPS of at least 20 (n = 15), below 20 (n = 17), and 1 or higher (n = 25), respectively, the ORR was 60.0% (95% CI, 32.3%-83.7%), 11.8% (95% CI, 1.5%-36.4%), and 38.5% (95% CI, 20.2%-59.4%). The median PFS in each group was 13.6 months (95% CI, 1.6-24.8), 2.0 months (95% CI, 1.3-2.7), and 2.3 months (95% CI, 1.6-13.6), and the corresponding 6-month rates were 53.3%, 17.7%, and 40.0%. Additionally, the median OS in each respective group was 15.5 months (95% CI, 4.9-31.1), 7.5 months (95% CI, 1.9-18.8), and 12.6 months (95% CI, 4.8-24.8), with 12-month OS rates of 66.7%, 35.3%, and 52.0%.
The median DOR was not reached in the CPS of at least 20 group, 16.2 months in the below 20 group, and not reached in the 1 or higher group. In each respective group, the 12-month DOR rates were 87.5%, 50.0%, and 77.8%, and the 24-month rates were 62.5%, 50.0%, and 55.6%.
Overall, no patients died due to treatment-related AEs, and 7.7% experienced serious AEs. Additionally, 12.8% had grade 3 or higher AEs, and 5.1% had AEs leading to treatment discontinuation. The most common any-grade AEs related to study treatment included hypothyroidism (20.5%), pruritus (10.3%), and fatigue (10.3%). Investigators also reported 1 instance of grade 3 hypothyroidism.
de Spéville BD, Felip E, Forster M, et al. Final results from TACTI-002 Part C: A phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with metastatic 2nd line head and neck squamous cell carcinoma unselected for PD-L1. J Clin Oncol. 2023;41(suppl 16):6029. doi:10.1200/JCO.2023.41.16_suppl.6029