Eftilagimod Alpha/Paclitaxel Combo Shows Improved OS in Metastatic HR+ Breast Cancer Subsets

Hans Wildiers, MD, PhD

The combination of eftilagimod alpha and paclitaxel produced a modest increase in median overall survival (OS) in patients with endocrine-resistant hormone receptor (HR)–positive/HER2-negative metastatic breast cancer; though, the effects were significant in patients younger than 65 years old, had low monocytes, or had more aggressive disease (luminal B), according to a post hoc analysis of the phase 2b IMP321-P011 trial (NCT02614833) that was presented during the 2021 SITC Annual Meeting.¹

Overall, data showed that the median OS was 20.4 months (95% CI, 14.3-25.1) in patients receiving the combination vs 17.5 months (95% CI, 12.9-21.9) in those who received placebo (HR, 0.88; 95% CI, 0.64-1.19; P < .197). However, in the subsets of younger patients, those with low monocytes (<0.25/nl), or those with luminal B disease, the median OS improved between 4.2 months and 19.6 months.

Specifically, in the patients under the age of 65 receiving eftilagimod alpha, the median OS was 22.3 months (95% CI, 15.3-29.6) compared with 14.8 months (95% CI, 10.9-18.5) for those in the placebo group (HR, 0.66; 95% CI, 0.45-0.97; P = .017).

Patients with low monocytes who received eftilagimod alpha/paclitaxel had a median OS of 32.5 months (95% CI, 18.2-NA) vs 12.9 months (95% CI; 7.5-120.4) for patients with low monocytes in the placebo group (HR, 0.44; 95% CI, 0.22-0.88; P = .008).

Furthermore, the median OS in patients with luminal B who received eftilagimod alpha/paclitaxel was 16.8 months (95% CI, 9.9-24.9) vs 12.6 months (95% CI; 10.2-17.3) for patients in the placebo arm (HR, 0.67; 95% CI, 0.41-1.08; P = .049).

"Additional toxicity by eftilagimod alpha was rare, [which was] mainly local injection site reactions, and the quality of life was higher at 6 months in the eftilagimod alpha arm compared to the placebo arm,” lead study author Hans Wildiers, MD, PhD, head of clinic and professor at UZ Leuven in Leuven, Belgium, said in a poster presentation of the data. “The combination of weekly paclitaxel and eftilagimod alpha requires further investigation in metastatic breast cancer.”

Eftilagimod alpha, a soluble LAG-3 protein, binds to a subset of major histocompatibility complex class 2 molecules and mediates activation of antigen-presenting cells (APCs) and CD8 T cells. The study examined its effects when combined with paclitaxel, a standard-of-care chemotherapy regimen after the failure of endocrine-based therapy.

In the trial, 227 patients were randomized 1:1 to receive eftilagimod alpha (n = 114) or placebo/paclitaxel (n = 113). All patients had HR-positive/HER2-negative metastatic breast cancer, with 49.1% classified as luminal B, 35.5% as luminal A, and 15.4% as other. Patients in the trial were heavily pretreated, with a median of 2 prior systemic anticancer regimens. The majority of patients were endocrine resistant (84%), and nearly half were pretreated with CDK4/6 inhibitors (44.2%). Furthermore, 74.8% of patients underwent palliative therapy. The median age was 60 years (range, 24-87).

Patients in both arms received paclitaxel at 80 mg/m2 on days 1, 8, and 15, followed by eftilagimod alpha at 30 mg or placebo on days 2 and 16 for up to 24 weeks. Next, patients entered a 48-week maintenance phase, where they received eftilagimod alpha or placebo every 4 weeks.

Except for 1 patient in the placebo group, all patients received at least 1 dose of medication and were included in the full analysis. In the eftilagimod alpha–arm, 58 patients (50.8%) completed all 6 cycles of chemoimmunotherapy, and 60 patients (52.6%) started maintenance therapy. In the placebo group, 50 patients (44.6%) completed all 6 cycles of chemoimmunotherapy and 54 patients (48.2%) started maintenance therapy.

Regarding safety, most patients on eftilagimod alpha and placebo had at least 1 treatment-emergent adverse event (TEAE) at 99.1% and 100%, respectively; grade 3 or higher TEAEs occurred in 68.4% and 65.2% of patients, respectively. Fatal TEAEs occurred in 2 patients on eftilagimod alpha compared with 3 on placebo. An additional 6 patients discontinued on eftilagimod alpha due to a TEAE vs 7 patients of those who were on placebo. Three patients on eftilagimod alpha discontinued due to hypersensitivity reactions developed following injections; paclitaxel-induced hypersensitivity induced this in 4 patients.

Injection-related reactions, all of which were between grades 1 and 3, were the most common TEAE related to eftilagimod alpha, which occurred in 65.8% of patients vs 11.6% on placebo.

Reference

1. Wildiers H, Armstrong A, Cuypere E, et al. Final results from AIPAC: a phase IIb trial comparing eftilagimod alpha (soluble LAG-3 protein) in combination with weekly paclitaxel in HR+ HER2- MBC. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington DC. Abstract 948. http://dx.doi.org/10.1136/jitc-2021-SITC2021.948