Abstract PS1-09-16: Optimal biological dose of eftilagimod alpha, a soluble LAG-3 protein, in metastatic breast cancer patients receiving weekly paclitaxel in AIPAC-003

Background: Eftilagimod alpha (efti) is an MHC class II agonist that mediates activation of antigen presenting cells (APC) like dendritic cells and monocytes, subsequently followed by T cell activation. Aligning with the FDA’s Project Optimus, we designed AIPAC-003 (NCT05747794), a randomized phase 2 trial testing efti plus paclitaxel (P) in metastatic breast cancer (mBC) patients (pts), to test 30 vs 90 mg efti to determine the optimal biological dose (OBD). Methods: Heavily pretreated female pts with HR+ and HER2-negative or HER2-low mBC resistant to endocrine-based therapy (ET) or with metastatic triple-negative breast cancer (mTNBC) not eligible to PD-(L)1-based therapy were enrolled. After an initial safety lead-in that tested a higher 90 mg dose of efti plus P, pts were randomized 1:1 to receive 30 mg or 90 mg efti plus P. Pts received P (80 mg/m2 IV on D1, 8 and 15) followed by efti (30 mg or 90 mg SC on D1 and 15) in a 4-week cycle up to 12 months. Imaging was done Q8W and assessed by the investigator per RECIST 1.1. Predefined dose-limiting toxicities (DLTs) were assessed by an IDMC. The primary objective was to define the OBD of efti. Results: 64 evaluable pts were randomized between May 2023-Sep 2024. 19% of pts had mTNBC. Most were previously treated with ET (89%), including CDK4/6 inhibitors (84%), and considered ET-resistant (81%). Pts had a median age of 58.5 years (range 34-85), and 64% had baseline ECOG 0. Safety data showed that adverse reactions leading to treatment discontinuation occurred in 13% of pts in the 30 mg arm vs 21% in the 90 mg arm (>70% related to paclitaxel toxicity), and two DLTs occurred, both hypersensitivity reactions in the 90 mg arm. A known safety signal of efti, local injection site reactions (LISRs) that were considered long-lasting (≥5 days) occurred in 19.4% of pts in the 30 mg arm and 33.3% of pts in the 90 mg arm. None of these LISRs led to treatment discontinuation. After 8 months minimum of follow-up, time to onset of response was 2.0 months (30 mg) versus 1.9 months (90 mg). Objective response rate (ORR) and disease control rate (DCR) are presented in Table 1. Conclusion: These data show that 90 mg efti is less tolerable and does not enhance efficacy. Therefore, the 30 mg SC dose of the APC activator, efti, previously administered in >500 pts with advanced or metastatic cancer in prior phase 1 and 2 studies, is considered the OBD, suitable for evaluation in larger pt populations. Citation Format: N. K Ibrahim, I. Garcia Fructuoso, F. Forget, P. Chalasani, P. Sánchez Rovira, R. Poncin, J. López, S. Morales Murillo, K. Papadamitriou, S. Winckels, C. Mueller, F. Triebel. Optimal biological dose of eftilagimod alpha, a soluble LAG-3 protein, in metastatic breast cancer patients receiving weekly paclitaxel in AIPAC-003 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-09-16.