What does this research mean for the field?

The optimal biological dose of eftilagimod alpha in metastatic breast cancer patients receiving weekly paclitaxel is 30 mg, as 90 mg is less tolerable and does not enhance efficacy. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The study aims to determine the optimal biological dose of eftilagimod alpha in metastatic breast cancer patients receiving paclitaxel.

February 19, 2026

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

Key Points

The study aims to determine the optimal biological dose of eftilagimod alpha in metastatic breast cancer patients receiving paclitaxel.
Conducted a randomized phase 2 trial (AIPAC-003) in metastatic breast cancer patients.
Patients were randomized to receive 30 mg or 90 mg of eftilagimod alpha along with weekly paclitaxel.
Monitored for adverse reactions and objective response rates over a minimum follow-up of 8 months.
60 patients received either 30 mg or 90 mg of eftilagimod alpha out of 64 evaluable patients.
Treatment discontinuation due to adverse reactions occurred in 13% (30 mg) vs. 21% (90 mg).
90 mg dose showed no enhanced efficacy compared to 30 mg, making the latter the optimal dose.

Abstract

Abstract 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.

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