Nuhad K. Ibrahim, MD, discusses the investigation of eftilagimod alpha plus in hormone receptor–positive HER2-negative or HER2-low metastatic breast cancer in the phase 3 AIPAC-003 trial.
Nuhad K. Ibrahim, professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the investigation of eftilagimod alpha (IMP321) plus in hormone receptor (HR)–positive HER2-negative or HER2-low metastatic breast cancer in the phase 3 AIPAC-003 trial (NCT05747794).
Eftilagimod alpha is a soluble LAG-3 agent known to have a synergistic effect with chemotherapy. Prior data from the randomized phase 2b AIPAC trial (NCT02614833) showed that the addition of eftilagimod alpha to paclitaxel was well tolerated and produced encouraging, sustained pharmacodynamic activity vs placebo plus paclitaxel in patients with HR-positive, HER2-negative disease, Ibrahim begins. This was associated with prolonged overall survival (OS), he adds, noting that these data generated interest in evaluating the combination in a larger population and eftilagimod alpha at a higher dose level.
The randomized, double-blind, placebo-controlled phase 3 trial will include an open-label dose optimization lead-in to determine the optimal biological dose of eftilagimod alpha in this regimen, Ibrahim details. During the lead-in, eftilagimod alpha will be administered at dose levels of 90 mg or 30 mg once every 2 weeks alongside a standard weekly dose of paclitaxel at 80 mg/m2.
Primary end points include the safety and tolerability of each dose level, as well as the optimal biological dose for the phase 3 component. Secondary end points include overall response rate, progression free survival, OS, quality of life, and the pharmacokinetic profile at both doses.
Notably, patients with HR-positive, HER2-negative breast cancer enrolled in the study must have proven resistance to endocrine therapy and be eligible to receive chemotherapy. The trial will also include patients with triple-negative breast cancer who are ineligible for anti–PD-L1 therapy but are eligible to receive frontline paclitaxel. Recruitment for the trial is ongoing.