Eftilagimod Alpha Plus Chemotherapy Lead-In Proves Safe in HR+/HER2-Low Breast Cancer

Treatment with eftilagimod alpha 90 mg plus weekly paclitaxel led to no serious treatment-emergent adverse effects (TEAEs) in the 6 patients with hormone receptor (HR)–positive, HER2-negative/low metastatic breast cancer enrolled in the safety lead-in portion of the phase 2/3 AIPAC-003 trial (NCT05747794).¹

All TEAEs that have been observed in this population to date have been characterized as mild.

Additionally, the overall response rate was 50% (n = 3) including 1 complete response and 2 partial responses. The remaining 3 patients experienced stable disease, resulting in a disease control rate of 100%. According to the press release all 6 patients had progressed on available endocrine therapy and CDK4/6 inhibitors.

“Acknowledging the early nature of these results, eftilagimod alpha with paclitaxel historically has shown a dose-dependent effect in metastatic breast cancer and has in some cases also led to stable disease patients becoming partial responders after six months. The biologically active 30 mg dose of eftilagimod alpha, previously the highest dose of eftilagimod alpha ever tested, has demonstrated a stronger immune response and greater efficacy than lower dosing levels (1 mg, 6 mg) in multiple clinical trials,” Immutep wrote in the press release.

Eftilagimod alpha is a soluble LAG-3 protein and MHC Class II agonist that stimulates innate and adaptive tumor immunity. As a first-in-class antigen presenting cell (APC) activator, eftilagimod alpha binds to MHC Class II molecules on APCs, leading to the production of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes as well as upregulation of IFN-ƴ and CXCL10.

On April 8, 2021, the FDA granted fast track designation to eftilagimod alpha as first-line therapy for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma.² The following year the FDA granted fast track designation to the combination of eftilagimod alpha and pembrolizumab (Keytruda) as frontline therapy for patients with non–small cell lung cancer.³

The randomized phase 2 portion of the AIPAC-003 trial, which will include up to 58 patients, is ongoing.1 To be eligible for enrollment, patients must have histologically proven HER2-negative metastatic breast cancer. Patients with HR-positive disease must have disease progression on or after at least 1 line of endocrine-based therapy and be eligible to receive chemotherapy for metastatic disease. Patients with HR-negative disease must be candidates for paclitaxel without PD-(L)1 therapy in the frontline metastatic setting. ECOG performance status of 0 or 1 and expected survival for 3 more or more is also required.⁴

The objective of phase 2 is to determine whether the 90-mg dose is safe and more effective than the 30-mg dose. Once the optimal biologic dose of eftilagimod alpha has been identified the phase 3 double-blind portion will begin, wherein approximately 771 patients will be randomly assigned 2:1 to eftilagimod alpha plus paclitaxel or placebo plus paclitaxel.

The primary end points of the phase 3 portion are overall survival and safety; progression-free survival, objective response rate, quality of life, and pharmacokinetics will be evaluated as secondary end points.

To date 23 patients have been enrolled in this cohort. More information regarding the AIPAC-003 trial will be released later this year.¹

References

1. Immutep announces first clinical data from 90mg dosing of Efti. News release. Immutep. March 5, 2024. Accessed March 7, 2024. https://www.immutep.com/detail/immutep-announces-first-clinical-data-from-90mg-dosing-of-efti.html
2. Immutep receives FDA fast track designation for LAG-3 therapeutics eftilagimod alpha for first-line non-small cell lung cancer. News release. Immutep. October 4, 2022. Accessed March 7, 2024. https://www.immutep.com/detail/immutep-receives-fda-fast-track-designation-for-lag-3-therapeutic-eftilagimod-alpha-for-first-line-non-small-cell-lung-cancer.html
3. Immutep achieves fast track designation from US FDA for efti, a soluble LAG-3 protein, in first line recurrent/metastatic head & neck cancer. News release. Immutep. April 8, 2021. Accessed March 7, 2024. https://www.immutep.com/files/content/investor/press-release/2021/Immutep%20Achieves%20Fast%20Track%20designation%20for%20Efti%20from%20US%20FDA%20-%208Apr2021.pdf
4. Study in metastatic breast cancer patients receiving eftilagimod alpha or placebo in combination with paclitaxel chemotherapy (AIPAC-003). ClinicalTrials.gov. Updated January 19, 2024. Accessed March 7, 2024. https://clinicaltrials.gov/study/NCT05747794