Immutep's Eftilagimod Alfa Shows Strong Response Rates in Metastatic Breast Cancer, Establishes Optimal Dose for Future Trials
Key Insights
Immutep's AIPAC-003 Phase II trial demonstrated strong objective response rates of 41.9% and 48.5% for eftilagimod alfa combined with paclitaxel in heavily pretreated metastatic breast cancer (search) patients.
The study successfully established 30 mg as the optimal biological dose for eftilagimod alfa, completing FDA's Project Optimus requirements for dose optimization.
Both dosing levels showed substantial immune activation with increases in biomarkers including absolute lymphocyte count and interferon-gamma, supporting the drug's mechanism of action.
Immutep Limited has announced promising results from its AIPAC-003 Phase II trial, demonstrating that eftilagimod alfa (efti) in combination with paclitaxel achieved strong response rates in heavily pretreated metastatic breast cancer (search) patients. The study successfully established 30 mg as the optimal biological dose for the investigational immunotherapy, fulfilling FDA's Project Optimus requirements for dose optimization.
Trial Design and Patient Population
The Phase II study randomized 66 female participants with HR+ and HER2-negative/HER2-low metastatic breast cancer (search) resistant to endocrine-based therapy including CDK4/6 (search) inhibitors, or metastatic triple-negative breast cancer (search) not eligible for PD-(L)1-based therapy. Patients were randomized 1:1 to receive either 30 mg or 90 mg eftilagimod alfa in combination with weekly paclitaxel.
The patient population represented a challenging treatment scenario, with participants having received a median of three prior lines of systemic therapy before enrollment in the study.
Efficacy Results Show Strong Response Rates
Both dosing levels demonstrated robust clinical activity in the evaluable population of 64 patients. The 30 mg eftilagimod alfa group achieved an objective response rate of 41.9% and disease control rate of 87.1%, while the 90 mg group showed an objective response rate of 48.5% and disease control rate of 78.8%.
Time to onset of response was comparable between the two arms, at 2.0 months for the 30 mg group versus 1.9 months for the 90 mg group. The efficacy data was based on a cut-off date of September 15, 2025.
Immune Activation Confirms Mechanism of Action
Both dosing levels elicited the desired pharmacodynamic response consistent with eftilagimod alfa's mechanism of action. The study demonstrated substantial increases in immune activation biomarkers, including absolute lymphocyte count and interferon-gamma, supporting the drug's ability to stimulate immune response against cancer cells.
Dr. Nuhad Ibrahim, Professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center, noted: "Evaluating two biologically active doses allowed us to integrate clinical response data with meaningful pharmacodynamic readouts. In keeping with Project Optimus principles, the study generated rigorous comparative data in heavily pretreated metastatic breast cancer (search) patients showing consistent efficacy measures and immune-activation signals across both arms, reinforcing efti's novel mechanism of action and the clinical potential of this immunotherapy-chemo combination."
Safety Profile Supports 30 mg Dose Selection
While both doses showed clinical activity, tolerability at 90 mg was suboptimal, including dose-limiting toxicities and a higher proportion of local injection site reactions. Based on FDA guidance and advice, 30 mg of eftilagimod alfa administered subcutaneously has been defined as the optimal biological dose.
Strategic Implications for Future Development
The successful completion of FDA's Project Optimus requirements carries significant strategic importance for Immutep's oncology pipeline. Marc Voigt, CEO of Immutep, stated: "We are pleased to conclude this important phase of efti's clinical development and are fully committed to advancing this novel immunotherapy to address the needs of cancer patients globally, especially in light of our ongoing Phase III in 1st line NSCLC."
The established optimal biological dose will be applied across Immutep's entire oncology clinical pipeline and inform potential future combinations with new therapeutic agents such as antibody-drug conjugates and bispecifics, as well as support a potential future Biological License Application.
Ongoing Phase III Development
The AIPAC-003 findings directly support the ongoing global TACTI-004 (KEYNOTE-F91) Phase III trial, which is evaluating eftilagimod alfa in combination with Merck (search)'s anti-PD-1 (search) therapy pembrolizumab and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (search), regardless of PD-L1 expression. This trial is currently in the process of opening sites in the United States.
The results from AIPAC-003 will be presented at the 2025 San Antonio Breast Cancer Symposium on December 10th by Dr. Ibrahim, providing the broader oncology community with detailed insights into this novel LAG-3 (search)-based immunotherapy approach.