Tolerability Concerns at Higher Dose Narrow Eftilagimod Alfa’s Path Forward
Immutep Limited reveals promising Phase II results from its AIPAC-003 trial, establishing 30 mg as the optimal biological dose of eftilagimod alfa combined with paclitaxel in metastatic breast cancer patients.
- Phase II AIPAC-003 trial shows strong response rates in heavily pretreated metastatic breast cancer
- 30 mg eftilagimod alfa selected as optimal biological dose following FDA Project Optimus guidelines
- Combination therapy with paclitaxel activates immune biomarkers including lymphocyte count and interferon-gamma
- Higher 90 mg dose linked to increased toxicity and injection site reactions
- Dose selection critical for ongoing Phase III trials in lung cancer and future regulatory filings
Promising Phase II Data in Metastatic Breast Cancer
Immutep Limited has announced encouraging results from its AIPAC-003 Phase II clinical trial, investigating the immunotherapy eftilagimod alfa (efti) in combination with the chemotherapy agent paclitaxel. The study enrolled 66 women with heavily pretreated metastatic breast cancer, including hormone receptor-positive and triple-negative subtypes resistant to standard therapies. Both tested doses of efti, 30 mg and 90 mg, demonstrated strong objective response rates (ORR) and disease control rates (DCR), signaling meaningful clinical activity in this challenging patient population.
The trial’s design aligned with the FDA’s Project Optimus initiative, which emphasizes identifying the optimal biological dose (OBD) rather than relying solely on maximum tolerated dose. This approach aims to balance efficacy with safety and immune activation, a critical consideration for immunotherapies.
Optimal Biological Dose Established at 30 mg
While both dosing levels showed comparable time to response and immune activation, marked by increases in absolute lymphocyte count and interferon-gamma, the 90 mg dose was associated with suboptimal tolerability. Patients experienced dose-limiting toxicities and a higher incidence of local injection site reactions. Consequently, the 30 mg dose was selected as the OBD, meeting FDA criteria and positioning it as the preferred dose for further development.
Dr. Nuhad Ibrahim from MD Anderson Cancer Center highlighted the significance of integrating clinical and pharmacodynamic data to define this dose, reinforcing efti’s novel mechanism of action and its potential in combination therapies.
Strategic Implications for Immutep’s Oncology Pipeline
Defining the OBD at 30 mg carries strategic weight for Immutep’s ongoing and future clinical programs. Notably, the company is advancing a Phase III trial (TACTI-004/KEYNOTE-F91) combining efti with Merck’s KEYTRUDA and chemotherapy in first-line non-small cell lung cancer (NSCLC). The clarity on dosing streamlines regulatory pathways and supports potential future combinations with emerging therapeutic modalities such as antibody-drug conjugates and bispecific antibodies.
CEO Marc Voigt emphasized the commitment to progressing efti’s clinical development globally, underscoring the importance of this milestone in satisfying regulatory expectations and optimizing patient outcomes.
Looking Ahead to SABCS 2025 Presentation
Immutep will present these new data at the upcoming San Antonio Breast Cancer Symposium, offering the oncology community detailed insights into the trial’s findings. This presentation will likely attract attention from clinicians and investors eager to assess efti’s role in the evolving immunotherapy landscape.
While the results are promising, longer-term efficacy and safety data will be essential to fully understand efti’s clinical value. The competitive environment for immunotherapies in breast and lung cancers also presents challenges that Immutep will need to navigate carefully.
Bottom Line?
With the optimal dose now defined, Immutep is poised to accelerate efti’s clinical journey, but upcoming Phase III results will be pivotal for its future.
Questions in the middle?
- How will efti’s 30 mg dose perform in larger Phase III trials across different cancer types?
- What are the long-term safety and durability of response data for efti in metastatic breast cancer?
- How might efti’s immunotherapy-chemo combination compete against existing and emerging treatments?
