Clinical-stage biotechnology company Immutep Limited (ASX: IMM) has confirmed the initiation of an integrated Phase II/III trial to evaluate eftilagimod alpha (efti) in combination with paclitaxel for the treatment of metastatic HER2-neg/low breast cancer (MBC).
The trial is known as AIPAC-003 (Active Immunotherapy, Eftilagimod Alpha, and PAClitaxel).
Regulatory approval has been received in the US and Institutional Review Board (IRB) approval has been received in Spain, with approvals in additional countries anticipated to follow shortly. The first patient is expected to be enrolled in early Q2 CY2023.
With its novel mechanism of action to activate antigen-presenting cells, efti has to date safely improved clinical outcomes from anti-PD-(L)1 therapies and standard-of-care chemotherapy,” CEO, Marc Voigt, said.
“We look forward to AIPAC-003 building upon the encouraging synergy seen in our previous Phase IIb trial in metastatic breast cancer, especially with its three key adaptations: same day administration of efti plus paclitaxel, this dual IO-chemotherapy treatment continuing until disease progression, and a new primary endpoint of overall survival.
“The selected Phase II/III trial design allows us to move forward with a risk-balanced approach in MBC, as we continue our prioritized late-stage clinical development with anti-PD- 1 therapy in 1st line head & neck squamous cell carcinoma and 1st line non-small cell lung cancer.”
The Company and the US Food and Drug Administration (FDA) agreed to the integrated Phase II/III trial design for AIPAC-003 that will help inform a Biologics License Application (BLA). Additionally, the trial design incorporates feedback from Scientific Advice meetings with the European Medicines Agency (EMA) to support a Marketing Authorisation Application (MAA).
Based on feedback from the FDA/EMA, the HR+/HER2-neg/low MBC patient population has been expanded to include triple-negative breast cancer (TNBC), an aggressive cancer with limited treatment options, which together account for ~78% of breast cancer cases.
The company and the FDA also agreed to an open-label lead-in component of six to 12 patients to test 90mg efti dosing in combination with paclitaxel driven by efti’s excellent safety profile, along with the FDA’s Project Optimus initiative in oncology.
Additionally, patients will receive same-day administration of efti + paclitaxel that can continue until disease progression, unlike the prior AIPAC trial that administered both on different days and stopped chemotherapy at six months.
The open-label lead-in of up to 12 patients will be followed by a randomized (1:1) portion of the Phase II consisting of up to 58 patients that will receive 30mg efti or 90mg efti to determine the optimal biological dose in combination with paclitaxel.
Depending on the Phase II results, potential regulatory actions and resources, a randomised, double-blinded, placebo-controlled Phase III portion will then follow. The Phase III will have overall survival as the primary objective and may include a specific patient population.
With respect to the late-stage clinical development of efti, the Phase II portion of the MBC trial, the ongoing randomized/controlled Phase II trial in 1st line HNSCC, and the initiation of the registrational trial in 1st line NSCLC are included in the budget and have no impact on the Company’s expected cash runway to the end of the 1st half of calendar year 2024.