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ASX/Media Release Immutep Announces Initiation of Phase II/III Trial for Eftilagimod Alpha plus Paclitaxel in Metastatic Breast Cancer Integrated Phase II/III trial design incorporates feedback from the FDA and EMA and w

Key Takeaway: Immutep Limited has announced the initiation of a Phase II/III trial, AIPAC-003, to assess the efficacy of eftilagimod alpha in combination with paclitaxel for treating metastatic HER2-neg/low breast cancer. The trial has received regulatory approval in the US and Spain, with patient enrollment expected to begin in early Q2 2023. The dual treatment aims to build on previous efficacy data and targets a broader breast cancer patient population, including triple-negative cases. This integrated clinical trial design reflects feedback from both the FDA and EMA, indicating a proactive approach to regulatory compliance.

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POSITIVE FACTORS

  • Initiation of Phase II/III trial is a significant development for Metastatic Breast Cancer.
  • Integrated trial design incorporates FDA and EMA feedback, enhancing regulatory support.
  • Eftilagimod alpha shows promising efficacy and safety, with median overall survival improvements in previous trials.

Full Press Release Details

Immutep Announces Initiation of Phase II/III Trial for
Eftilagimod Alpha plus Paclitaxel in Metastatic Breast Cancer
SYDNEY, AUSTRALIA 14 March 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ( Immutep or the
Company ), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announced the initiation of
AIPAC-003 (Active Immunotherapy, Eftilagimod Alpha, and PAClitaxel), 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). 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.
first-in-class soluble LAG-3 protein targeting MHC Class II ligands on antigen-presenting cells (APC), efti is uniquely
positioned to improve clinical outcomes from standard-of-care chemotherapy. Its activation of APCs (e.g., dendritic cells, monocytes) triggers a broad immune response
that includes significant increases in cytotoxic CD8+ T cells armed with chemo-induced tumour antigens to target cancer. This synergy was demonstrated by the AIPAC Phase IIb trial s encouraging efficacy and safety, including a +2.9-month median overall survival (mOS) improvement, statistically significant mOS improvements between 4.2 to 19.6 months across three pre-specified subgroups, a
statistically significant increase in cytotoxic CD8 T cells that correlated with improved OS, a higher 48% ORR (vs 38% for chemo alone), and a superior Quality of Life preservation.
Immutep CEO, Marc Voigt, said: 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. 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 6 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 randomized, 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.
About Eftilagimod Alpha (Efti)
proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen-presenting cell (APC) activator that
stimulates both innate and adaptive immunity for the treatment of cancer. Efti binds to and activates antigen presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic
cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-y and CXCL10 that further boost the immune system s ability to fight cancer.
Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck
squamous cell carcinoma (HNSCC), and HER2 /HR+ metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1
immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).
Immutep is a clinical stage biotechnology
company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its
expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com.
Australian Investors/Media:
Catherine Strong, Citadel-MAGNUS
Basta, VP, Investor Relations and Corporate Communications
+1 (631) 318 4000; chris.basta@immutep.com
This announcement was authorised for release by the Board of Immutep Limited.
Immutep Limited, Level 33, Australia Square, 264 George Street, Sydney NSW 2000, Australia

Frequently Asked Questions

What is the AIPAC-003 trial about?

The AIPAC-003 trial evaluates eftilagimod alpha plus paclitaxel for metastatic HER2-neg/low breast cancer.

What is eftilagimod alpha's mechanism of action?

Eftilagimod alpha activates antigen-presenting cells, improving immune response against cancer.

How does AIPAC-003 improve upon the previous trial?

AIPAC-003 features same-day drug administration and a new overall survival endpoint.

What patient populations are included in AIPAC-003?

The trial includes HR+/HER2-neg/low and triple-negative breast cancer patients.

What is the trial's primary endpoint?

The primary endpoint of the trial is overall survival.

Last updated: Mar 14, 2023