Trial Testing Eftilagimod Alpha-Chemo Combo for HR-positive Advanced Breast Cancers Now Fully Enrolled

Immunotep has completed patient enrollment for its Phase 2b trial evaluating eftilagimod alpha (IMP321) — an investigational therapy that stimulates the immune system to fight cancer — in combination with standard chemotherapy for women with hormone receptor (HR)-positive and HER2-negative advanced breast cancer.

Combining active immunotherapy with standard cytotoxic chemotherapy regimens, like paclitaxel, is a promising new strategy for people with advanced breast cancers, scientists say.

Chemotherapy induces the death of tumor cells that, when dying, release tumor antigens — proteins that can induce an immune response. These are captured by antigen-presenting cells, or APCs, that have the ability to “present” tumor proteins to other cells of the immune system, namely the cancer fighting T-cells.

“By combining efti with chemotherapy, we hope to boost the body’s immune response against tumour cells and improve treatment outcomes compared to giving chemotherapy alone,” Hans Wildiers, the trial’s lead researcher, said in a press release.

The majority of immunotherapies currently in clinical trials target checkpoint inhibitors, like the PD-1/PD-L1 proteins. These inhibitors play a major role in the suppression of the immune system, allowing tumors to evade immune detection. This strategy has shown good responses in certain breast cancers. However, it has demonstrated limited efficacy in women with advanced HR-positive breast cancer.

“Most studies in metastatic breast cancer, including immune therapy, are focusing on blocking the PD-1/PD-L1 checkpoint pathway, but results have been disappointing in this type of hormone sensitive metastatic breast cancer,” Wildiers said.

“With efti, we hope to activate the immune system more efficiently in hormone sensitive metastatic breast cancer, the most frequent breast cancer subtype,” he added.

Eftilagimod alpha stimulates the activity of APCs, and has been proven to induce sustained immune responses in cancer therapies. The therapy is expected to boost responses to chemotherapy.

The AIPAC study (NCT02614833), ongoing in more than 30 clinical sites across Europe, included 226 patients. It is studying a combination of eftilagimod alpha and standard paclitaxel chemotherapy.

The study is being conducted in two parts. First, participants will receive one of two efti doses in combination with chemotherapy to confirm the optimal dose of treatment. Then, patients will be randomly assigned efti plus paclitaxel or a placebo plus paclitaxel. The goal is to determine if the combination extends the time to disease worsening or death.

Additional efficacy endpoints include the proportion of patients with a partial or complete response to therapy, and overall survival. The first results of the trial are expected by April 2020.

“The completion of recruitment for our Phase IIb AIPAC study is an important milestone for Immutep as this is our largest and most advanced clinical trial. As the first PFS [progression-free survival] data read-out is event-driven, the timeline for reporting remains on track for early in 2020. We sincerely thank our principal investigators, the patients and their families for being part of this study,” said Marc Voigt, Immutep’s CEO.

“APC activators are a new class of drug products that could nicely complement the action of standard of care, either chemotherapy or immune checkpoint inhibitors,” said Frederic Triebel, Immutep’s chief strategy officer and chief medical officer.

“We hope that the results of the AIPAC trial will unequivocally demonstrate the value of APC activators in combined advanced cancer therapies,” Triebel added.