Immutep Limited has announced a research collaboration with The George Washington University Cancer Center to evaluate eftilagimod alfa (efti) in a Phase II neoadjuvant trial for early-stage HR+/HER2-negative breast cancer patients. The investigator-initiated study represents the second trial to assess efti in earlier-stage disease, where its unique immune activation mechanism may drive optimal therapeutic benefit.
Trial Design and Patient Population
The multi-center study will treat up to 50 evaluable patients in a two-stage design, focusing on Stage I-III HR+/HER2-negative breast cancer patients eligible for neoadjuvant chemotherapy. The trial protocol involves treating enrolled patients with efti monotherapy administered subcutaneously for three weeks, followed by standard neoadjuvant chemotherapy in combination with efti prior to surgery.
The study will be primarily funded by grants and The George Washington University Cancer Center, with Immutep providing efti at no cost, technical support, and limited funding within its existing budget. Principal Investigator Dr. Pavani Chalasani, Division Director of Hematology and Medical Oncology at the GW Cancer Center, will lead the trial.
Mechanism of Action and Clinical Rationale
Efti operates as a first-in-class antigen presenting cell (APC) activator, binding to MHC Class II molecules on APCs to stimulate both innate and adaptive immunity. This mechanism leads to activation and proliferation of cytotoxic CD8+ T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. The drug also upregulates expression of key biological molecules including IFN-γ and CXCL10, further enhancing the immune system's anti-cancer capabilities.
"Given my clinical experience with efti in the AIPAC-003 study coupled with promising data from additional trials evaluating efti in metastatic breast cancer settings, we look forward to evaluating this unique immunotherapy at earlier stage disease," stated Dr. Chalasani. She noted that efti's immune activation in early-stage cancer patients with stronger immune systems may lead to improved disease-free survival.
Primary Endpoint and Clinical Significance
The trial's primary objective is determining pathological complete response (pCR) following neoadjuvant efti treatment and chemotherapy. Dr. Chalasani expressed optimism that efti's "powerful and safe activation of a broad anti-cancer immune response in combination with chemotherapy may lead to high rates of pathologic complete responses."
The immunotherapy has demonstrated encouraging clinical results in metastatic disease and showed promise in its initial neoadjuvant trial for soft tissue sarcoma. Efti's mechanism allows CD8+ T cells to be armed in vivo with chemotherapy-induced tumor antigens, potentially enhancing therapeutic efficacy.
Strategic Development and Regulatory Status
Immutep CEO Marc Voigt emphasized the collaboration's strategic value, stating the trial "helps us cost-efficiently expand our clinical pipeline for neoadjuvant efti in areas of high unmet need." He expressed confidence that this "novel immune system activator can play a meaningful role in metastatic settings and in the ongoing expansion of immunotherapy into neoadjuvant settings."
Efti is currently under evaluation across multiple solid tumor types, including non-small cell lung cancer, head and neck squamous cell carcinoma, and metastatic breast cancer. The drug's favorable safety profile enables various combination approaches with anti-PD-(L)1 immunotherapy and chemotherapy. The FDA has granted efti Fast Track designation for first-line treatment in both head and neck squamous cell carcinoma and non-small cell lung cancer.
The trial is registered on clinicaltrials.gov under identifier NCT07102940, marking another step in expanding immunotherapy applications to earlier-stage cancer treatment settings.
