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Translational insights from a phase 1, first-in-human (FIH) clinical trial of the anti-HER2 Practice patterns for sequential use of antibody-drug conjugate after antibody-drug 1

By: Yara Abdou, MD,

Date. 12/08/2023

At SABCS 2023, Yara Abdou, MD, a medical oncologist from the University of North Carolina Chapel Hill, discusses a phase one clinical trial titled “Translational Insights from a Phase One: First in Human Clinical Trial of the Anti-HER2.”

In this trial, the focus is on CAR macrophages, a therapy for solid tumors expressing HER2, with 57 percent being breast cancer patients. Dr. Abdou explains the process: patients undergo leukophoresis to obtain monocytes, differentiated into macrophages, and transduced with an adenoviral vector to polarize the macrophage into an M1 phenotype. The CAR gene is encoded, and macrophages are transfused back.

Preliminary evidence suggests the therapy remodels the tumor microenvironment, enhancing antigen presentation, immune cell activation, and recruiting active T cells. The safety profile is encouraging, with cytokine release syndrome being the primary side effect, mostly mild, and self-limiting within 48 hours.

With 14 patients treated, the best overall response rate was stable disease, promising further exploration in metastatic breast cancer patients. Dr. Abdou plans a phase two study, aiming to transition once sufficient data is amassed. An exciting facet involves combining the agent with pembrozilumab, with ongoing enrollment in this sub-cohort.

In closing, Dr. Yara Abdou expresses optimism about the research, leaving the audience with the anticipation of more data and advancements in oncology. Gratitude is extended to Dr. Yara Abdou for sharing insights at SABCS 2023.

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