Phase II trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody Armed Activated T Cells in Metastatic Castrate Resistant Prostate Cancer.

A phase II study was conducted to evaluate the safety and efficacy of the combination of HER2 BATs and programmed death -1 (PD-1) inhibitor, pembrolizumab.

Metastatic castrate resistant prostate cancer (mCRPC) patients with 0-1 performance status (PS) and normal liver, kidney and marrow function, pre or post docetaxel chemotherapy were eligible. Primary endpoint was 6 month progression free survival. Peripheral blood mononuclear cells (PBMC) were obtained by a single apheresis, shipped to University of Virginia, activated with OKT3 and expanded for 14 days in IL-2, harvested, and armed with HER2Bi and cryopreserved. HER2 BATs were infused twice weekly for 4 weeks and pembrolizumab was administered every 21 days for a maximum duration of 6 months starting 1-3 weeks prior to HER2 BATs infusion.

Fourteen patients were enrolled with a median age of 69 (range 57-82 years) and median PSA of 143.4 (range 8.2 - 4210 ng/dL). Two patients had peritoneal metastases, 1 had lymph node (LN) only metastases and 11 had bone metastases of which 7 had bone and LN metastases. All were pretreated with androgen receptor axis targeted agents and 7 (50%) had prior docetaxel chemotherapy. The toxicities were grade1-2 infusion reactions with fever, chills, headaches, nausea and/or myalgias. Primary endpoint of 6 month progression free survival (PFS) was achieved in 5 of 14 patients (38.5%, 95%CI 19.5%-76.5%). Median PFS was 5 months and median survival was 31.6 months.

The safety and promising efficacy makes this combination worthy of future investigation in mCRPC.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Oct 18 [Epub ahead of print]

Ulka N Vaishampayan, Archana Thakur, Wei Chen, Abhinav Deol, Meera Patel, Kimberlee Dobson, Brenda Dickow, Dana Schalk, Amy Schienschang, Sarah Whitaker, Amanda Polend, Joseph A Fontana, Elisabeth I Heath, Lawrence G Lum

University of Michigan Medical School, Ann Arbor, Michigan, United States., University of Virginia, Charlottesville, VA, United States., Wayne State University, Detroit, MI, United States., Karmanos Cancer Institute, Detroit, Michigan, United States., Karmanos Cancer center, Detroit, MI, United States., Karmanos Cancer Center, Detroit, United States., Wayne State University/Karmanos Cancer Institute, Detroit, MI, United States., University of Virginia, United States., John D. Dingell VA Medical Center, Wayne State University, Karmanos Cancer Institute, Detroit, MI, United States., Karmanos Cancer Center, Detroit, MI, United States., University of Virginia Health System, Charlottesville, VA, United States.

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