Phase II trial of a novel immunotherapy combination of pembrolizumab and HER2 bi-armed activated T cells (BATs) in metastatic castrate resistant prostate cancer.

97 Background: Immune checkpoint inhibitors (ICI) have demonstrated only modest efficacy in metastatic castrate resistant prostate cancer (mCRPC). Anti-HER2 and Anti-CD3 bispecific antibody armed activated T cells (HER2 BATs) demonstrated efficacy in prostate cancer cell lines, irrespective of HER2 expression status. Safety and preliminary responses in refractory mCRPC were noted in a phase I trial with HER2 BATs. Preclinical synergy was noted in prostate cancer with ICI and BATs. We conducted a phase II study with pembrolizumab and HER2 BATs that would potentially transform immune cells to exhibit cytotoxicity against prostate cancer. Methods: 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. Patients underwent apheresis for mononuclear cell collection which was shipped to the University of Virginia for manufacturing of HER2 BATs, which were infused twice weekly for 4 weeks. Pembrolizumab was administered every 21 days for a maximum duration of 6 months starting 1 week prior to HER2 BATs infusion. Progression was determined by clinical evaluation, PSA, and radiologic assessment at 3 and 6 months and every 6 months thereafter. Results: Twelve patients have been enrolled on the study of which one withdrew consent. Median age was 69 years (Range 57 to 76 years). Five of 11 patients had prior docetaxel chemotherapy. Eight of 11 patients had bone and lymph node metastases, 1 had lymph node metastases only, and 2 had peritoneal metastasis. Median PSA was 111ng/ml [Range 5.2 - 378 ng/ml]. Five and 6 patients had PS of 0 and 1 respectively. The regimen was well tolerated with no unexpected toxicities. To date 3 of 6 patients have completed study treatment and remain progression free at 6 months, 1 death occurred due to an unrelated cause, and 2 patients progressed at 12 weeks of therapy. Two patients demonstrated an 88% and 36% PSA decline. Immune correlates will be presented. Conclusions: The combination regimen of pembrolizumab and BATs appears to be worthy of future exploration in a larger trial in mCRPC. Clinical trial information: NCT03406858.