A phase 2 study of ibrutinib as neoadjuvant therapy in patients with localized prostate cancer.

• DOI: 10.1200/jco.2023.41.6_suppl.387
• Publication Date: 2023-03-14T15:22:32Z
• Authors: Cayce Ben Nawaf; Bo Peng; Melissa Andrea Re...; Cody Weimholt; Kathryn Slane; Peter John Oppelt; Jason Frankel; Robert S. Figenshau; Eric H Kim; Gerald L. Andriole; Lawrence Fong; Russell Kent Pach...
• Keywords: breakpoint cluster region; Biochemical recurrence

387 Background: Treatment of localized prostate cancer (PCa) with surgery or radiotherapy remains suboptimal failure rates 35-40%. Bruton’s Tyrosine Kinase (BTK) is seen elevated in PCa tissues compared to normal tissue. Malignant B-cell density has been correlated higher risk aggressive and mitigating that through the BTK proposed mouse models. Ibrutinib a potent inhibitor which targets signaling pathways, an established safety profile, shown inhibit vivo tumor growth pre-clinically. Therefore, we hypothesized ibrutinib will augment anti-tumor immune responses inhibiting tumor-intrinsic via blocking while also inducing favorable T-cell profiles PCa. Methods: We performed neoadjuvant clinical trial (NCT02643667) studying Eligible patients had no prior treatment, deemed suitable for undergoing radical prostatectomy. Patients received 840mg/day oral 28 days followed by prostatectomy 7-12 later. were assessed 4 weeks after surgery. The primary objectives are assess characterize B T cell infiltration. Correlative pre- post- treatment tissue blood samples collected; PD-L1 expression immune-infiltrating cells be examined, BCR TCR clonality diversity evaluated. Results: 22 registered underwent date. early termination 3 due adverse effects 1 discovery surgically unresectable disease. A total 21 prostatectomies. There intra-operative complications attributed ibrutinib. was generally well tolerated 7.1% grade related effects. 2% experienced hepatic dysfunction. most common 1-2 diarrhea (8.2%), fatigue (7.1%), anemia (6.1%). median follow-up time 23.9 months. Median overall survival free have not reached two-year milestone 100%. Sample collection complete correlative analyses ongoing. Safety/tolerability, outcomes, preliminary data reported. Conclusions: This first PCa, lays foundation larger future studies. Clinical information: NCT02643667 .