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

• DOI: 10.1136/jitc-2021-sitc2021.423
• Publication Date: 2021-11-09T15:15:02Z
• Authors: Russell Pachynski; Melissa Reimers; Cody Weimholt; Katie Slane; Peter Oppelt; Jason Frankel; Robert Figenshau; Eric Kim; Gerald Andriole; Lawrence Fong
• Keywords: Neoadjuvant Therapy

<h3>Background</h3> Treatment of localized prostate cancer with surgery or radiotherapy remains suboptimal failure rates 35–40%.¹ Neoadjuvant androgen deprivation therapy improved pathologic outcomes, but did not significantly impact progression-free overall survival.² Prostate higher density B cells correlates stage disease and risk recurrence progression.³ Elevated levels BTK (Bruton's tyrosine kinase) – an enzyme known to have critical roles in cell function - also been noted compared normal tissue, correlate grade, may play a role tumorigenesis. Preclinical modeling shows pharmacologic suppression inhibits growth cancer.⁴ Ibrutinib, potent inhibitor, can target B-cell signaling pathways has established safety profile. Ibrutinib act reduce immunosuppression by intratumoral cells, which secrete anti-inflammatory IL-10 inhibit Th1 cytotoxic CD8 T activity.⁵ Therefore, we hypothesized that ibrutinib will augment anti-tumor immune responses cancer. <h3>Methods</h3> Accrual began July 2016 for this ongoing trial (NCT02643667). 23 24 planned patients enrolled date. Eligible received no prior treatment their histologically confirmed prostatic adenocarcinoma evidence metastatic disease. Patients must decided upon deemed suitable candidates undergo radical prostatectomy. Following completion initial three patient cohort 840 mg, qd dosing 14 days, all remaining receive mg/day oral 28 days. Radical prostatectomy occur 7–12 days after the last dose ibrutinib. are assessed 4 weeks surgery. The primary objectives assess characterize infiltration within tissue treated reference population. Correlative samples be obtained untreated blood used investigate circulating induced PD-L1 expression tumor immune-infiltrating examined. This is first clinical cancer, lays foundation larger future studies. <h3>Trial Registration</h3> NCT02643667 <h3>References</h3> Kuban DA, Thames HD, Levy LB, et al. Long-term multi-institutional analysis T1-T2 PSA era. <i>Int J Radiat Oncol Biol Phys</i> 2003 Nov 15;<b>57</b>(4):915–28. PubMed PMID: 14575822. Scolieri MJ, Altman A, Resnick MI. hormonal ablative before prostatectomy: review. Is it indicated? <i>J Urol</i> 2000 Nov;<b>164</b>(5):1465–72. 11025684. Woo JR, Liss MA, Muldong MT, Tumor infiltrating B-cells increased tissue. Transl Med</i> 2014 Jan 30;12–30. Pubmed 24475900. Guo W, Liu R, Bhardwaj G, Targeting Btk/Etk novel dual inhibitor. <i>Cell Death Dis</i> Sep 4;<b>5</b>:e1409. 25188519. Gunderson AJ, Coussens LM. mediators as targets solid tumors. <i>Exp Cell Res</i> 2013 Jul 1;<b>319</b>(11):1644–9. 23499742. <h3>Ethics Approval</h3> study ethics approval from Washington University School Medicine IRB (#201808057), participating individuals gave informed consent taking part.