![]() Medical writing support was provided by Valerie Hilliard, PhD, and funded by Pharmacyclics LLC, an AbbVie Company. Table: 754Pīest response by prior therapy and organ Response, n (%) No unexpected safety signals were observed. Ibr + pac showed activity in pts with aUC previously treated with platinum-based therapy. Analysis of baseline tumor biopsies (n=43) found that responders (n=18) had a nonsignificant trend toward higher gene expression of ibr targets (BTK, ErbB2, and ITK) vs pts with PD (n=10). Grade ≥3 adverse events occurred in 83% of pts major hemorrhage occurred in 4 pts (6%). One pt (2%) is still on treatment and 7 pts (11%) are still in follow-up. Median duration of response (DOR) was 4 mo (90% CI 3–5) maximum DOR was 24 mo. ![]() ![]() DCR was 65%, with an ORR of 27% and CR of 5% (Table). Median PFS was 4 mo (90% CI 3–4) median OS was 8 mo (90% CI 7–10). 68% of pts previously had a checkpoint inhibitor. Median age was 67 y 54% of pts had 2 prior therapies. ResultsĦ3 pts were treated with ibr (560 mg, n=4 840 mg, n=59) + pac with a median follow-up of 21 mo. Biomarker analysis of baseline tumor biopsies was done by NanoString gene expression assay. Additional endpoints included efficacy (overall response rate, disease control rate, and overall survival ), and safety. The primary endpoint was progression-free survival (PFS). Pts received once-daily ibr (at a starting dose of 560 mg or recommended phase 2 dose of 840 mg) in combination with weekly IV pac 80 mg/m 2 in 21-d cycles until unacceptable toxicity or progressive disease (PD). Pts treated with a prior BTK inhibitor were excluded. ![]() Ibr + pac was assessed in pts with aUC previously treated with platinum-based chemotherapy who had an ECOG performance status of 0–1. The combination of ibr + pac was evaluated in the aUC cohort of the phase 1b/2 study (NCT02599324). In vitro, ibr has been shown to mitigate resistance to pac (Zhang Mol Cancer Ther 2017). Ibr, a once-daily Bruton’s tyrosine kinase (BTK) inhibitor approved for various B-cell malignancies, also inhibits other kinases, such as ITK and ETK (Wang Clin Cancer Res 2018), that are upregulated in UC.
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