P1160: RESULTS OF A PHASE 2 EXPANDED ACCESS STUDY OF ZANUBRUTINIB IN PATIENTS WITH WALDENSTRÖM MACROGLOBULINEMIA

Abstract

Background: Bruton tyrosine kinase (BTK) inhibition is an emerging standard of care for Waldenström macroglobulinemia (WM). Zanubrutinib (ZANU; BGB-3111) is a next-generation BTK inhibitor designed to maximize BTK occupancy and minimize off-target inhibition of TEC- and EGFR-family kinases. ZANU was recently approved by the United States (US) Food and Drug Administration, Health Canada, and the European Union at a dose of 320 mg once daily (QD) or 160 mg twice daily (BID) for the treatment of adult patients (pts) with WM. BGB-3111-216 (NCT04052854) is a single-arm, expanded access study of ZANU for treatment-naïve (TN) pts who are unsuitable for standard chemoimmunotherapy or pts with relapsed refractory (R/R) WM. Aims: To provide real-world experience with ZANU in pts with WM. Methods: Eligible pts with TN or R/R WM were assigned to receive ZANU at a dose of 320 mg QD or 160 mg BID. The primary endpoint was the number of pts enrolled/treated and the number of enrolling sites. Secondary endpoints of safety and efficacy included treatment emergent adverse events (TEAEs) of special interest, disease response (overall response rate [ORR] and very good partial response or better [VGPR+]), progression-free survival (PFS), and overall survival (OS). Response was evaluated by investigator-assessment according to the 6th International Workshop on WM (Br J Haematol. 2013;160(2):171-6) every 6 months at minimum. The study was closed by the sponsor in July 2021 and active pts were transitioned to commercial ZANU via a patient assistance program. Results: Fifty pts with WM (17 TN; 33 R/R), were enrolled from December 2019 to June 2021 across 10 academic and community medical centers in the US. At study entry, median age was 72 years, 54% had intermediate-risk disease, 40% had high-risk disease, and median number of prior therapies for R/R pts was 2. Median treatment exposure was 9.2 months (range 1.4 to 20.0). Thirty-eight (76%) pts had ≥1 TEAE, and 36 (72%) experienced ≥1 TEAE of special interest (Table). Grade ≥3 TEAEs of special interest included hypertension (8%), infection (8%), atrial fibrillation or flutter (2%), neutropenia (2%), and second primary malignancy (2%). No new safety signals were observed. In the 41 pts with ≥1 response evaluation, 39.0% achieved a best overall response (BOR) of VGPR (16; 95% CI, 24.2-55.5). ORR was 85.4% (35; 95% CI, 70.8-94.4), and major response rate was 73.2% (30; 95% CI, 57.1-85.8). Of the 4 pts who achieved a BOR of progressive disease, 3 had IgM values that met partial response criteria before the first 6 months response assessment. PFS and OS were immature due to short follow-up, and the median was not met. Image:Summary/Conclusion: The results of this real-world expanded access study were consistent with the established ZANU profile in WM and other B-cell malignancies when administered as monotherapy at a daily dose of 320 mg orally (either as 160 mg BID or 320 mg QD) in pts with intermediate or high-risk R/R or TN WM.