SAFETY AND ACTIVITY OF THE HIGHLY SPECIFIC BTK INHIBITOR, BGB‐3111 PLUS OBINUTUZUMAB IN PATIENTS (PTS) WITH FOLLICULAR LYMPHOMA (FL) AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Abstract

Introduction: BGB‐3111 is a potent and irreversible Bruton tyrosine kinase (BTK) inhibitor, designed to minimize off target inhibition of other TEC‐ and EGFR‐family kinases. BGB‐3111 has significantly less inhibitory effect against ITK and does not inhibit ITK‐mediated rituximab (R)‐induced antibody‐dependent cell‐mediated cytotoxicity (ADCC). BGB‐3111 has shown significant activity in a variety of B‐cell malignancies, especially CLL/small lymphocytic leukemia (SLL) and Waldenström macroglobulinemia (Blood 2016;128:642; Blood 2016;128:1216). Obinutuzumab (O) is a second‐generation anti‐CD20 humanized monoclonal antibody that has increased ADCC activity vs R and is more effective than R when combined with chemotherapy in CLL/SLL and FL. Preliminary results of a phase 1b study of BGB‐3111 plus O in pts with CLL/SLL and FL are presented. Methods: This is an ongoing, open‐label, multicenter, phase 1b study of the combination of BGB‐3111 and O in pts with B‐cell malignancies with indication‐specific expansion cohorts. Reported here are interim safety and activity results for the CLL/SLL and FL cohorts. Results: As of 15 Dec 2016, 40 pts with CLL/SLL (17 pts with treatment‐naïve [TN]; 23 pts with relapsed/refractory [R/R]), and 13 pts with FL were enrolled. Demographic and disease characteristics are shown in Table 1. Median follow‐up time was 4.1 months for CLL/ SLL and 6.2 months for FL. BGB‐3111 plus O was well tolerated. No fatal adverse events (AEs) occurred; only 1 AE led to treatment discontinuation (squamous cell carcinoma in a pt with prior squamous cell carcinoma). Serious AEs (SAEs) were reported in 25.0% of CLL/SLL pts and 23.1% of FL pts; there was only 1 SAE related to O (infusion‐related reaction) and 1 SAE related to BGB‐3111 (pneumonia). There were no AEs of atrial fibrillation. Pts were evaluable for response if they had completed baseline and ≥1 on‐treatment response assessment. Objective response rates (complete response [CR] + partial response + partial response with lymphocytosis) were 88.9%, 86.7%, and 81.8% inTN CLL/SLL, R/R CLL/SLL, and R/R FL, respectively, with 3 CRs in R/R CLL/SLL and 5 CRs in FL. Two pts (1 R/R CLL;1 FL) experienced disease progression; no instances of disease transformation occurred. Conclusions: BGB‐3111 plus O is well tolerated and highly active in CLL/SLL and FL. Most notably, the response rate in FL appears to be higher than that reported with BTK inhibitors or anti‐CD20 therapy alone. (Table Presented).