ZANUBRUTINIB (BGB-3111) IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH RELAPSED/REFRACTORY NON-HODGKIN LYMPHOMA
Author(s): ,
Qingyuan Zhang
Affiliations:
Cancer Hospital of Harbin Medical University,Harbin,China
,
Rong Tao
Affiliations:
Xinhua Hospital, Shanghai Jiaotong University School of Medicine,Shanghai,China
,
Zhenyu Li
Affiliations:
The Affiliated Hospital of Xuzhou Medical University,Xuzhou,China
,
Haiyi Guo
Affiliations:
BeiGene (Beijing) Co., Ltd,Beijing,China;BeiGene USA, Inc,San Mateo,United States
,
Meng Ji
Affiliations:
BeiGene (Beijing) Co., Ltd,Beijing,China;BeiGene USA, Inc,San Mateo,United States
,
Lu Zhang
Affiliations:
BeiGene (Beijing) Co., Ltd,Beijing,China;BeiGene USA, Inc,San Mateo,United States
,
Jane Huang
Affiliations:
BeiGene (Beijing) Co., Ltd,Beijing,China;BeiGene USA, Inc,San Mateo,United States
,
Jinhua Zhong
Affiliations:
BeiGene (Beijing) Co., Ltd,Beijing,China;BeiGene USA, Inc,San Mateo,United States
Jianfeng Zhou
Affiliations:
Tongji Hospital, Tongji Medical College,Wuhan,China
EHA Library. Zhou J. 06/12/20; 293760; EP1271
Jianfeng Zhou
Jianfeng Zhou
Contributions
Abstract

Abstract: EP1271

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Bruton tyrosine kinase inhibitors (BTKi) have therapeutic activity in mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia and antitumor activity in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Rituximab is an anti-CD20 monoclonal antibody widely approved for CD20+ non-Hodgkin lymphomas (NHL). Zanubrutinib, a potent and selective BTKi, has good combined activity with rituximab in preclinical studies, with reduced interference of anti-CD20–induced antibody-dependent cellular cytotoxicity.

Aims
This study is evaluating the efficacy, safety, and tolerability of zanubrutinib with rituximab in patients with relapsed/refractory (R/R) NHL.


 

Methods
In this ongoing, single-arm, multicenter phase 2 study (NCT03520920), patients received continuous zanubrutinib 160 mg twice a day orally with 375 mg/m2 IV rituximab on days 1, 8, 15, and 22 of cycle 1 and on day 1 of cycles 4, 6, 8, and 10 until disease progression or unacceptable toxicity. Patients with R/R non-germinal center B-cell–like (non-GCB) DLBCL had prior standard anthracycline ± rituximab-based treatment; patients with FL or marginal zone lymphoma (MZL) had ≥1 prior therapy. All patients had ≥1 measurable lesion at baseline imaging assessment. The primary endpoint is investigator-assessed overall response rate (ORR) using the Lugano classification (Cheson, 2014). Secondary endpoints include duration of response (DOR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), safety, and tolerability.

Results
Four sites in China enrolled and treated 41 patients, including 20 non-GCB DLBCL, 16 FL, and 5 MZL. The median study follow-up was 10.28 months (range, 0.8-19.8 months) at the data cutoff date (Aug. 31, 2019). In total, 27 patients (65.9%) discontinued treatment (18 for progressive disease [PD]; 7 for adverse events; 2 for patient withdrawal). The ORR was 35%, 56.3%, and 60% in the non-GCB DLBCL, FL, and MZL cohorts, respectively. One (5%) non-GCB DLBCL patient, 3 (18.8%) FL patients, and 1 (20%) MZL patient achieved CR. In the non-GCB cohort, the median DOR was 8.79 months (95% CI: 0.72, 14.78), and the median PFS was 3.38 months. The median DOR and median PFS were not reached in the FL and MZL cohorts. The estimated 12-month PFS event-free rates were 17.4%, 66%, and 75% for the non-GCB DLBCL, FL, and MZL cohorts, respectively.

The most frequently reported treatment-emergent adverse events (TEAEs) were neutrophil count decrease (24.4%), white blood cell count decrease (22%), and upper abdominal pain, alanine aminotransferase increase, anemia, pyrexia, and upper respiratory tract infection (6 [14.6%] patients each). Grade ≥3 TEAEs in ≥2 patients were neutrophil count decrease (14.6%), white blood cell count decrease (9.8%), and anemia, dyspnea, hypokalemia, lung infection, and platelet count decrease (2 [4.9%] patients each). Infection and hemorrhage occurred in 34.1% and 26.8% of patients, respectively. Grade ≥3 infection was reported in 9.8% of patients, and no grade ≥3 bleeding events were reported. Three fatal TEAEs were reported in the non-GCB DLBCL cohort (dyspnea, death in setting of PD, and suicide) but none in the FL or MZL cohorts. TEAEs led to treatment discontinuation in 5 DLBCL and 2 FL patients.

Conclusion
This study provided preliminary results for activity of zanubrutinib in combination with rituximab in patients with R/R non-GCB DLBCL, FL, and MZL. Further investigation of zanubrutinib combined with anti-CD20 antibodies in B-cell lymphoma is ongoing.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Follicular lymphoma, Kinase inhibitor, Non-Hodgkin's lymphoma

Abstract: EP1271

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Bruton tyrosine kinase inhibitors (BTKi) have therapeutic activity in mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia and antitumor activity in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Rituximab is an anti-CD20 monoclonal antibody widely approved for CD20+ non-Hodgkin lymphomas (NHL). Zanubrutinib, a potent and selective BTKi, has good combined activity with rituximab in preclinical studies, with reduced interference of anti-CD20–induced antibody-dependent cellular cytotoxicity.

Aims
This study is evaluating the efficacy, safety, and tolerability of zanubrutinib with rituximab in patients with relapsed/refractory (R/R) NHL.


 

Methods
In this ongoing, single-arm, multicenter phase 2 study (NCT03520920), patients received continuous zanubrutinib 160 mg twice a day orally with 375 mg/m2 IV rituximab on days 1, 8, 15, and 22 of cycle 1 and on day 1 of cycles 4, 6, 8, and 10 until disease progression or unacceptable toxicity. Patients with R/R non-germinal center B-cell–like (non-GCB) DLBCL had prior standard anthracycline ± rituximab-based treatment; patients with FL or marginal zone lymphoma (MZL) had ≥1 prior therapy. All patients had ≥1 measurable lesion at baseline imaging assessment. The primary endpoint is investigator-assessed overall response rate (ORR) using the Lugano classification (Cheson, 2014). Secondary endpoints include duration of response (DOR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), safety, and tolerability.

Results
Four sites in China enrolled and treated 41 patients, including 20 non-GCB DLBCL, 16 FL, and 5 MZL. The median study follow-up was 10.28 months (range, 0.8-19.8 months) at the data cutoff date (Aug. 31, 2019). In total, 27 patients (65.9%) discontinued treatment (18 for progressive disease [PD]; 7 for adverse events; 2 for patient withdrawal). The ORR was 35%, 56.3%, and 60% in the non-GCB DLBCL, FL, and MZL cohorts, respectively. One (5%) non-GCB DLBCL patient, 3 (18.8%) FL patients, and 1 (20%) MZL patient achieved CR. In the non-GCB cohort, the median DOR was 8.79 months (95% CI: 0.72, 14.78), and the median PFS was 3.38 months. The median DOR and median PFS were not reached in the FL and MZL cohorts. The estimated 12-month PFS event-free rates were 17.4%, 66%, and 75% for the non-GCB DLBCL, FL, and MZL cohorts, respectively.

The most frequently reported treatment-emergent adverse events (TEAEs) were neutrophil count decrease (24.4%), white blood cell count decrease (22%), and upper abdominal pain, alanine aminotransferase increase, anemia, pyrexia, and upper respiratory tract infection (6 [14.6%] patients each). Grade ≥3 TEAEs in ≥2 patients were neutrophil count decrease (14.6%), white blood cell count decrease (9.8%), and anemia, dyspnea, hypokalemia, lung infection, and platelet count decrease (2 [4.9%] patients each). Infection and hemorrhage occurred in 34.1% and 26.8% of patients, respectively. Grade ≥3 infection was reported in 9.8% of patients, and no grade ≥3 bleeding events were reported. Three fatal TEAEs were reported in the non-GCB DLBCL cohort (dyspnea, death in setting of PD, and suicide) but none in the FL or MZL cohorts. TEAEs led to treatment discontinuation in 5 DLBCL and 2 FL patients.

Conclusion
This study provided preliminary results for activity of zanubrutinib in combination with rituximab in patients with R/R non-GCB DLBCL, FL, and MZL. Further investigation of zanubrutinib combined with anti-CD20 antibodies in B-cell lymphoma is ongoing.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Diffuse large B cell lymphoma, Follicular lymphoma, Kinase inhibitor, Non-Hodgkin's lymphoma

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