BTK inhibitor zanubrutinib active in non-Hodgkin lymphomas

ATLANTA – Zanubrutinib (BGB-3111), an investigational BTK inhibitor, was well tolerated and active as a single agent in patients with indolent and aggressive forms of non-Hodgkin lymphoma, according to data presented at the annual meeting of the American Society of Hematology.

Response rates ranged from 31% to 88% depending on the lymphoma subtype. Overall, approximately 10% of patients discontinued the drug because of adverse events, reported Constantine S. Tam, MBBS, MD, of Peter MacCallum Cancer Centre & St. Vincent’s Hospital, Melbourne.

“There was encouraging activity against all the spectrum of indolent and aggressive NHL subtypes … and durable responses were observed across a variety of histologies,” Dr. Tam said.

Zanubrutinib is a second-generation BTK inhibitor that, based on biochemical assays, has higher selectivity against BTK than ibrutinib, Dr. Tam said.

He presented results of an open-label, multicenter, phase 1b study of daily or twice-daily zanubrutinib in patients with B-cell malignancies, most of them relapsed or refractory to prior therapies. The lymphoma subtypes he presented included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL).

For 34 patients with indolent lymphomas (FL and MZL), the most frequent adverse events were petechiae/purpura/contusion and upper respiratory tract infection. Eleven grade 3-5 adverse events were reported, including neutropenia, infection, nausea, urinary tract infection, and abdominal pain.

Atrial fibrillation was observed in two patients in the aggressive NHL cohort, for an overall AF rate of approximately 2%, Dr. Tam said.

For 65 patients with aggressive lymphomas (DLBCL and MCL), the most frequent adverse events were petechiae/purpura/contusion and diarrhea; 27 grade 3-5 adverse events were reported, including neutropenia, pneumonia, and anemia.

The highest overall response rate reported was for MCL, at 88% (28 of 32 patients) followed by MZL at 78% (7 of 9 patients), FL at 41% (7 of 17 patients), and DLBCL 31% (8 of 26 patients).

The recommended phase 2 dose for zanubrutinib is either 320 mg/day once daily or a split dose of 160 mg twice daily, Dr. Tam said.

Based on this experience, investigators started a registration trial of zanubrutinib in combination with obinutuzumab for FL, and additional trials are planned, according to Dr. Tam.

There are also registration trials in Waldenstrom macroglobulinemia and chronic lymphocytic leukemia based on other data suggesting activity of zanubrutinib in those disease types, he added.

Zanubrutinib is a product of BeiGene. Dr. Tam reported disclosures related to Roche, Janssen Cilag, Abbvie, Celgene, Pharmacyclics, Onyx, and Amgen.

SOURCE: Tam C et al, ASH 2017, Abstract 152

ATLANTA – Zanubrutinib (BGB-3111), an investigational BTK inhibitor, was well tolerated and active as a single agent in patients with indolent and aggressive forms of non-Hodgkin lymphoma, according to data presented at the annual meeting of the American Society of Hematology.

Response rates ranged from 31% to 88% depending on the lymphoma subtype. Overall, approximately 10% of patients discontinued the drug because of adverse events, reported Constantine S. Tam, MBBS, MD, of Peter MacCallum Cancer Centre & St. Vincent’s Hospital, Melbourne.

“There was encouraging activity against all the spectrum of indolent and aggressive NHL subtypes … and durable responses were observed across a variety of histologies,” Dr. Tam said.

Zanubrutinib is a second-generation BTK inhibitor that, based on biochemical assays, has higher selectivity against BTK than ibrutinib, Dr. Tam said.

He presented results of an open-label, multicenter, phase 1b study of daily or twice-daily zanubrutinib in patients with B-cell malignancies, most of them relapsed or refractory to prior therapies. The lymphoma subtypes he presented included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL).

For 34 patients with indolent lymphomas (FL and MZL), the most frequent adverse events were petechiae/purpura/contusion and upper respiratory tract infection. Eleven grade 3-5 adverse events were reported, including neutropenia, infection, nausea, urinary tract infection, and abdominal pain.

Atrial fibrillation was observed in two patients in the aggressive NHL cohort, for an overall AF rate of approximately 2%, Dr. Tam said.

For 65 patients with aggressive lymphomas (DLBCL and MCL), the most frequent adverse events were petechiae/purpura/contusion and diarrhea; 27 grade 3-5 adverse events were reported, including neutropenia, pneumonia, and anemia.

The highest overall response rate reported was for MCL, at 88% (28 of 32 patients) followed by MZL at 78% (7 of 9 patients), FL at 41% (7 of 17 patients), and DLBCL 31% (8 of 26 patients).

The recommended phase 2 dose for zanubrutinib is either 320 mg/day once daily or a split dose of 160 mg twice daily, Dr. Tam said.

Based on this experience, investigators started a registration trial of zanubrutinib in combination with obinutuzumab for FL, and additional trials are planned, according to Dr. Tam.

There are also registration trials in Waldenstrom macroglobulinemia and chronic lymphocytic leukemia based on other data suggesting activity of zanubrutinib in those disease types, he added.

Zanubrutinib is a product of BeiGene. Dr. Tam reported disclosures related to Roche, Janssen Cilag, Abbvie, Celgene, Pharmacyclics, Onyx, and Amgen.

SOURCE: Tam C et al, ASH 2017, Abstract 152

ATLANTA – Zanubrutinib (BGB-3111), an investigational BTK inhibitor, was well tolerated and active as a single agent in patients with indolent and aggressive forms of non-Hodgkin lymphoma, according to data presented at the annual meeting of the American Society of Hematology.

Response rates ranged from 31% to 88% depending on the lymphoma subtype. Overall, approximately 10% of patients discontinued the drug because of adverse events, reported Constantine S. Tam, MBBS, MD, of Peter MacCallum Cancer Centre & St. Vincent’s Hospital, Melbourne.

“There was encouraging activity against all the spectrum of indolent and aggressive NHL subtypes … and durable responses were observed across a variety of histologies,” Dr. Tam said.

Zanubrutinib is a second-generation BTK inhibitor that, based on biochemical assays, has higher selectivity against BTK than ibrutinib, Dr. Tam said.

He presented results of an open-label, multicenter, phase 1b study of daily or twice-daily zanubrutinib in patients with B-cell malignancies, most of them relapsed or refractory to prior therapies. The lymphoma subtypes he presented included diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL).

For 34 patients with indolent lymphomas (FL and MZL), the most frequent adverse events were petechiae/purpura/contusion and upper respiratory tract infection. Eleven grade 3-5 adverse events were reported, including neutropenia, infection, nausea, urinary tract infection, and abdominal pain.

Atrial fibrillation was observed in two patients in the aggressive NHL cohort, for an overall AF rate of approximately 2%, Dr. Tam said.

For 65 patients with aggressive lymphomas (DLBCL and MCL), the most frequent adverse events were petechiae/purpura/contusion and diarrhea; 27 grade 3-5 adverse events were reported, including neutropenia, pneumonia, and anemia.

The highest overall response rate reported was for MCL, at 88% (28 of 32 patients) followed by MZL at 78% (7 of 9 patients), FL at 41% (7 of 17 patients), and DLBCL 31% (8 of 26 patients).

The recommended phase 2 dose for zanubrutinib is either 320 mg/day once daily or a split dose of 160 mg twice daily, Dr. Tam said.

Based on this experience, investigators started a registration trial of zanubrutinib in combination with obinutuzumab for FL, and additional trials are planned, according to Dr. Tam.

There are also registration trials in Waldenstrom macroglobulinemia and chronic lymphocytic leukemia based on other data suggesting activity of zanubrutinib in those disease types, he added.

Zanubrutinib is a product of BeiGene. Dr. Tam reported disclosures related to Roche, Janssen Cilag, Abbvie, Celgene, Pharmacyclics, Onyx, and Amgen.

SOURCE: Tam C et al, ASH 2017, Abstract 152