Safety and efficacy of birelentinib, a novel LYN/BTK dual inhibitor, in relapsed/refractory diffuse large B-cell lymphoma: a phase 2 study (TAI-SHAN9)

In this phase 2 TAI-SHAN9 study, we evaluated the safety and efficacy of birelentinib, a first-in-class oral dual inhibitor of LYN and BTK, in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). A total of 58 patients were enrolled and received birelentinib at doses ranging from 25 to 75 mg once daily (QD). Antitumor efficacy was observed at 50 mg and above, among 42 efficacy-evaluable patients treated at 50 mg or 75 mg QD, overall objective response rate (ORR) was 47.6% (20/42) and complete response rate (CRR) was 31.0% (13/42). Responses were observed across GCB (ORR 58.3%) and non-GCB (ORR 44.8%) subtypes, as well as across the MCD-like, TP53 Mut , and NOS molecular subtypes (each ORR 50.0%). At a median follow-up of 9.2 months for complete responders, the median DoR was not reached, with the longest ongoing CR exceeding 9.3 months. The grade ≥3 treatment-related adverse events included thrombocytopenia (20.7%), neutropenia (12.1%), and pneumonia (5.2%). No major bleeding, atrial fibrillation, or drug-related death was reported. These results suggest that birelentinib is a promising oral treatment for r/r DLBCL across molecular subtypes. Further clinical evaluation of LYN/BTK dual inhibition is warranted. Clinical trial information: ClinicalTrials.gov NCT06539195.

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Publication Details

Journal
Blood Cancer Journal
Published
2026-09-08
DOI
https://doi.org/10.1038/s41408-026-01617-5
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
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article

Safety and efficacy of birelentinib, a novel LYN/BTK dual inhibitor, in relapsed/refractory diffuse large B-cell lymphoma: a phase 2 study (TAI-SHAN9)

Zhiming Li, Lugui Qiu, Mimi Zheng, Mei Lan et al.
Blood Cancer Journal
Lymphoma Diagnosis and Treatment
article

Safety and efficacy of birelentinib, a novel LYN/BTK dual inhibitor, in relapsed/refractory diffuse large B-cell lymphoma: a phase 2 study (TAI-SHAN9)

Zhiming Li, Lugui Qiu, Mimi Zheng, Mei Lan, Wei Liu, Wenbin Qian, Yajun Li, L. Qiu, Keshu Zhou, Zengjun Li, Kaiyang Ding, Ming Jiang, Yu Bai, Hongmei Jing, Fang Zhu, Pengcheng He, Ziyi Liu
article en

Abstract

In this phase 2 TAI-SHAN9 study, we evaluated the safety and efficacy of birelentinib, a first-in-class oral dual inhibitor of LYN and BTK, in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). A total of 58 patients were enrolled and received birelentinib at doses ranging from 25 to 75 mg once daily (QD). Antitumor efficacy was observed at 50 mg and above, among 42 efficacy-evaluable patients treated at 50 mg or 75 mg QD, overall objective response rate (ORR) was 47.6% (20/42) and complete response rate (CRR) was 31.0% (13/42). Responses were observed across GCB (ORR 58.3%) and non-GCB (ORR 44.8%) subtypes, as well as across the MCD-like, TP53 Mut , and NOS molecular subtypes (each ORR 50.0%). At a median follow-up of 9.2 months for complete responders, the median DoR was not reached, with the longest ongoing CR exceeding 9.3 months. The grade ≥3 treatment-related adverse events included thrombocytopenia (20.7%), neutropenia (12.1%), and pneumonia (5.2%). No major bleeding, atrial fibrillation, or drug-related death was reported. These results suggest that birelentinib is a promising oral treatment for r/r DLBCL across molecular subtypes. Further clinical evaluation of LYN/BTK dual inhibition is warranted. Clinical trial information: ClinicalTrials.gov NCT06539195.

Blood Cancer Journal
Union Hospital (HK), Central South University (CN), Sun Yat-sen University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Sichuan University (CN), Tianjin Medical University Cancer Institute and Hospital (CN), Zhengzhou University (CN), West China Hospital of Sichuan University (CN), Linyi People's Hospital (CN), Shandong Tumor Hospital (CN), Hunan Cancer Hospital (CN), The People's Hospital of Guangxi Zhuang Autonomous Region (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), Anhui Provincial Hospital (CN), Peking University Third Hospital (CN), Henan Cancer Hospital (CN), Sun Yat-sen University Cancer Center (CN), Institute of Hematology & Blood Diseases Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Shandong First Medical University (CN), First Hospital of Xi'an (CN), Huazhong University of Science and Technology (CN)
Openalex Percentile: Top 11%
Lymphoma Diagnosis and Treatment
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