Orelabrutinib Earns Australian Approval in Relapsed/Refractory MCL

Orelabrutinib (Hibruka), a Bruton’s tyrosine kinase (BTK) inhibitor, has earned approval from the Therapeutic Goods Administration (TGA) in Australia as a treatment for patients with relapsed/refractory mantle cell lymphoma (MCL), according to a news release from the developer, InnoCare Pharma.¹

The BTK inhibitor was previously assessed in a single-arm phase 1/2 trial (NCT03494179), the most recent findings of which were presented in Blood Advances.² Of note, after a median follow-up of 23.8 months among a population of 106 patients treated with at least 1 dose of orelabrutinib, the objective response rate (ORR) per independent review committee (IRC) assessment was 81.1% (95% CI, 72.4%-88.1%), with 27.4% of patients achieving a complete response (CR). The respective rates per investigator assessment were 82.1% (95% CI, 73.4%-88.9%) and 34.9%.

Moreover, stable disease was observed in 5.7% of patients per both IRC and investigator assessment. The disease control rate (DCR) was 86.8% (95% CI, 78.8%-92.6%) and 87.7% (95% CI, 79.9%-93.3%), respectively.

The median time to response was 1.9 months, with a median duration of response (DOR) of 22.9 months (95% CI, 16.4-not reached [NR]) at the time of data cutoff. A total of 49.6% of patients experienced a DOR of at least 24 months. The median progression-free survival was 22.0 months (95% CI, 13.8-NR), with a 24-month rate of 46.5% in this population.The median overall survival (OS) was NR as of data cutoff, and the 24-month rate was 74.3% (95% CI, 64.4%-81.8%).

Furthermore, among patients who achieved a CR as best overall response (n = 29), the 24-month DOR and PFS rates remained near 80%, and the 24-month OS rate was near 100%.

“The approval of orelabrutinib in Australia marks another important milestone in InnoCare’s global footprint and brings a new treatment option to patients with lymphoma in the region,” Jasmine Cui, PhD, co-founder, chairwoman, and chief executive officer of InnoCare, stated in the news release.¹ “Beyond oncology, we are also advancing global clinical trials of orelabrutinib in autoimmune diseases.”

In the first stage of the study, patients with relapsed/refractory MCL were randomly assigned to receive orelabrutinib at 100 mg twice daily (n = 20) or 150 mg daily (n = 20) of orelabrutinib. After the recommended phase 2 dose was determined to be 150 mg daily, an additional 66 patients were assigned to receive the investigational agent orally in 28-day cycles in the absence of disease progression or unacceptable toxicity.

A total of 79.2% of patients were male, with a median age of 62 years (range, 37-73); 28.3% were 65 years or older. Patients mostly had stage IV disease (73.6%), a Ki-67–positive cell percentage of 30% or more (59.4%), HBcAb-positive disease (52.4%), and an ECOG performance score of 1 (50.0%). Patients received a median of 2 prior lines of therapy, the most common of which included anti-CD20–based therapy (88.7%) and cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (CHOP; 69.8%).

The primary end point of the study was ORR per IRC assessment. Secondary end points included ORR per investigator assessment, DOR, time to response, DCR, PFS, OS, and safety.

A total of 68.9% of patients received at least 1 year of orelabrutinib for a median duration of exposure of 21.1 months (IQR, 7.4-27.4). A total of 89% of patients experienced grade 1 or 2 adverse effects (AEs). The most common AEs included thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), neutropenia (24.5%), leukopenia (19.8%), and anemia (19.8%). The most common grade 3 or higher AEs included thrombocytopenia (13.2%), neutropenia (8.5%), anemia (7.5%), hypertension (5.7%), and pneumonia (5.7%).

References

1. InnoCare announces approval of orelabrutinib in Australia. News release. InnoCare Pharma. May 27, 2026. Accessed May 27, 2026. https://tinyurl.com/2vyc4v7r
2. Deng L-J, Zhou K-S, Liu L-H, et al. Orelabrutinib for the treatment of relapsed or refractory MCL: a phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023;7(16):4349-4357. doi:10.1182/bloodadvances.2022009168