Orelabrutinib Receives Approval in Singapore for Marginal Zone Lymphoma

The Health Sciences Authority of Singapore has cleared the use of the BTK inhibitor orelabrutinib (Hibruka; formerly ICP-022) in adult patients with relapsed or refractory marginal zone lymphoma (MZL), according to an announcement from InnoCare Pharma.1

Prior data from a multicenter, open-label, phase 2 study (NCT03797456) showed that at a median follow-up of 24.3 months (interquartile range [IQR], 16.2-27.7), the agent elicited an independent review committee (IRC)–assessed objective response rate (ORR) of 58.9% (95% CI, 48.0%-69.2%) in patients with MZL (n = 90), which comprised a complete response rate of 11.1% and a partial response rate of 47.8%.1 Moreover, the median time to response (TTR) was 5.8 months (95% CI, 3.8-14.2) and the median duration of response was 34.3 months (95% CI, not reached [NR]-NR]).

Moreover, the median IRC-assessed progression-free survival (PFS) was NR. The 12- and 24-month PFS rates were 82.8% (95% CI, 72.6%-89.5%) and 75.8% (95% CI, 63.9%-84.2%). The median time to progression (TTP) was NR, with disease progression rates of 13.7% (95% CI, 7.8%-23.6%) and 21.1% (95% CI, 13.1%-33.0%) at 12 and 24 months, respectively. Additionally, the median overall survival (OS) was NR; the OS rate at 12 months was 91.0% (95% CI, 82.8%-95.4%) and 86.8% (95% CI, 77.2%-92.5%) at 24 months.

“We are excited to obtain a second indication approval in Singapore. As a highly selective BTK inhibitor, orelabrutinib has demonstrated good efficacy and safety in the treatment of R/R MZL,” Jasmine Cui, PhD, co-founder, chairwoman, and chief executive officer of InnoCare, stated in a news release.1 “The approval in Singapore will offer a new treatment option to local lymphoma patients. In addition to lymphoma, we are advancing global clinical trials for orelabrutinib in autoimmune diseases.”

What Were the Eligibility Criteria for the Phase 2 Trial Examining Orelabrutinib?

The trial enrolled patients2 who:

• Were at least 18 years of age but no older than 75 years of age
• Had MZL and indications for treatment initiation
• Had received at least 1 but no more than 4 prior therapies, including acceptable treatment with an anti-CD20 monoclonal antibody and experienced relapse or did not respond
• Had an ECOG performance status ranging from 0 to 2
• Had at least 1 measurable lesion outside of the spleen
• Had acceptable organ function

What Was the Study Design and Key Patient Characteristics?

Participants in the trial received orelabrutinib at a once-daily dose of 150 mg n 28-day cycles. Treatment with the BTK inhibitor continued until progressive disease, unacceptable toxicity, withdrawn consent, or death. The primary end point of the study was ORR and secondary end points included investigator-assessed ORR, PFS, DOR, TTR, TTP, and OS. Investigators also evaluated safety outcomes and the pharmacokinetic profile or orelabrutinib.

In the 90 evaluable patients, the median age was 62.0 years (IQR, 54.0-66.0) with just under half (41.1%) aged 65 years or older. Moreover, 54.4% of patients were male; 53.3% had an ECOG performance status of 1 and 46.7% had status of 0. Regarding subtype, 46.7% of patients had mucosa-associated lymphoid tissue, 35.6% had nodal MZL, and 5.6% had splenic MZL; this information was unknown for 12.2% of patients. Most patients had stage IV disease (75.6%), followed by stage II (11.1%), and stages I and III (6.7% each). Moreover, 46.7% of patients had relapsed disease and 35.6% had refractory disease; 17.8% had both relapsed and refractory disease. Most patients did not have hepatomegaly or splenomegaly.

Regarding prior treatment, 54.4% of patients had received 1 prior line of therapy, 34.4% had received 2 prior lines, and 11.1% had received 3 prior lines. Prior therapies included antib-CD20 monoclonal antibody–based therapy (92.2%), surgery (42.2%), radiotherapy (13.3%), and other (3.3%).

What Was Learned About the Safety Profile of Orelabrutinib?

Of the 111 safety-evaluable patients, 98.2% experienced an adverse effect (AE); 90.1% of patients experienced at least 1 AE related to orelabrutinib. The most common all grade treatment-related AEs (TRAEs) experienced by at least 10% of patients included anemia (27.9%), decreased neutrophil count (23.4%), decreased white blood cell count (18.0%), decreased platelet count (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory infection (10.8%).

The most frequently experienced grade 3 or higher TRAEs reported in at least 2% of patients comprised decreased neutrophil count (8.1%), pneumonia (6.3%), anemia (4.5%), decreased white blood cell count (3.6%), subcutaneous hemorrhage (2.7%), increased alanine aminotransferase levels (1.8%), decreased platelet count (1.8%), upper respiratory infection (1.8%), and hypertension (1.8%). Pneumonia was listed as a serious TRAE, and it was observed in 5.4% of patients. A total of 7 patients discontinued the BTK inhibitor because of TRAEs.

More About Orelabrutinib

1. In June 2021, the FDA granted breakthrough therapy designation to orelabrutinib for use as a potential therapeutic option in patients with relapsed or refractory mantle cell lymphoma.3
2. In April 2025, the National Medical Products Administration of China approved orelabrutinib for first-line use in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma.4

References

1. InnoCare announces approval of Hibruka (orelabrutinib) for the treatment of marginal zone lymphoma in Singapore. News release. InnoCare Pharma. September 7, 2025. Accessed September 10, 2025. https://www.globenewswire.com/news-release/2025/09/08/3145779/0/en/InnoCare-Announces-Approval-of-HIBRUKA-Orelabrutinib-for-the-Treatment-of-Marginal-Zone-Lymphoma-in-Singapore.html
2. Deng L, Li Z, Zhang H, et al. Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: A phase 2, multicenter, open-label study. Am J Hematol. 2023;98(11):1742-1750. doi:10.1002/ajh.27064
3. InnoCare announces breakthrough therapy designation of orelabrutinib by US FDA for treatment of R/R MCL. News release. InnoCare Pharma. June 28, 2021. Accessed September 10, 2025. https://www.prnewswire.com/news-releases/innocare-announces-breakthrough-therapy-designation-of-orelabrutinib-by-us-fda-for-treatment-of-rr-mcl-301320811.html
4. InnoCare announces approval of orelabrutinib for the first-line treatment of CLL/SLL in China. News release. InnoCare. April 25, 2025. Accessed September 10, 2025. https://www.innocarepharma.com/en/news/activity/en020250425-Approval-of-Orelabrutinib-for-First-line-Treatment-of-CLL-SLL-in-China