Orelabrutinib Wins Approval in China for First-Line CLL and SLL

Chronic Lymphocytic Leukemia |

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China’s National Medical Products Administration (NMPA) has approved the BTK inhibitor orelabrutinib (ICP-022) for the first-line treatment of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).1

Orelabrutinib was investigated in a phase 3 trial (NCT04578613), where patients with previously untreated CLL or SLL were randomly assigned to receive the BTK inhibitor or the combination of chlorambucil and rituximab (Rituxan).2

“Orelabrutinib has demonstrated excellent efficacy and safety in the treatment of B-cell malignancies such as relapsed/refractory CLL/SLL since its launch in 2020, showing a higher complete response [CR] rate,” Jianyong Li, MD, principal investigator of the clinical trial and a professor at the Jiangsu Province Hospital in China, stated in a news release.1 “The first-line approval means more [patients with CLL/SLL] will benefit from this highly effective treatment regimen. The study showed a CR rate as high as 12.1%, which will bring new hope to the treatment of hematological tumors in China.”

Orelabrutinib was previously approved by the NMPA for the treatment of patients with relapsed/refractory CLL/SLL, those with relapsed/refractory mantle cell lymphoma, and patients with relapsed/refractory marginal zone lymphoma.

"Despite the challenges posed by the COVID-19 pandemic in initiating the study, enrolling patients and patient management, orelabrutinib demonstrated significant efficacy and good safety in first-line treatment of CLL/SLL,” Lugui Qiu, MD, principal investigator of the clinical trial and a professor at the Blood Diseases Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, added in a news release. “It also provides an effective treatment option for high-risk patients and those with comorbidities, both in clinical research and real-world settings.”

The phase 3 study included patients at least 18 years of age with previously untreated CLL or SLL who had at least 1 lymph node with a maximum axis of more than 1.5 cm and a measurable vertical dimension.2 Other key inclusion criteria consisted of an ECOG performance status of 0 to 2 and a life expectancy of more than 6 months.

The study excluded patients who had a stroke or intracranial hemorrhage with 6 months of random assignment, and those with hypersensitivity to orelabrutinib, nitrogen mustard benzoate, rituximab, or any other component of the study drugs.

Patients were randomly assigned to receive orelabrutinib at 150 mg once per day, or chlorambucil at 0.5 mg/kg on days 1 and 15 of cycles 1 to 6 plus rituximab at 375 mg/m2 on day 1 of cycle 1, then at 500 mg/m2 on day 1 of cycles 2 to 6.

Progression-free survival (PFS) served as the trial’s primary end point. Secondary end points included objective response rate (ORR), duration of response, and overall survival (OS).

Data for Orelabrutinib in Relapsed/Refractory CLL/SLL

Findings from a single-arm, multicenter, phase 2 trial (NCT03493217) showed that Chinese patients with relapsed/refractory CLL or SLL (n = 80) treated with orelabrutinib at 150 once per day achieved an ORR of 92.5%, comprising a CR rate of 21.3%, a partial response (PR) rate of 60.0%, and a PR with lymphocytosis rate of 11.3%.3

At a median follow-up of 32.3 months, the median PFS was not reached; the 30-month PFS rate was 70.9% (95% CI, 59.5%-79.6%), and the 30-month OS rate was 81.3% (95% CI, 70.8%-88.2%).

Regarding safety, any-grade adverse effects (AEs) occurred in 98.8% of patients; 86.8% of AEs were grade 1 or 2, and 13.2% were grade 3 or higher. The rates of grade 1/2 and grade 3 or higher treatment-related AEs were 64.7% and 9.5%, respectively.

References

1. InnoCare announces approval of orelabrutinib for the first-line treatment of CLL/SLL in China. News release. InnoCare. April 25, 2025. Accessed April 25, 2025. https://www.innocarepharma.com/en/news/activity/en020250425-Approval-of-Orelabrutinib-for-First-line-Treatment-of-CLL-SLL-in-China
2. ICP-022 versus chlorambucil combined with rituximab in the treatment of untreated CLL/​SLL. ClinicalTrials.gov. Updated June 5, 2023. Accessed April 25, 2025. https://clinicaltrials.gov/study/NCT04578613
3. Xu W, Zhou K, Wang T, et al. Orelabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma patients: multi-center, single-arm, open-label, phase 2 study. Am J Hematol. 2023;98(4):571-579. doi:10.1002/ajh.26826