China's NMPA Approves Pirtobrutinib Across CLL

China's National Medical Products Administration (NMPA) has approved pirtobrutinib (Jaypirca) for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), expanding the agent's indication in China to all lines of therapy regardless of prior covalent BTK inhibitor treatment.¹

The approval is supported by data from the phase 3 BRUIN CLL-313 (NCT05023980) and BRUIN CLL-314 (NCT05254743) trials.

In a pooled analysis of treatment-naive patients who received pirtobrutinib across both trials (n = 253), presented at the 2026 EHA Congress, the overall response rate (ORR) was 93.3% (95% CI, 89.5%-96.0%).² ORRs in the pirtobrutinib monotherapy arms of BRUIN CLL-313 (n = 141) and BRUIN CLL-314 (n = 112) were 94.3% (95% CI, 89.13%-97.52%) and 92.0% (95% CI, 85.29%-96.26%), respectively.

Additionally, at a median follow-up of 27.7 months (range, 27.6-27.7), the 24-month progression-free survival (PFS) rate was 93.2% (95% CI, 89.1%-95.8%), and median PFS was not reached (NR; 95% CI, 35.19-not estimable), in the overall population of the pooled analysis. At a median follow-up of 29.5 months (range, 28.9-30.7), the 24-month overall survival (OS) rate was 97.5% (95% CI, 94.6%-98.9%), and median OS was NR.

"As a non-covalent BTK inhibitor, pirtobrutinib offers an important treatment option across the full spectrum of CLL/SLL therapy,” said Hui Zhou, MD, PhD, chief officer of Research and Development in the Oncology Pipeline of Innovent Biologics, in a news release. “The approval across lines of therapy further validates the clinical value of pirtobrutinib in CLL/SLL.

Moreover, the European Medicines Agency's Committee for Medicinal Products for Human Use recommended EU approval of pirtobrutinib across all lines of CLL therapy in June 2026, also based on data from both trials.³

How was BRUIN CLL-313 and BRUIN CLL-314 designed?

BRUIN CLL-313 was a global, randomized, open-label study that compared pirtobrutinib with the chemoimmunotherapy regimen bendamustine plus rituximab (Rituxan; BR) in patients who were 18 years old with previously untreated CLL/SLL without 17p deletions.⁴ Patients also needed to have an ECOG performance status of 2 or less, were not included if they had known central nervous system involvement or Richter transformation.

Patients were randomly assigned to receive 200 mg of daily oral pirtobrutinib (n = 141) or 90 mg/m² of intravenous bendamustine on days of 1 and 2 plus 375 mg/m² of rituximab on day 1 of the first cycle then 500 mg/m² on day 1 of the next 5 28-day cycles (n = 141).

The primary end point was PFS assessed by an independent review committee (IRC), whereas secondary end points were OS, investigator-assessed PFS, safety, and tolerability.³

In BRUIN-313 specifically, pirtobrutinib reduced the risk of IRC-assessed disease progression or death by 80.1% vs BR (HR, 0.199).¹

BRUIN CLL-314 was a global, multicenter, open-label, trial comparing pirtobrutinib with ibrutinib (Imbruvica) in patients with BTK inhibitor–naive CLL/SLL who were treatment naive or had relapsed/refractory disease.⁵

Eligible patients needed to be at least 18 years of age and have CLL/SLL requiring treatment per 2018 International Workshop on CLL criteria, have an ECOG performance status of 2 or less, and known 17p deletion status by fluorescence in situ hybridization. Enrollment of treatment-naive patients was capped at approximately 30% of the total population.

All patients (n = 662) were randomly assigned to receive continuous pirtobrutinib at 200 mg orally once daily (n = 331) or continuous ibrutinib at 420 mg orally once daily (n = 331).

The primary end point was IRC-assessed ORR. IRC-assessed PFS was a key secondary end point; other secondary end points included investigator-assessed ORR and PFS, ORR, OS, and safety.

What was the safety profile of frontline pirtobrutinib in CLL?

In the pooled analysis, any-grade treatment-emergent adverse effects (TEAEs) occurred in 95.6% of patients, and grade 3 or higher TEAEs occurred in 45.6%.² The most common any-grade TEAEs were COVID-19 (20.6%), upper respiratory tract infection (17.1%), neutropenia (14.3%), anemia (12.7%), diarrhea (11.5%), back pain (10.7%), hypertension (10.7%), and arthralgia (10.3%). Common grade 3 or higher TEAEs included neutropenia (9.9%), anemia (4.8%), and hypertension (4.0%).

Any-grade AEs of special interest occurred in 78.6% of patients, most frequently infection (59.9%), bleeding (32.9%), including hemorrhage (20.2%) and bruising (13.1%). Grade 3 or higher any-grade AEs of special interest occurred in 27.4% of patients and included infection (13.9%), neutropenia (13.5%), anemia (4.8%), and thrombocytopenia (2.0%).

“[No] new safety signals have been observed [with] frontline treatment with pirtobrutinib in either of these studies... [Pirtobrutinib] was an extremely well-tolerated drug,” said Jennifer Woyach, MD, about the analysis in an exclusive interview with OncLive®. Patients are doing very well, and we look forward to being able to provide additional data in the future.”

Woyach is a physician and professor of hematology, director of the Division of Hematology, and coleader of the Leukemia and Hematologic Malignancies Program at The Ohio State University Comprehensive Cancer Center in Columbus.

References

1. Innovent Biologics. Jaypirca (pirtobrutinib) approved in China for a new indication in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) across all lines of therapy. News release. September 28, 2026. Accessed September 28, 2026. https://www.prnewswire.com/news-releases/jaypirca-pirtobrutinib-approved-in-china-for-a-new-indication-in-chronic-lymphocytic-leukemia-cll-small-lymphocytic-lymphoma-sll-across-all-lines-of-therapy-302891339.html
2. Wierda WG, Jurczak W, Garcia Vela JA, et al. Pirtobrutinib in treatment-naïve patients with CLL/SLL: pooled results from BRUIN CLL-313 and BRUIN CLL-314. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PS1701.
3. Eli Lilly and Company. Lilly's Jaypirca (pirtobrutinib) recommended by CHMP for approval in the European Union for adults with chronic lymphocytic leukemia (CLL) across all lines of therapy. News release. June 26, 2026. Accessed September 28, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-jaypirca-pirtobrutinib-recommended-chmp-approval-0
4. Jurczak W, Kwiatek M, Czyz J, et al. BRUIN CLL-313: randomized phase III trial of pirtobrutinib versus bendamustine plus rituximab in untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol. 2026;44(6):466-475. doi:10.1200/JCO-25-02380
5. Woyach JA, Qiu L, Grosicki S, et al. Pirtobrutinib versus ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol. 2026;44(6):476-485. doi:10.1200/JCO-25-02477