FDA Approves Pirtobrutinib in CLL and SLL

News
Article

The FDA has granted accelerated approval to pirtobrutinib for the treatment of patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma.

Lymphomas: © immimagery - stock.adobe.com

Lymphomas: © immimagery - stock.adobe.com

  • Pirtobrutinib (Jaypirca) was approved by the FDA for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have been treated with at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) and a B-cell lymphoma 2 (BCL-2) inhibitor.1,2
  • The approval is supported by findings from the BRUIN trial (NCT03740529).
  • In January 2023, pirtobrutinib was approved for the treatment of patients with relapsed or refractory (R/R) mantle cell lymphoma.

The FDA has approved pirtobrutinib in R/R CLL and SLL based on findings from the phase 1/2 BRUIN trial.1,2

The overall response rate (ORR) was 72% (95% CI, 63%-80%), and the median duration of response (DOR) was 12.2 months (95% CI, 9.3-14.7). All responses were partial responses.1

The approved dose is 200 mg orally once daily until disease progression or unacceptable toxicity.

"This FDA approval—the second for [pirtobrutinib] in 2023—underscores the impactful clinical benefit of continuing to leverage the BTK pathway with [pirtobrutinib] for patients with CLL or SLL as seen in the BRUIN trial," said Jacob Van Naarden, chief executive officer, Loxo@Lilly, said in a press release.2 "These first 2 indications for [pirtobrutinib] represent the beginning of the eventual impact that we hope [pirtobrutinib] can have for patients, and we look forward to seeing the results of the comprehensive phase 3 development program across CLL, SLL, and MCL."

Further findings from the BRUIN trial presented at the International Workshop on Chronic Lymphocytic Leukemia demonstrated at 80% ORR (95% CI, 65.7%-89.8%) in patients with CLL who had progressed on pirtobrutinib, and retreatment with pirtobrutinib showed a clearance of BTK C481 clones and development of non-C481 clones.3

The open-label, international, single-arm, multicohort trial assessed pirtobrutinib in 108 patients with CLL or SLL who had previously received treatment with a BTK or BCL-2 inhibitor. The primary phase 2 end point was ORR. The secondary end points for phase 2 included DOR, progression-free survival, overall survival, safety, pharmacokinetics, symptomatic response, and functional response.4

For safety, common adverse events (AEs, ≥ 20%) included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. The grade 3 or 4 AEs observed in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts. A total of 32% of patients experienced serious infections, and 10% of patients died from infection.1

REFERENCES:
  1. FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic leukemia. News release. U.S. Food & Drug Administrations. December 1, 2023. Accessed December 4, 2023. https://tinyurl.com/44nzmehd
  2. Jaypirca (pirtobrutinib) now approved by the U.S. FDA for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic leuekmia who have received at least 2 lines of therapy, including a BTK and BCL-2 inhibitor. News release. Eli Lilly and Company. December 1, 2023. Accessed December 4, 2023. https://tinyurl.com/5n8zxrt3
  3. Brown JR, Desikan SP, Nguyen B, et al. Genomic evolution and resistance to pirtobrutinib in covalent BTK-Inhibitor pre-treated chronic lymphocytic leukemia patients: results from the phase I/II BRUIN study. Presented at: 2023 International Workshop on Chronic Lymphocytic Leukemia; October 6-9, 2023; Virtual and Boston, Massachusetts. Abstract 1548587.
  4. A study of oral LOXO-305 in patients with previously treated CLL/SLL or NHL ClinicalTrials.gov. Updated March 8, 2023. Accessed December 4, 2023. https://clinicaltrials.gov/study/NCT03740529
Related Videos
Related Content