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The phase 3 BRUIN CLL-313 trial is currently recruiting patients with treatment naïve chronic lymphocytic leukemia or small lymphocytic lymphoma to evaluate the efficacy and safety of pirtobrutinib monotherapy vs bendamustine plus rituximab.
The phase 3 BRUIN CLL-313 trial (NCT05023980) is currently recruiting patients with treatment naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) to evaluate the efficacy and safety of pirtobrutinib (LOXO-305) monotherapy vs bendamustine plus rituximab (Rituxan), according to trial schema presented at the 2022 EHA Congress.1,2
The open-label, global phase 3 study will enroll approximately 250 patients with CLL/SLL with retained 17p deletions. Patients will be randomized 1:1 to receive either oral pirtobrutinib or bendamustine plus rituximab, both administered intravenously. Randomization will be stratified by IGHV mutation status (mutated vs unmutated) and Rai stage (low/intermediate vs high). Patients in the control arm will be permitted to cross over to the pirtobrutinib arm if they experience disease progression.1
To be eligible for the trial, patients must have an ECOG performance status of 2 or less, adequate organ function, and kidney function with an estimated creatine clearance of at least 40 mL per minute. Patients must also have a platelet count of at least 75 x 10⁹/L (≥ 50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin of at least 8 g/dL, and an absolute neutrophil count of at least 0.75 x 10⁹/L.1,2
Patients will be excluded from the trial if they have central nervous system involvement by CLL/SLL, a Richter transformation to diffuse large B-cell lymphoma, significant cardiovascular disease, or prolymphocytic leukemia or Hodgkin lymphoma at any time before enrollment. Except for hormonal therapy, concurrent treatment with an investigational agent of anticancer therapy is not permitted.2
Pirtobrutinib is a highly selective, non-covalent BTK inhibitor. The agent inhibits both wild type and C481-mutant BTK. Pirtobrutinib has previously displayed impressive efficacy findings and was well tolerated in patients with CLL/SLL in the phase 1/2 BRUIN trial (NCT03740529).1,3
In updated results from BRUIN, which is evaluating pirtobrutinib monotherapy in patients with B-cell malignancies who have undergone more than 2 prior therapies, evaluable patients with CLL/SLL (n = 139) achieved an overall response rate (ORR) of 63% (95% CI, 55%-71%). Patients experienced partial responses (50%), partial responses with lymphocytosis (14%), stable disease (32%), progressive disease (1%), and discontinuation of treatment (4%) while being treated with the agent. The median follow-up time was 6 months (range, 0.16-17.8+).3
The median age of patients with CLL/SLL (n = 170) was 69 years (range, 36-88). The median number of prior lines of therapy was 3 (range, 1-11). Most patients had received a prior BTK inhibitor (86%), an anti-CD20 antibody (90%), or chemotherapy (82%). Deletion of 17p, TP53 mutation, and unmutated IGHV were present in 25%, 30%, and 88% of patients, respectively.
In terms of tolerability, no dose limiting toxicities were reported, and the maximum tolerated dose was not reached. Common treatment-emergent adverse effects of any grade in the overall population (N = 323) included fatigue (20%), diarrhea (17%), and contusion (13%). Investigators determined 200 mg of pirtobrutinib daily as the recommended phase 2 dose.
The primary end point of BRUIN CLL-313 is progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia guidelines assessed by an independent review committee. Secondary end points consist of investigator-assessed PFS, ORR, overall survival, duration of response, safety and tolerability, and patient reported outcomes.
Study authors wrote that the results of the trial will be presented at a later date. Participation in the study could last up to 5 years.