The BTK inhibitor pirtobrutinib recently demonstrated efficacy in a phase 1/2 trial of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously received BTK inhibitor treatment.1
Now, researchers are investigating pirtobrutinib in 4 ongoing phase 3 trials. In the BRUIN CLL-314 trial, researchers are comparing pirtobrutinib to ibrutinib in patients with CLL or SLL.2
With the BRUIN CLL-321 trial, researchers are comparing pirtobrutinib to either idelalisib plus rituximab or bendamustine plus rituximab in patients with CLL/SLL who previously received a BTK inhibitor.3
The BRUIN MCL-321 trial is designed to compare pirtobrutinib to investigator’s choice of BTK inhibitor in patients with previously treated, BTK inhibitor-naïve mantle cell lymphoma (MCL).4
And in the BRUIN CLL-322 trial, researchers are comparing pirtobrutinib plus venetoclax and rituximab to venetoclax and rituximab in previously treated patients with CLL or SLL.5
BRUIN CLL-314
The phase 3 BRUIN CLL-314 trial (ClinicalTrials.gov Identifier: NCT05254743) was designed to compare pirtobrutinib to ibrutinib in patients with CLL/SLL.2
This trial is set to enroll approximately 650 patients who either are treatment-naïve or were previously treated with other agents aside from BTK inhibitors. Patients cannot be taking warfarin or other vitamin K antagonists.
Patients will be randomly assigned to receive pirtobrutinib or ibrutinib. The primary endpoint is the overall response rate (ORR). Progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) are key secondary endpoints.
BRUIN CLL-321
The phase 3 BRUIN CLL-321 trial (ClinicalTrials.gov Identifier: NCT04666038) is designed to determine whether pirtobrutinib is superior to conventional therapy in patients with CLL or SLL who were previously treated with a BTK inhibitor.3
Investigators intend to enroll 250 patients with CLL/SLL who have no central nervous system (CNS) involvement or Richter transformation. Patients cannot have received allogeneic hematopoietic stem cell transplant (HSCT) or chimeric antigen receptor (CAR) T-cell therapy within 60 days prior to randomization.
The patients will be randomly assigned 1:1 to receive either pirtobrutinib or investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab. Patients in the control arm will be able to cross over to pirtobrutinib monotherapy if they experience disease progression.
The primary endpoint is PFS. Key secondary endpoints include ORR, OS, and time to next treatment.
BRUIN MCL-321
The phase 3 BRUIN MCL-321 study (ClinicalTrials.gov Identifier: NCT04662255) was designed to compare pirtobrutinib to investigator’s choice of BTK inhibitor in patients with previously treated, BTK inhibitor-naïve MCL.4
Investigators intend to enroll 500 patients. They must have had at least 1 prior line of therapy. They cannot have CNS involvement, and they cannot have received a BTK inhibitor, an allogeneic or autologous HSCT, or CAR T-cell therapy.
Patients will be randomly assigned 1:1 to receive either pirtobrutinib or investigator’s choice of ibrutinib, acalabrutinib, or zanubrutinib. The primary endpoint is PFS. ORR, EFS, and OS are key secondary endpoints.
BRUIN CLL-322
The phase 3 BRUIN CLL-322 trial (ClinicalTrials.gov Identifier: NCT04965493) was designed to assess whether adding pirtobrutinib to venetoclax plus rituximab can improve outcomes in patients with previously treated CLL or SLL.5
Approximately 600 patients will be randomly assigned 1:1 to receive venetoclax plus rituximab with or without pirtobrutinib. Eligible participants cannot have CNS involvement or Richter transformation. They cannot have received prior treatment with a BTK inhibitor, and they cannot have received allogeneic HSCT or CAR T-cell therapy within 60 days.
The study’s primary endpoint is PFS. Secondary endpoints include ORR, EFS, time to next treatment, and OS.
Disclosures: These trials are sponsored by Loxo Oncology, Inc., in collaboration with Eli Lilly and Company.
References
1. Mato AR, Woyach JA, Brown JR, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. Published online July 6, 2023. doi:10.1056/NEJMoa2300696
2. ClinicalTrials.gov. A study of pirtobrutinib (LOXO-305) versus ibrutinib in participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (BRUIN-CLL-314). NCT05254743. Accessed July 19, 2023.
3. ClinicalTrials.gov. Study of LOXO-305 versus investigator’s choice (IdelaR or BR) in patients with previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (BRUIN CLL-321). NCT04666038. Accessed July 19, 2023.
4. ClinicalTrials.gov. Study of BTK inhibitor LOXO-305 versus approved BTK inhibitor drugs in patients with mantle cell lymphoma (MCL) (BRUIN-MCL-321). NCT04662255. Accessed July 19, 2023.
5. ClinicalTrials.gov. A trial of pirtobrutinib (LOXO-305) plus venetoclax and rituximab (PVR) versus venetoclax and rituximab (VR) in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (BRUIN CLL-322). NCT04965493. Accessed July 19, 2023.
