FDA Approves Pirtobrutinib for Previously Treated CLL/SLL

The FDA has granted an accelerated approval to pirtobrutinib (Jaypirca) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor.¹

The approval is based on overall response rate (ORR) and duration of response (DOR) data from the open-label, single-arm, multicohort, phase 1/2 BRUIN trial (NCT03740529). Among 108 patients with CLL/SLL, the ORR was 72% (95% CI, 63%-80%), all of which were partial responses. The median time to response was 3.7 months (range, 1.7-27.9), and the median DOR was 12.2 months (95% CI, 9.3-14.7).

Continued approval for this indication may be dependent on confirmation of clinical benefit in a confirmatory trial such as the phase 3 BRUIN CLL-321 trial (NCT04666038).

"Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of [pirtobrutinib] a meaningful advance and much-needed new treatment option for these patients," William G. Wierda, MD, PhD, professor, medical director, and CLL section head for the Department of Leukemia at The University of Texas MD Anderson Cancer Center, stated in a news release. "[Pirtobrutinib] offers a new treatment option and different approach to targeting BTK, providing clinical benefit for a high proportion of patients with CLL or SLL in the BRUIN phase 1/2 trial whose disease progressed following treatment with a covalent BTK inhibitor and with a BCL2 inhibitor."

In January 2023, the FDA approved pirtobrutinib for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) following at least 2 lines of systemic therapy, including a BTK inhibitor.²

"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," Jacob Van Naarden, chief executive officer, Loxo@Lilly, added. "These first two 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."¹

In the CLL/SLL cohort, patients received 200 mg of pirtobrutinib once daily until disease progression or unacceptable toxicity. Patients with active central nervous system (CNS) involvement by lymphoma or allogeneic hematopoietic stem cell transplantation (HSCT) within 60 days were excluded from enrollment.

All patients in the CLL/SLL cohort had received at least 2 prior lines of therapy, including a BTK inhibitor and BCL2 inhibitor. Patients in the efficacy-eligible population had received a median of 5 prior lines of therapy (range, 2-11). The most common BTK inhibitors that had been received were ibrutinib (Imbruvica; 97%), acalabrutinib (Calquence; 9%), and zanubrutinib (Brukinsa; 0.9%). Seventy-seven percent (77%) of patients discontinued the last BTK inhibitor for refractory or progressive disease.

Regarding safety in the CLL/SLL population (n = 110), adverse effects (AEs) that led to permanent treatment discontinuation in more than 1% of patients in the trial included second primary malignancy, COVID-19, and sepsis. Serious AEs occurred in 56% of patients who received pirtobrutinib. Serious As that occurred in at least 5% of patients included pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%).

"The treatment landscape for CLL has been dramatically improved by the introduction of covalent BTK inhibitors and BCL2 inhibitors. However, most patients will unfortunately relapse eventually," Brian Koffman, MD, chief medical officer and executive vice president at the CLL Society, said. "Pirtobrutinib's approval gives patients a much-needed option and brings forward new possibilities as they continue their treatment journey."

References

1. Jaypirca (pirtobrutinib) now approved by U.S. FDA for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who have received at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. News release. Eli Lilly and Company. December 1, 2023. Accessed December 1, 2023. https://www.prnewswire.com/news-releases/jaypirca-pirtobrutinib-now-approved-by-us-fda-for-the-treatment-of-adult-patients-with-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-who-have-received-at-least-two-lines-of-therapy-including-a-btk-inhibitor-and--302003695.html#:~:text=INDIANAPOLIS%2C%20Dec.%201%2C%202023,(CLL%2FSLL)%20who%20have
2. US FDA approves Jaypirca (pirtobrutinib), the first and only non-covalent (reversible) BTK inhibitor, for adult patients with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a BTK inhibitor. News release. Loxo@Lilly. January 27, 2023. Accessed January 27, 2023.