Eli Lilly has scored another victory in chronic lymphocytic leukemia (CLL) with the company’s BTK inhibitor Jaypirca showing its fourth positive Phase 3 result in a blood cancer.
Lilly announced Monday that its Phase 3 Bruin CLL-322 trial in patients with previously treated CLL or small lymphocytic lymphoma (SLL) met its primary endpoint. This industry-first study showed that the addition of Jpirca to a fixed-duration regimen of venetoclax and rituximab significantly prolonged progression-free survival (PFS) compared to the standard combination therapy alone.
As Lilly noted, Bruin CLL-322 is the first Phase 3 to utilize and surpass a venetoclax-based regimen in CLL. Roche and AbbVie market venetoclax, an oral BCL-2 inhibitor, under the brand name Venclexta.
“Bruin CLL-322 was an ambitious trial based on an effective regimen, and these results exceeded our expectations,” said Jacob Van Naarden, president of Lilly Oncology, in an April 13 release.
In addition to meeting the PFS goal, Lilly said the trial also showed an overall survival trend favoring the Jyrca combination, although this secondary endpoint was not yet mature. Additionally, the incidence of adverse events and treatment discontinuation rates were similar in both groups, the company added.
Based on the data, Lilly said it plans to seek regulatory approval later this year.
BTK inhibitors have been approved for previously treated CLL for some time. B-One Medicines’ market-leading BTK drug Brukinsa beat AbbVie and Johnson & Johnson’s first-to-market Imbruvica in PFS in second-line CLL and won FDA expansion for that indication in late 2023.
As covalent BTK drugs such as Brukinsa, Imbruvica, and AstraZeneca’s Calquence are increasingly being prepaid to previously untreated patients, patients are unable to undergo a second retreatment with a covalent BTK inhibitor, usually reserving venetoclax-based regimens as the standard second-line option.
Even among patients receiving first-line venetoclax, some physicians choose to re-challenge their cancer with a venetoclax-based regimen by changing combination partners or adding another therapy.
Jypirka, a non-covalent BTK, has recently emerged as a new second-line drug, but previous FDA approval in this area was based on phase 3 trials of rituximab and researchers’ choice of either Gilead Sciences’ Zydelig or bendamustine. The Bruin CLL-321 Phase 3 trial showed that Jaypirca alone significantly improved PFS compared to their combination.
In that study, Jpirca was used indefinitely until disease progression or unacceptable toxicity, which may have a disadvantage over limited-duration venetoclax-based regimens, especially in the absence of a direct comparison to show which is more effective. But that dynamic has changed with the latest announcement.
“For physicians and patients who prefer a time-limited approach, these Bruin CLL-322 data demonstrate that the addition of Jypirca may further extend the duration of response in second-line CLL,” Van Naarden said.
Jaypirka’s latest PFS results were consistent across major subgroups, regardless of whether patients had previously received a covalent BTK inhibitor, Lilly said.
In addition to Bruin CLL-321 and -322, Lilly also counts -313 and -314, which include untreated CLL patients, among positive Phase 3 trials produced by Jaypirka.
Jaypirka is not the first BTK drug to be successful in a fixed-duration regimen. In February, AZ’s Calquence-Venclexta cocktail became the first all-oral fixed-duration regimen approved in the United States for first-line CLL.
Meanwhile, a Phase 3 trial of BeOne’s fixed-duration combination therapy of Brukinsa and the company’s next-generation BCL-2 drug Sonlotoclax in previously untreated CLL recently completed enrollment.
