Eli Lilly has chalked up another victory in the chronic lymphocytic leukemia (CLL) space, as its BTK inhibitor Jaypirca delivered its fourth positive phase 3 readout in the blood cancer.
Monday, Lilly said its phase 3 Bruin CLL-322 trial in patients with previously treated CLL or small lymphocytic lymphoma (SLL) has met its primary endpoint. In an industry first, the study showed that adding Jaypirca to a fixed-duration regimen of venetoclax and rituximab significantly extended progression-free survival (PFS) compared with the standard combo alone.
As Lilly pointed out, Bruin CLL-322 is the first phase 3 in CLL to utilize and outperform a venetoclax-based regimen. Roche and AbbVie sell venetoclax, an oral BCL-2 inhibitor, under the brand name Venclexta.
“Bruin CLL-322 was an ambitious trial, building on an effective regimen, and these results outperformed our expectations,” Jacob Van Naarden, president of Lilly Oncology, said in an April 13 release.
Besides hitting its PFS goal, the trial also showed an overall survival trend in favor of the Jayirca combo regimen, although this secondary endpoint was not yet mature, according to Lilly. In addition, rates of adverse events and treatment discontinuations were similar between the two arms, the company added.
Based on the data, Lilly said it plans to ask regulators for an approval this year.
BTK inhibitors have been approved for previously treated CLL for some time. BeOne Medicines’ market-leading BTK drug Brukinsa scored an FDA label expansion in the indication in late 2023 after beating AbbVie and Johnson & Johnson’s first-to-market Imbruvica on PFS in second-line CLL.
As covalent BTK drugs like Brukinsa, Imbruvica and AstraZeneca’s Calquence are increasingly given upfront to treatment-naïve patients, a venetoclax-based regimen is usually reserved as a standard second-line option because patients cannot be retreated with a covalent BTK inhibitor for a second time.
Even among patients who receive Venclexta in the first line, some doctors may choose to rechallenge their cancer with a venetoclax-based regimen—either by switching the combo partner or by adding another treatment.
Jaypirca, a non-covalent BTK, recently emerged as a new second-line option, but its prior FDA approval in the space was based on a phase 3 study against investigator’s choice of rituximab and either Gilead Sciences’ Zydelig or bendamustine. The phase 3 Bruin CLL-321 trial showed that Jaypirca alone significantly improved PFS versus those combos.
In that study, Jaypirca was used indefinitely until disease progression or unacceptable toxicity, which can be a disadvantage compared to a time-limited venetoclax-based regimen, especially when there’s no head-to-head comparison showing which is more efficacious. But that dynamic has changed with the latest readout.
“For doctors and patients who prefer a time-limited approach, these Bruin CLL-322 data demonstrate that the addition of Jaypirca could further extend the duration of benefit in second-line CLL,” Van Naarden said.
Jaypirca’s latest PFS results were consistent across key subgroups and regardless of whether patients had previously received a covalent BTK inhibitor, Lilly said.
Alongside Bruin CLL-321 and -322, Lilly also counts -313 and -314, which include treatment-naïve CLL patients, among positive phase 3 studies that Jaypirca has produced.
Jaypirca is not the first BTK drug to succeed in a fixed-duration regimen. In February, AZ’s Calquence-Venclexta cocktail became the first all-oral, fixed-duration regimen approved in the U.S. for first-line CLL.
Meanwhile, a phase 3 trial of BeOne’s fixed-duration pairing of Brukinsa and the company’s next-generation BCL-2 drug sonrotoclax in previously untreated CLL recently completed enrollment.