Jaypirca Shows Improvements Over Imbruvica in CLL/SLL

Treatment with Jaypirca (pirtobrutinib) demonstrated positive topline results from the phase 3 BRUIN CLL-314 clinical trial when compared with Imbruvica (ibrutinib) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), according to a news release from Eli Lilly and Company.

In the clinical trial, Jaypirca met the primary end point of the study by showing a favorable overall response rate with evidence suggesting better outcomes compared with Imbruvica in patients had been previously treated but were BTK inhibitor-naïve, the news release continued.

In addition, early progression-free survival data show a trend favoring Jaypirca.

BRUIN CLL-314 trial is the first-ever head-to-head phase 3 study to compare covalent BTK inhibitor treatment and include treatment-naïve patients within the treatment group This subgroup of 225 patients had the longest follow-up and showed a notably longer progression-free survival benefit with Jaypirca versus Imbruvica, as per the release.

Patients treated with Jaypirca had a higher overall response rate, meaning more patients’ cancers shrank or disappeared compared with the other treatment. This difference was statistically significant, with a p-value below 0.05, indicating the result is unlikely due to chance.

"We launched the Jaypirca randomized development program with an ambitious suite of clinical trials, including head-to-head studies against modern standards of care and examinations of patient populations that reflect real world use, such as BTK inhibitor-pretreated patients," Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in the news release. "These data mark the second positive phase 3 study in the program, as we continue to build evidence supporting the potential role of Jaypirca in treating people with CLL/SLL and hopefully enabling future regulatory approvals that allow physicians to use the medicine in various disease settings, whether treatment-naïve or BTK inhibitor-pretreated."

A formal analysis to determine if Jaypirca extends the time patients live without their cancer worsening is planned for a future update. Regarding side effects, the safety profile of Jaypirca in the BRUIN CLL-314 study was consistent with earlier trials. Detailed results will be shared at a medical congress later in 2025, according to the release.

Furthermore, these findings add to earlier positive results from the BRUIN Phase 1/2 trial and the Phase 3 BRUIN CLL-321 study, which was the first randomized controlled trial focused solely on patients previously treated with covalent BTK inhibitors. The BRUIN CLL-313 Phase 3 trial, comparing Jaypirca to chemoimmunotherapy in patients newly diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma, is expected to report results later in 2025. Combined with BRUIN CLL-314 data, these studies will support regulatory filings worldwide.

BRUIN CLL-314 is a Phase 3, randomized study comparing Jaypirca with Imbruvica in people with chronic lymphocytic leukemia or small lymphocytic lymphoma who have not received prior treatment or have never taken a BTK inhibitor. The trial is expected to enroll 650 participants, who will be randomly assigned to receive either Jaypirca (200 milligrams once daily) or Imbruvica (420 milligrams once daily), both taken by mouth.

The main goal is to measure how many patients respond to treatment. Other key goals include tracking how long the cancer stays under control, how long responses last, overall survival, time to next treatment, side effects, and quality of life.

Jaypirca is a targeted treatment designed to block a protein called BTK, which plays a role in several types of blood cancers. It works in a reversible way and is over 300 times more selective for BTK than most other proteins it was tested against in lab studies. Jaypirca is an oral medicine approved in the U.S. and comes in 100 milligram or 50 milligram tablets. It is taken once daily as a 200-milligram dose, with or without food, until the cancer grows or side effects become too serious.

Reference

1. “Lilly's Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) BTK inhibitor, met its primary endpoint in a head-to-head Phase 3 trial versus Imbruvica (ibrutinib) in CLL/SLL,” Eli Lilly. Press Release. July 29.

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