Clinical Trial Testing Effectiveness of LOXO-305 in Mantle Cell Lymphoma Now Open to Patients

A phase 3 trial evaluating the safety and efficacy of the BTK inhibitor LOXO-305 in patients with previously treated mantle cell lymphoma is now open to patients across more than a dozen states.

A phase 3 clinical trial is currently underway and open for recruitment of patients with previously treated mantle cell lymphoma (MCL) to assess a Bruton’s tyrosine kinase (BTK) inhibitor called LOXO-305. The oral treatment works by blocking the activity that leads to the growth of B cells, causing the death of malignant B cells.

The clinical trial — called the BRUIN trial — is expected to enroll 500 patients, who are intended to be randomly given either LOXO-305 or the researcher’s choice of Imbruvica (ibrutinib), Calquence (acalabrutinib) or Brukinsa (zanubrutinib).

"MCL patients who have been treated with a covalent BTK inhibitor have very few therapeutic options, and outcomes are extremely poor. LOXO-305 has demonstrated a promising efficacy profile in these patients, a setting where we urgently need new therapies," said Dr. Michael Wang, Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center and presenting author of the study in a news release shared in late 2020, when updated data from phase 1/2 of the trial was presented.

In data presented at the 2020 American Society of Hematology Annual Meeting, LOXO-305 demonstrated and objective response rate — which measures the percentage of patients whose tumors shrunk as a result of treatment — of 52% in patients with MCL, including 14 complete and 15 partial responses. The median amount of time to an initial patient response to treatment was 1.8 months.

The most common side effects experienced by patients in the phase 1/2 portion were fatigue (20%) diarrhea (17%) and bruising (13%), regardless of disease type — as the trial also examined patients with chronic lymphocytic leukemia (CLL), small lymphocytic leukemia and Waldenstrom’s macroglobulinemia.

The trial is expected to be completed in February 2025. Its main goal is to compare progression-free survival (PFS; time until the patient’s disease progresses) between the treatment groups. Secondary objectives include event-free survival (amount of time after treatment ends that patients have a delay or event that the treatment was intended to prevent/delay), time to treatment failure, time to worsening of MCL-related symptoms, tolerability, ORR, duration of response (length of time a tumor continues to respond to treatment) and overall survival.

"LOXO-305 was designed to overcome some of the limitations seen with current BTK therapies and we believe the promising efficacy and tolerability data demonstrate its potential to be an important new treatment option for MCL patients,” said Dr. David Hyman, chief medical officer of Loxo Oncology at Lilly.

There are currently 84 study locations, including 18 U.S. states and multiple countries.

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