The administration of luxeptinib, a non-covalent inhibitor of BTK and FLT3 kinases, as a treatment for patients with relapsed/refractory (R/R) B-cell malignancies including chronic lymphocytic leukemia (CLL), small leukemia lymphoma (SLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL) yielded positive antitumor activity post-ibrutinib relapse and did not lead to greater pharmacokinetics (PK) exposure, according to findings from a phase 1a/b dose escalation study. 

At the 2022 ASH Annual Meeting and Exposition in New Orleans, LA, Felipe Samaniego, MD, MD Anderson Cancer Center, Houston, Texas, presented this data from a phase 1a/b study.

“Luxeptinib kills malignant B-cells insensitive to ibrutinib or venetoclax with concentrations in the nanomolar range and shows enhanced activity in combination with venetoclax,” Dr. Samaniego and colleagues stated as the impetus for this study.

A total of 35 patients were evaluated in the study as of June 30, 2022. The median age of the patients was 62. Of the participants, there were 16 patients with CLL/SLL, 7 with FL, 1 with Richter’s transformation lymphoma, 1 with marginal zone lymphoma (MZL), 2 with Waldenstrom macroglobulinemia, and 4 with MCL.  

All patients were administered luceptinib at doses ranging from 150mg to 900mg. The most common drug-related adverse events were decreased neutrophil count, decreased white blood cell count, decreased platelet count, diarrhea, anemia, and leukocytosis, indicating that the safety profile of luxeptinib is favorable.

A PK analysis showed that a dose of 750 mg provided sufficient plasma levels of luceptinib for sustained activity over multiple cycles. 20 patients who had at least 1 imaging study after starting treatment were eligible for response evaluations. Antitumor activity was observed in B-NHL subtypes and CLL-SLL patients who experienced relapse after ibrutinib treatment. 

Dr. Samaniego and colleagues concluded, “luxeptinib has a favorable safety profile in patients treated with 150 mg to 900 mg BID over multiple cycles,” adding, “enrollment of additional patients at dose level 6 (900 mg) is ongoing while the more bioavailable G3 formulation is being explored.”

Source: 

Samaniego F, Sadiq A, Mahadevan D, et al. A Phase 1a/b Dose Escalation Study of the BTK/FLT3 Inhibitor Luxeptinib in Patients with Relapsed or Refractory B-Cell Malignancies. Presented at ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 2893.