A Phase IIa trial conducted in China demonstrated that treatment with the irreversible BTK inhibitor abivertinib (Fujovee) resulted in responses and disease control in patients with relapsed/refractory marginal zone lymphoma (MZL) on July 6.
In the study involving 27 patients with relapsed/refractory MZL who had received multiple lines of prior therapy, the overall response rate (ORR) was 59.3%, with a complete response rate of 11.1% and a partial response rate of 48.2%. The disease control rate (DCR) was 92.6%. The median progression-free survival (PFS) and duration of response were not yet determined.
Based on these positive results, Sorrento Therapeutics has engaged in discussions with China’s National Medical Products Administration regarding the design of a pivotal Phase III registrational study to further investigate abivertinib in patients with relapsed/refractory MZL.
“We are very encouraged by the significant positive results of Abivertinib for the treatment of R/R MZL, which would be a second indication of Abivertinib for cancer treatment in addition to the potential treatment of resistant EGFR mutant positive non-small cell lung cancer.”
– Dr. Henry Ji, Ph.D., Chairman and CEO of Sorrento
Apart from its irreversible binding to BTK, abivertinib also serves as a third-generation EGFR inhibitor.
Previously reported data from the Phase I portion of the trial showed an ORR of 54.2% and a DCR of 95.8% across all examined doses in patients with relapsed/refractory B-cell lymphomas. Patients treated with abivertinib at a dose of 200 mg twice per day demonstrated an ORR of 81.8% and a DCR of 100%.
Patients treated at various doses achieved an ORR of 63.6%, a DCR of 95.5%, and a median PFS of 19.7 months. Specifically, in patients with MZL, the ORR was 60%, with 3 patients experiencing a partial response, and the DCR was 100%.
The trial enrolled patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, or non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma. Patients with other types of non-Hodgkin lymphoma, including MZL, were allowed to participate in the study if they had relapsed/refractory disease after at least one prior line of systemic therapy.
Key inclusion criteria involved performance status, organ function, and life expectancy, while exclusion criteria included specific lymphoma subtypes, previous treatment with a TKI or BTK inhibitor, recent monoclonal antibody therapy, and certain stem cell transplant procedures.
In the Phase I part of the study, the main objective was to determine the recommended Phase II dose, while secondary objectives included assessing the maximum tolerated dose, objective response rate (ORR), and pharmacokinetics.
During the phase 1 portion, the most commonly observed adverse effects (AEs) of any grade were neutropenia (58.6%), thrombocytopenia (44.8%), diarrhea (34.5%), anemia (34.5%), and increased levels of alanine transaminase (34.5%). Grade 3 or 4 AEs that occurred in more than 10% of patients included neutropenia (24.1%) and thrombocytopenia (17.2%).
Treatment-related serious AEs were reported in 27.6% of patients evaluated (n = 8/29), and no deaths occurred during the treatment period. Notably, serious AEs commonly associated with first-generation BTK inhibitors like ibrutinib (Imbruvica), such as severe bleeding, atrial fibrillation, bruising, and tumor lysis syndrome, were not observed with abivertinib.
Safety findings from the Phase IIa segment of the trial indicated that there were no occurrences of severe bleeding, arrhythmia, or hypertension, and overall, the agent was well tolerated.
