Abivertinib Produces Responses in Relapsed/Refractory Marginal Zone Lymphoma

Treatment with the irreversible BTK inhibitor abivertinib (Fujovee) led to responses and disease control in patients with relapsed/refractory marginal zone lymphoma (MZL), according to data from a phase 2a trial (NCT03060850) conducted in China.¹

Findings showed that patients with relapsed/refractory MZL (n = 27) who received multiple lines of prior therapy experienced an overall response rate (ORR) of 59.3%, which included a complete response rate of 11.1% and a partial response rate of 48.2%. Additionally, the disease control rate (DCR) was 92.6%. The median progression-free survival (PFS) and duration of response were not yet reached.

In light of these results, Sorrento Therapeutics has communicated with China’s National Medical Products Administration to discuss the design of a pivotal phase 3 registrational study to further investigative abivertinib in patients with relapsed/refractory MZL.

“We are very encouraged by the significant positive results of abivertinib for the treatment of relapsed/refractory 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,” Henry Ji, PhD, chairman and chief executive officer of Sorrento Therapeutics, stated in a news release.

Along with irreversibly binding to BTK, abivertinib is also a third-generation EGFR inhibitor.

In previously reported data from the phase 1 portion of the trial, which had a data cutoff date of August 28, 2020, abivertinib produced an ORR of 54.2% and a DCR of 95.8% across all doses examined in patients with relapsed/refractory B-cell lymphomas (n = 22).2 In patients treated with abivertinib at 200 mg twice per day (n = 11), the ORR was 81.8% with a DCR of 100%.

Patients treated at 200 mg per day, 150 mg twice per day, or 200 mg twice per day achieved an ORR of 63.6%, a DCR of 95.5%, and a median PFS of 19.7 months. Specifically in patients with MZL (n = 5), the ORR was 60%, with 3 patients experiencing a partial response; the DCR for these patients was 100%.

The phase 1 portion of the trial enrolled patients between 18 and 75 years of age with histologically confirmed 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, such as MZL, follicular lymphoma, Waldenström macroglobulinemia, and Burkitt lymphoma, were allowed to enroll in the dose-escalation portion of the research if they had relapsed/refractory disease after at least 1 prior line of systemic therapy.³

Other key inclusion criteria included having an ECOG performance status of 0 to 2; adequate heart, liver, lung, and renal function; and a life expectancy of more than 6 months.

Patients were excluded if they had central nervous system lymphoma, had prolymphocytic leukemia, Richter syndrome or suspected Richter syndrome, had primary mediastinal lymphoma, received prior treatment with a TKI or BTK inhibitor, received a monoclonal antibody within 3 months of first study treatment, underwent allogeneic stem cell transplant at any time, or underwent autologous stem cell transplant within 6 months of first study treatment.

The primary end point of phase 1 was to establish the recommended phase 2 dose. Secondary end points included maximum tolerated dose, ORR, and pharmacokinetics.

In the phase 1 portion of the study, the most common any-grade adverse effects (AEs) included neutropenia (58.6%), thrombocytopenia (44.8%), diarrhea (34.5%), anemia (34.5%), and increased alanine transaminase (34.5%). Grade 3 or 4 AEs reported in more than 10% of patients consisted of neutropenia (24.1%) and thrombocytopenia (17.2%).²

Treatment-related serious AEs were reported in 27.6% of evaluable patients (n = 8/29), and no deaths occurred during the treatment period. Serious AEs associated with first-generation BTK inhibitors such as ibrutinib (Imbruvica), such as serious bleeding, atrial fibrillation, bruising, and tumor lysis syndrome, were not reported with abivertinib.

Safety findings from the phase 2a portion of the trial showed that no instance of severe bleeding, arrhythmia, or hypertension occurred, and the agent was well tolerated.¹

References

1. Sorrento announces positive phase IIa study results of abivertinib for the treatment of relapsed/refractory marginal zone lymphoma (R/R MZL) and its plan for a pivotal phase III study. News release. Sorrento Therapeutics. July 5, 2023. Accessed July 5, 2023. https://www.biospace.com/article/releases/sorrento-announces-positive-phase-iia-study-results-of-abivertinib
2. Abivertinib – a franchise oral therapeutic for cancer, COVID-19 and autoimmune diseases. Sorrento Therapeutics. Accessed July 5, 2023. https://investors.sorrentotherapeutics.com/static-files/22057ad8-3752-4ee7-a4de-b84a055c0764
3. A phase I study of AC0010 in patients with CLL/​ SLL, MCL, DLBCL and other NHL. ClinicalTrials.gov. Updated February 1, 2019. Accessed July 5, 2023. https://clinicaltrials.gov/study/NCT03060850