Abivertinib Shows Promise Treating Marginal Zone Lymphoma

Abivertinib (Fujovee; Sorrento Therapeutics), an irreversible Bruton tyrosine kinase (BTK) inhibitor, produced promising results in patients with relapsed/refractory marginal zone lymphoma (MZL) in a recent phase 2a trial (NCT03060850).¹

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The study found that patients with relapsed/refractory MZL (n = 27) previously administered multiple lines of therapy experienced an overall response rate (ORR) of 59.3% with abivertinib, including a complete response rate of 11.1% and a partial response rate of 48.2%. Further, the disease control rate (DCR) was 92.6%, while median progression-free survival (PFS) and duration of response had not yet been reached.

In a press release, Sorrento Therapeutics said it plans to design a pivotal phase 3 registrational study to further analyze the use of abivertinib, a third-generation EGFR inhibitor, 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, said in the release.¹

A previously conducted phase 1 portion of the trial with a data cutoff date of August 28, 2020, showed that abivertinib produced an ORR of 54.2% and a DCR of 95.8% across all doses in patients with relapsed/refractory B-cell lymphomas (n = 22).² Further, the ORR was 81.8% with a DCR of 100% among those administered abivertinib at 200 mg twice daily (n = 11).

Patients administered 200 mg per day, 150 mg twice per day, or 200 mg twice per day showed an ORR of 63.6%, a DCR of 95.5%, and a median PFS of 19.7 months. Among patients with MZL (n = 5), the ORR was 60%, and 3 patients experienced a partial response with a DCR of 100%.

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. Individuals with other types of non-Hodgkin lymphoma, such as MZL, follicular lymphoma, Waldenström macroglobulinemia, and Burkitt lymphoma, were enrolled in the dose-escalation portion of the research if their disease was relapsed/refractory following at least 1 previous line of systemic therapy.³

Other key inclusion criteria were an ECOG performance status of 0 to 2, adequate heart, liver, lung, and renal function, as well as a life expectancy of more than 6 months. Exclusion criteria included central nervous system lymphoma, prolymphocytic leukemia, confirmed or suspected Richter syndrome, primary mediastinal lymphoma, prior use of a TKI or BTK inhibitor, administration of a monoclonal antibody within 3 months of initial study treatment, undergoing allogeneic stem cell transplant at any time or autologous stem cell transplant within 6 months of initial study treatment.

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

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

Treatment-related serious AEs were observed in 27.6% of evaluable patients (n = 8/29), with no deaths occurring during the treatment period. The phase 2a portion of the trial did not find any instances of severe bleeding, arrhythmia, or hypertension, 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