FDA Grants Fast Track Designation to Abexinostat for Fourth-Line Follicular Lymphoma

The FDA has granted a fast track designation to abexinostat for the treatment of patients with relapsed or refractory follicular lymphoma in the fourth-line setting.¹

A potentially pivotal phase II trial of abexinostat monotherapy in patients with relapsed/refractory follicular lymphoma, known as the FORERUNNER study, is ongoing in the United States and Europe (NCT03600441).

Abexinostat is an oral hydroxamate-containing histone deacetylase (HDAC) inhibitor that is being developed by Xynomic Pharmaceuticals, after the company acquired the exclusive global rights for the drug in 2017.²Unlike other HDAC inhibitors, abexinostat has a unique pharmacokinetic profile and oral dosing schedule. The agent is given twice daily with 4 hours in between to allow for continuous exposure at concentration levels that can effectively kill tumor cells.³

A phase II study of abexinostat in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) showed a modest overall response rate (ORR), but a higher ORR was seen in patients with follicular lymphoma.

One hundred patients were treated with 80 mg abexinostat twice daily for 14 days of a 21-day cycle, which was given until progressive disease or unacceptable toxicity. All of the patients received at least 1 dose of abexinostat.

Eighty-seven patients were evaluable for efficacy and demonstrated an ORR of 28%, with complete responses seen in 5%. The ORR in patients with follicular lymphoma specifically was 56%, 40% in patients with T-cell lymphoma, and the ORR was 31% in patients with diffuse large B-cell lymphoma.

Grade ≥3 adverse events (AEs) were reported in 88% of patients and serious AEs in 73%. The most frequently reported grade ≥3 treatment-emergent AEs included thrombocytopenia in 80% of patients, neutropenia in 27%, and anemia in 12%.

The primary reason for discontinuation from the trial was due to progressive disease in 56% of patients and due to AEs in 25%.

The phase II trial in follicular lymphoma includes patients who have previously received at least 3 prior treatment regimens. Patients had to have grade 1-3a follicular lymphoma that has relapsed after or is refractory to their last line of therapy. Those who had grade 3b follicular lymphoma or transformation to diffuse large B-cell lymphoma were ineligible for the trial as well as those who had recently received an allogeneic or autologous stem cell transplant, a history of central nervous system lymphoma, cardiac impairment, or a history of other malignancies.

Abexinostat was administered 80 mg twice daily with 4 hours in between in a 1-week-on/1-week-off schedule in 28-day cycles.

Primary endpoints for the trial are the clinical effect of abexinostat in terms of complete and partial responses, and secondary endpoints include the duration of response, progression-free survival, clinical benefit rate, overall survival, adverse events, and the change in QTc interval.

The FDA previously granted a fast track designation to abexinostat in combination with pazopanib (Votrient) as a first- or second-line treatment for patients with renal cell carcinoma.

References

1. Xynomic Pharma Receives Fast-Track Designation from the US FDA for Abexinostat as 4L Therapy Treating Follicular Lymphoma [press release]. Xynomic Pharmaceuticals Holdings, Inc.: Shanghai, China; September 23, 2019. https://bit.ly/2m3xBxL. Accessed September 23, 2019.
2. Xynomic Pharma Has Acquired Worldwide Rights of Abexinostat [press release]. Xynomic Pharmaceuticals, Inc,: Cheyenne, Wyoming; February 24, 2017. https://prn.to/2l4eDH1. Accessed September 23, 2019.
3. Ribrag V, Kim WS, Bouabdallah R, et al. Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study.Haematologica. 2017;102(5):903-909. doi: 10.3324/haematol.2016.154377.