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

Lisa Astor
Published Online:4:46 PM, Mon September 23, 2019
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 2017.2 Unlike 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.
  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.

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