First Patient Dosed in Trial Testing Abexinostat-Imbruvica Combo for Advanced Lymphomas

Xynomic Pharma has initiated patient dosing in a Phase 1/2 trial testing its investigational therapy abexinostat, in combination with Imbruvica (ibrutinib), as a treatment for people with mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) who failed prior lines of treatment, the company announced.

The trial (NCT03939182), ongoing at the Memorial Sloan Kettering Cancer Center, is currently recruiting participants. More information on enrollment can be found here.

Imbruvica, jointly developed and commercialized by Janssen and Pharmacyclics, is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor. BTK helps B-cells stay alive and divide, but by blocking these signals, Imbruvica stops or slows the progression of cancer.

The treatment is approved for multiple blood cancers, including previously-treated mantle cell lymphoma. However, only 60% to 70% of patients respond, and those responses last only a median of 18 months.

Abexinostat is an oral inhibitor, or blocker of histone deacetylase (HDAC) enzymes. These enzymes cause a remodeling in the chromosomes, and increase the amount of tumor suppressor genes being produced. These genes then prevent the growth and division of cancer cells.

Interestingly, prior clinical trials have shown promising response rates in both MCL and DLBCL patients treated with abexinostat. Preclinical studies suggested that combining abexinostat with Imbruvica leads to better responses than either agent used alone.

Thus, Memorial Sloan Kettering researchers designed a clinical trial to study a combination of abexinostat and Imbruvica in previously treated MCL and DLBCL patients.

The study will enroll 40 participants, and includes a dose escalation phase, followed by a dose expansion part. In the first part, participants will receive one of two abexinostat doses — 30 mg/m² or 45 mg/m² — along with Imbruvica, to determine the optimal dose for further testing. Both medicines will be given orally.

Then, in the second part, participants will receive the Imbruvica plus abexinostat at the determined dose, to continue studying its safety and preliminary signs of efficacy.

Xynomic also is preparing two Phase 2 trials in China to explore the safety and efficacy of abexinostat as a third-line therapy for DLBCL and follicular lymphoma, another type of non-Hodgkin’s lymphoma.

Abexinostat also is being evaluated as a fourth-line therapy for people with follicular lymphoma in the FORERUNNER Phase 2 trial (NCT03600441). The trial is running across several sites in the U.S, but may expand to include clinical sites in Europe and China.