Abexinostat for Follicular Lymphoma

(FORERUNNER Trial)

Not currently recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Xynomic Pharmaceuticals, Inc.

Disqualifiers: Grade 3b lymphoma, CNS lymphoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: 28-day cycles, up to 100 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of abexinostat, an experimental drug, in treating follicular lymphoma that has returned or not responded to at least three previous treatments. Participants will take abexinostat tablets twice a day for a week, followed by a week off, in a repeated cycle. The trial seeks individuals diagnosed with follicular lymphoma who have faced treatment challenges and need further care, particularly if their condition has relapsed. As a Phase 2 trial, the research focuses on measuring how well the treatment works in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that abexinostat is likely to be safe for humans?

Research has shown that abexinostat has been tested in several studies to assess its safety in humans. In studies involving patients with relapsed or hard-to-treat lymphomas, the treatment was generally well-tolerated. For instance, a study with 55 patients administered abexinostat on a schedule similar to this trial—one week on, one week off—and most patients managed it well.

Common side effects included tiredness and low blood counts, but these were mostly mild to moderate. Another study with Chinese patients found similar safety results. These studies suggest that abexinostat can be safe for people with conditions like follicular lymphoma. While side effects may occur, they are usually not severe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for follicular lymphoma involve chemotherapy or monoclonal antibodies, like rituximab. However, Abexinostat is unique because it works as a histone deacetylase inhibitor, which is a different mechanism of action. This means it targets the cancer cells by altering their DNA expression, potentially making them more susceptible to other treatments. Researchers are excited about Abexinostat because it is administered orally, making it more convenient than some traditional intravenous therapies. Additionally, its "one week on, one week off" dosage schedule might help reduce side effects and improve patient quality of life.

What evidence suggests that abexinostat might be an effective treatment for follicular lymphoma?

Research has shown that abexinostat, which participants in this trial will receive, may help treat relapsed or hard-to-treat follicular lymphoma. Studies have found that abexinostat, a drug affecting certain proteins in cells, can work against lymphoma cells. In previous studies, patients with follicular lymphoma who took abexinostat experienced positive results, with some seeing their tumors shrink. Additionally, early research has demonstrated that abexinostat can kill cancer cells, including those from follicular lymphoma. These findings suggest that abexinostat could be a promising treatment option for patients with this challenging condition. ^{1 4 6 7 8}

Who Is on the Research Team?

Connie Batlevi, MD, PhD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with Grade 1, 2, or 3a follicular lymphoma that's come back or didn't respond to at least three prior treatments. Participants must use effective birth control and not breastfeed or donate sperm during the study and for 90 days after. Exclusions include central nervous system lymphoma history, previous abexinostat treatment, cardiac issues, recent investigational drugs, other cancers within three years (except skin cancer), Grade 3b lymphoma or large B-cell transformation.

Inclusion Criteria

I am a woman who cannot become pregnant because I am postmenopausal or have been surgically sterilized.

My lymphoma is confirmed as Grade 1, 2, or 3a.

I agree not to donate sperm from the start of the study until 90 days after the last dose.

Exclusion Criteria

Has received any investigational medication within 30 days or 5 half-lives prior to Day 1, whichever is longer

I have been cancer-free from other types of cancer for over 3 years.

I have a heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abexinostat 80 mg BID in a 'one week on, one week off' schedule

28-day cycles, up to 100 months

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 months

What Are the Treatments Tested in This Trial?

Interventions

• Abexinostat

Trial Overview

The trial tests Abexinostat in patients with relapsed/refractory follicular lymphoma following multiple therapies. Patients will take Abexinostat orally twice daily on a schedule of one week on followed by one week off.

How Is the Trial Designed?

Group I: Abexinostat Experimental Treatment 1 Intervention

Abexinostat tablets will be administered orally at 80 mg (4 × 20 mg tablets) BID (twice a day) 4 hours apart for 7 days in a "one week on, one week off" schedule (on Days 1 to 7 and Days 15 to 21 of each 28-day cycle).

Who Is Running the Clinical Trial?

Xynomic Pharmaceuticals, Inc.

Lead Sponsor

Trials

11

Recruited

1,200+

Published Research Related to This Trial

In a phase II trial involving 29 patients with untreated follicular lymphoma, rituximab combined with fludarabine and mitoxantrone achieved a high overall response rate of 100% and a complete remission rate of 66%, with notably higher remission rates in female patients.

Pharmacokinetic analysis revealed significant variability in rituximab serum concentrations, which correlated with treatment outcomes; specifically, higher serum levels were linked to better remission quality and longer progression-free survival, suggesting that dosing may need to be tailored based on patient characteristics like gender and bone marrow infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Jäger, U., Fridrik, M., Zeitlinger, M., et al.[2021]

The chimeric anti-CD20 monoclonal antibody IBI301 was well tolerated in nine Chinese patients with CD20(+) B-cell non-Hodgkin's lymphoma, with no severe adverse events or dose-limiting toxicities reported during the study.

IBI301 effectively eliminated peripheral CD20-expressing B cells in all patients, indicating its potential efficacy in targeting B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. Jiang, B., Qi, JY., Sun, MY., et al.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12123727/

Safety, pharmacokinetics, and efficacy of abexinostat, an ...

Second-line and subsequent therapy and outcomes for follicular lymphoma in the United States: data from the observational National LymphoCare ...

2.

ashpublications.org

ashpublications.org/blood/article/120/21/55/86965/A-Phase-II-Multicenter-Study-of-the-Histone

A Phase II Multicenter Study of the Histone Deacetylase ...

Abexinostat (PCI-24781) is a novel oral pan-HDACi that has previously demonstrated potent preclinical activity in lymphoma cell lines and ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5477609/

Safety and efficacy of abexinostat, a pan-histone ...

Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study.

4.

aacrjournals.org

aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-15-0624/2107838/1078-0432_ccr-15-0624v1.pdf

Research Article Cancer Therapy: Clinical A phase I/II ...

Phase II evaluated abexinostat at the maximum tolerated dose in 30 patients with relapsed/refractory follicular lymphoma (FL) or mantle cell lymphoma (MCL).

5.

sciencedirect.com

sciencedirect.com/topics/medicine-and-dentistry/abexinostat

Abexinostat - an overview

Preclinical data demonstrate cytotoxic activity in B lymphoid tumor cell lines, human follicular lymphoma, myeloma, and CLL cells, as well as synergism with ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0006497118563229

Abexinostat (S78454/PCI-24781), an Oral Pan-Histone ...

The primary objective of the Phase I was to assess the safety profile and to determine the recommended Phase 2 dose (RP2D) as well as the optimal administration ...

7.

bmccancer.biomedcentral.com

bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14370-y

Safety, pharmacokinetics, and efficacy of abexinostat, an ...

This phase 1 study investigate the safety, pharmacokinetics (PK), and efficacy of abexinostat in Chinese patients with relapsed/refractory (r/r) B cell NHL.

8.

aacrjournals.org

aacrjournals.org/clincancerres/article/22/5/1059/79866/A-Phase-I-II-Multicenter-Open-Label-Study-of-the

A Phase I/II Multicenter, Open-Label Study of the Oral Histone ...

The phase I study examined safety, pharmacokinetics, and pharmacodynamics of different abexinostat treatment schedules in multiple lymphoma subtypes. Following ...