Novel BET Inhibitor PLX51107 for Steroid-Refractory Acute GVHD

NCT04910152 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: OSU-20273NCI-2021-02282R01CA252469
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the side effects of PLX51107 in treating steroid-refractory acute graft versus host disease (GVHD). PLX51107 is a novel, potent non-benzodiazepine structured small molecule BET inhibitor with a unique binding mode selective for BRD4 inhibition and a more tolerable side effect profile. PLX51107 may work better in treating steroid-refractory acute GVHD.

Conditions

Acute Graft Versus Host Disease; Steroid Refractory Graft Versus Host Disease

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  Up to 28 days

• Incidence of Adverse Events Grade 3 and 4

  Adverse events by grade will be summarized. The occurrence of grade 3+ adverse events according to Common Terminology Criteria for Adverse Events will be summarized as well. Adverse events will initially be reviewed regardless of attribution, but also according to whether adverse events are possibly, probably, or definitely related to treatment.

  Up to 6 months

Secondary Outcomes (3)

• Complete Response (CR)

  At day 28

• Overall Response Rate

  At day 28

• Non-relapse Mortality (NRM)

  From the date of starting PLX51107 to date of death with the competing risk as death due to disease, assessed at 6 months

Other Outcomes (1)

• Pharmacokinetics (PK) Analysis

  Up to 6 months

Study Arms (1)

Treatment for aGVHD (BRD4 inhibitor PLX51107)

EXPERIMENTAL

Patients receive BRD4 inhibitor PLX51107 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: BRD4 Inhibitor PLX51107

Interventions

BRD4 Inhibitor PLX51107 DRUG

Given PO

Also known as: PLX 51107, PLX-51107, PLX51107

Treatment for aGVHD (BRD4 inhibitor PLX51107)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years at the time of signing informed consent
• Steroid-refractory acute GVHD as defined as progression of acute (a)GvHD within 3-5 days of therapy onset with \>= 2 mg/kg/day of prednisone equivalent OR failure to improve within 5-7 days of treatment initiation with \> 1-2 mg/kg/day of prednisone equivalent OR incomplete response after more than 28 days of immunosuppressive treatment including steroids
• Recipients of ablative and reduced-intensity conditioning regimens
• Recipients of human leukocyte antigen (HLA)-matched related and unrelated, 1-allele mismatched, haploidentical, or umbilical cord blood donor grafts
• Prior lines of therapy for treatment of steroid-refractory acute GVHD are allowed. However, exposure to investigational therapies for the treatment of GVHD must be \> 14 days or 5 half-lives (whichever is shorter) of first administration of study drug. For patients treated with ruxolitinib for the treatment of acute GVHD, ruxolitinib must be discontinued by at least one day prior to initiation of PLX51107
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
• Absolute neutrophil count \>= 1.0 x 10\^9/L for 3 consecutive days). Use of growth factor support is allowed
• Platelet count \>= 50 x 10\^9/L without transfusion support for 2 consecutive days
• Women of child-bearing potential must have a negative serum pregnancy test at Screening and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-child-bearing potential may be included if they are either surgically sterile or have been postmenopausal for \>= 1 year
• Fertile men must agree to use an effective method of birth control during the study and for up to 6 months after the last dose of study drug

You may not qualify if:

• Prior exposure to a bromodomain inhibitor
• Evidence of chronic GVHD
• Evidence of active relapse of disease
• Exposure to other investigational or anti-cancer therapies (not for GVHD) within 28 days or 5 half-lives (whichever is shorter) of first administration of study drug
• Active, uncontrolled bacterial, fungal, or viral infection
• Known or suspected allergy to the study drug
• Clinically significant cardiac disease, defined as:
• Clinically significant cardiac arrhythmias, including bradyarrhythmia, and/or a need for anti-arrhythmic therapy (excluding beta blockers or digoxin). Individuals with controlled atrial fibrillation are not excluded
• Fridericia-corrected QT interval (QTcF) \>= 450 ms (male) or \>= 470 ms (female) at screening
• History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association Class II. Subjects must not have unstable angina (angina symptoms at rest) or experienced either new-onset angina within the last 3 months or myocardial infarction (MI) within the last 6 months unless it was due to the underlying disease and there has been appropriate revascularization. Individuals with ambiguous troponin levels that are not diagnostic of an MI should be discussed with the principal investigator (PI) prior to enrollment
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication (except for catheter-related venous thrombosis
• Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
• Active thrombotic microangiopathy (TMA)
• Women who are either pregnant or breast feeding
• Measured or calculated (Cockcroft-Gault formula) creatinine clearance (CrCl) \< 45 mL/min

Sponsors & Collaborators

• Hannah Choe, MD: lead
• Plexxikon: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Interventions

PLX51107

Results Point of Contact

• Title: Dr. Hannah Choe
• Organization: The Ohio State University Comprehensive Cancer Center

Hannah.choe@osumc.edu

614-293-3196

Study Officials

• Hannah Choe, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 24, 2021
• First Posted: June 2, 2021
• Study Start: April 19, 2022
• Primary Completion: September 28, 2023
• Study Completion: September 28, 2023
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)