Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies

January 12, 2025 updated by: Epigenetix, Inc.

A Phase 1 Study of EP31670, a Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies

A Phase 1, first-in-human study of EP31670, a dual BET and CBP/p300 inhibitor in patients with targeted advanced solid tumors and Hematological Malignancies

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor which has demonstrated antitumor activity in in vitro and in vivo models of human cancer. This Phase I open-label, multi-center, dose-escalation study will assess the safety and determine the maximum tolerated dose of EP31670 administered orally in patients with castration-resistant prostate cancer, NUT midline carcinoma and other targeted advanced solid tumors as well as chronic myelomonocytic leukemia (CMML), myelofibrosis (MF) and other targeted hematological malignancies.

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Arizona
        • Principal Investigator:
          • Jeanne Palmer, MD
        • Contact:
          • Clinical Trials Referral Office
          • Phone Number: 855-776-0015
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
        • Principal Investigator:
          • James Foran, MD
        • Contact:
          • Clinical Trials Referral Office
          • Phone Number: 855-776-0015
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
        • Contact:
          • Atish Choudhury, MD
          • Phone Number: 877-442-3324
        • Contact:
          • Jia Luo, MD
          • Phone Number: 877-442-3324
        • Principal Investigator:
          • Atish Choudhury, MD
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
        • Contact:
          • Clinical Trials Referral Office
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Mrinal Patnaik, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Sarina A Piha-Paul, MD
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • University of Washington/Fred Hutchinson Cancer Center
        • Principal Investigator:
          • Michael Schweizer, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Part 1

  • Relapse or refractory castration-resistant prostate cancer (CRPC) following at least one anti-androgen regimen and a docetaxel-containing regimen OR
  • metastatic or unresectable NUT midline carcinoma for which standard curative or palliative measures do not exist; OR

Part 2

  • relapsed or refractory CMML following at least 4 cycles of hypomethylating agent-containing regimen or hydroxyurea unless demonstration of progression or intolerance;
  • advanced MF (intermediate or high-risk) following at least one JAK inhibitor-containing regimen or unsuitable candidates for JAK inhibitor treatments.

Part 3: advanced MF (intermediate or high-risk) with ≤10% blasts in peripheral blood who have not achieved an adequate response or have lost the response to a JAK inhibitor-containing regimen after being on treatment for at least 3 months.

Patients who have other types of relapsed or refractory solid tumors (Part 1) or hematological malignancies (Part 2) with pathological and/or biological features suggesting a potential benefit from dual BET and CBP/p300 inhibition may be enrolled after discussion with and approval from medical monitor and sponsor.

Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Life expectancy ≥ 3 months Evaluable disease

Adequate bone marrow function:

  • Hemoglobin ≥ 9.0 g/dL (Part 1)
  • Absolute neutrophil count (ANC) ≥ 1,500/dL (Part 1)
  • Platelet count ≥100,000/μL (Part 1) or ≥75,000/μL (Part 3)

Adequate renal function: Creatinine clearance (CLcr) ≥ 60 mL/min

Adequate liver function: total bilirubin ≤ 1.5 x ULN; alanine aminotransferase (ALT) or aspartate Aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN in patients with liver metastases

Internal normalized ratio for prothrombin time (INR) ≤ 1.2 in patients not receiving chronic anticoagulation

Four weeks from prior anti-cancer therapy including chemotherapy, immunotherapy, investigational anti-cancer therapy or 5 half-lives from targeted agents, radiation and have recovered from prior treatment toxicities to grade 1 or less.

Four weeks from major surgery.

For fertile men and women, agreement to use effective contraceptive methods duration of study participation and 4 weeks after the last dose of study drug.

Ability to understand and willingness to sign the informed consent form.

Exclusion Criteria:

  • New and progressive central nervous system (CNS) metastasis; patients with treated brain metastases are eligible if follow-up brain imaging at least 4 weeks after CNS-directed therapy shows no evidence of progression and the patient is neurologically stable
  • Corrected QT interval ≥470 msec
  • Uncontrolled concurrent illnesses including, but not limited to, ongoing active infection requiring intravenous antibiotics or antifungal agents, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would affect compliance with study requirements; patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of EP31670 are eligible for this trial
  • Pregnant or lactating women
  • Known history of hepatitis B, hepatitis C requiring antiviral treatment
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1
Patients will be assigned escalated dose according to BOIN design. The starting dose is 5 mg orally once a day for 7 consecutive days followed by 14 days of rest.
Drug: EP31670
EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.
Other Names:
  • NEO2734
Experimental: Part 2
Patients will be assigned escalated dose according to BOIN design. The starting dose is 20 mg orally once a day for 14 consecutive days followed by 14 days of rest.
Drug: EP31670
EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.
Other Names:
  • NEO2734
Experimental: Part 3
Patients will be assigned escalated dose according to BOIN design. The starting dose is 10 mg orally once a day for 14 consecutive days in combination with ruxolitinib or momelotinib followed by 14 days of rest according to the traditional 3 + 3 design by the modified Fibonacci sequence
Drug: EP31670
EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.
Other Names:
  • NEO2734

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: Within 3 weeks (one cycle) of treatment
MTD is the highest dose level at which ≤30% of patients experienced DLTs during cycle 1.
Within 3 weeks (one cycle) of treatment
Dose Limiting Toxicities (DLT)
Time Frame: Within 3 weeks (one cycle) of treatment
DLT is any of the following adverse events (AEs) that occur during cycle 1.
Within 3 weeks (one cycle) of treatment
Recommended Phase 2 Dose (RP2D)
Time Frame: through study completion, an average of 1 year
RP2D will be the MTD
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Epigenetix, Inc.

Investigators

  • Study Director: Judy Chiao, MD, Epigenetix, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2022

Primary Completion (Estimated)

May 1, 2025

Study Completion (Estimated)

May 1, 2025

Study Registration Dates

First Submitted

July 27, 2022

First Submitted That Met QC Criteria

August 3, 2022

First Posted (Actual)

August 4, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 12, 2025

Last Verified

September 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EP31670-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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