Purpose

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

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Intervention Model Description
Dose escalation/de-escalation will follow rules by employing the Bayesian optimal interval (BOIN) method for Part 1 and Part 2 and traditional 3+ 3 by modified Fibonacci sequence for Part 3
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Mayo Clinic Arizona
Phoenix, Arizona 85054
Contact:
Clinical Trials Referral Office
855-776-0015

Mayo Clinic Florida
Jacksonville, Florida 32224
Contact:
Clinical Trials Referral Office
855-776-0015

Dana Farber Cancer Institute
Boston, Massachusetts 02215
Contact:
Atish Choudhury, MD
877-442-3324

Mayo Clinic Rochester
Rochester, Minnesota 55905
Contact:
Clinical Trials Referral Office
855-776-0015

The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
Contact:
Rabia Khan
713-563-4667
RKhan@MDAnderson.org

University of Washington/Fred Hutchinson Cancer Center
Seattle, Washington 98109
Contact:
Harini Ramachandran
phase1clinicaltrial@seattlecca.org

More Details

Status
Recruiting
Sponsor
Epigenetix, Inc.

Study Contact

Judy Chiao, MD
(561) 865-6098
studies@epigenetix.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.