Trial Title:
Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies
NCT ID:
NCT05488548
Condition:
Castrate Resistant Prostate Cancer
NUT Carcinoma
Chronic Myelomonocytic Leukemia
Myelofibrosis
Conditions: Official terms:
Hematologic Neoplasms
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
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)
Intervention:
Intervention type:
Drug
Intervention name:
EP31670
Description:
EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.
Arm group label:
Part 1
Arm group label:
Part 2
Arm group label:
Part 3
Other name:
NEO2734
Summary:
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
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic Arizona
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Investigator:
Last name:
Jeanne Palmer, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic Florida
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Investigator:
Last name:
James Foran, MD
Email:
Principal Investigator
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Atish Choudhury, MD
Phone:
877-442-3324
Contact backup:
Last name:
Jia Luo, MD
Phone:
877-442-3324
Investigator:
Last name:
Atish Choudhury, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Investigator:
Last name:
Mrinal Patnaik, MD
Email:
Principal Investigator
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rabia Khan
Phone:
713-563-4667
Email:
RKhan@MDAnderson.org
Investigator:
Last name:
Sarina A Piha-Paul, MD
Email:
Principal Investigator
Facility:
Name:
University of Washington/Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sheila Pagtakhan
Email:
phase1clinicaltrial@seattlecca.org
Investigator:
Last name:
Michael Schweizer, MD
Email:
Principal Investigator
Start date:
December 21, 2022
Completion date:
May 2025
Lead sponsor:
Agency:
Epigenetix, Inc.
Agency class:
Industry
Source:
Epigenetix, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05488548