Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors
- Conditions
- Castrate Resistant Prostate CancerNUT CarcinomaChronic Myelomonocytic LeukemiaMyelofibrosis
- Interventions
- Registration Number
- NCT05488548
- Lead Sponsor
- Epigenetix, Inc.
- Brief Summary
A Phase 1, first-in-human study of EP31670, a dual BET and CBP/p300 inhibitor in patients with targeted advanced solid tumors.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- 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
- patients who have other types of relapsed or refractory solid tumors 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 Absolute neutrophil count (ANC) ≥ 1,500/dL Platelet count ≥100,000/μL
- Adequate renal function:
Creatinine clearance (CLcr) estimated by Cockcroft-Gault Equation to be ≥ 60 mL/min. Estimated glomeruli filtration rate (eGRF) ≥ 60 mL/min may be used if provided by the testing laboratory
-
Adequate liver function
- Total bilirubin ≤ 1.5 x ULN except in patients diagnosed with Gilbert's disease for which direct bilirubin must be ≤ 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. Prostate cancer patients may continue androgen-deprivation therapy by luteinizing hormone-releasing hormone (LHRH) agonists.
-
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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 1 EP31670 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. Part 2 EP31670 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. Part 3 EP31670 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
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) Within 3 weeks (one cycle) of treatment MTD is the highest dose level at which ≤30% of patients experienced DLTs during cycle 1.
Dose Limiting Toxicities (DLT) Within 3 weeks (one cycle) of treatment DLT is any of the following adverse events (AEs) that occur during cycle 1.
Recommended Phase 2 Dose (RP2D) through study completion, an average of 1 year RP2D will be the MTD
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (6)
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Washington/Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Mayo Clinic Arizona🇺🇸Phoenix, Arizona, United StatesClinical Trials Referral OfficeContact855-776-0015Jeanne Palmer, MDPrincipal Investigator