Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies
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
- Castrate Resistant Prostate Cancer
- NUT Carcinoma
- Chronic Myelomonocytic Leukemia
- Myelofibrosis
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
| Arm | Description | Assigned 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. |
|
|
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. |
|
|
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 |
|
Recruiting Locations
Phoenix, Arizona 85054
Clinical Trials Referral Office
855-776-0015
Jacksonville, Florida 32224
Clinical Trials Referral Office
855-776-0015
Boston, Massachusetts 02215
Atish Choudhury, MD
877-442-3324
Rochester, Minnesota 55905
Clinical Trials Referral Office
855-776-0015
Houston, Texas 77030
Seattle, Washington 98109
More Details
- Status
- Recruiting
- Sponsor
- Epigenetix, Inc.
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.