Castrate Resistant Prostate Cancer, Chronic Myelomonocytic Leukemia, Myelofibrosis, NUT Carcinoma
Conditions
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 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.
Interventions
DRUGEP31670
EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.
Sponsors
Epigenetix, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
Primary ContactJudy Chiao, MD
Outcome results
None listed