Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors

Study Overview
=================
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.

Official Title
-----------------
A Phase 1 Study of EP31670, a Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors

Conditions
-----------------
Castrate Resistant Prostate Cancer, NUT Carcinoma

Intervention / Treatment
-----------------
* Drug: EP31670


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Dose escalation/de-escalation will follow rules by employing the Bayesian optimal interval (BOIN) method.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>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<br>* EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.<br>* Other names: NEO2734;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | MTD is the highest dose level at which ≤30% of patients experienced DLTs during cycle 1. | Within 3 weeks (one cycle) of treatment | 
| Dose Limiting Toxicities (DLT) | DLT is any of the following adverse events (AEs) that occur during cycle 1. | Within 3 weeks (one cycle) of treatment | 
| Recommended Phase 2 Dose (RP2D) | RP2D will be the MTD | through study completion, an average of 1 year |