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

• ClinicalTrials.gov Identifier: NCT05488548
• Recruitment Status: Recruiting
• First Posted: August 4, 2022
• Last Update Posted: February 16, 2023
• Sponsor: Epigenetix, Inc.
• Information provided by (Responsible Party): Epigenetix, Inc.

Tracking Information

• First Submitted Date: July 27, 2022
• First Posted Date: August 4, 2022
• Last Update Posted Date: February 16, 2023
• Actual Study Start Date: December 21, 2022
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2022)

• Maximum Tolerated Dose (MTD) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: through study completion, an average of 1 year ]
  RP2D will be the MTD

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dual BET and CBP/p300 Inhibitor in Patients With 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Dose escalation/de-escalation will follow rules by employing the Bayesian optimal interval (BOIN) method.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Castrate Resistant Prostate Cancer
• NUT Carcinoma

Intervention

Drug: EP31670

EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.

Other Name: NEO2734

Study Arms

Experimental: Arm 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.

Intervention: Drug: EP31670

• Publications *: Eickhoff N, Bergman AM, Zwart W. Homing in on a Moving Target: Androgen Receptor Cistromic Plasticity in Prostate Cancer. Endocrinology. 2022 Oct 11;163(11):bqac153. doi: 10.1210/endocr/bqac153.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 3, 2022): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Judy Chiao, MD; (561) 865-6098; studies@epigenetix.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05488548
• Other Study ID Numbers: EP31670-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Epigenetix, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Epigenetix, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Judy Chiao, MD; Epigenetix, Inc.

• PRS Account: Epigenetix, Inc.
• Verification Date: February 2023