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

NCT05488548 | Recruiting Phase 1 FDA Drug

• 1 other identifier: EP31670-01
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 6

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

Conditions

Castrate Resistant Prostate Cancer; NUT Carcinoma; Chronic Myelomonocytic Leukemia; Myelofibrosis

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (3)

Part 1

EXPERIMENTAL

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

Part 2

EXPERIMENTAL

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.

Drug: EP31670

Part 3

EXPERIMENTAL

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

Drug: EP31670

Interventions

EP31670 DRUG

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

Also known as: NEO2734

Part 1; Part 2; Part 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Epigenetix, Inc.: lead

Study Sites (6)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Washington/Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 36125208 DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Primary Myelofibrosis

Interventions

NEO2734

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders

Study Officials

• Judy Chiao, MD

  Epigenetix, Inc.

  STUDY DIRECTOR

Central Study Contacts

Judy Chiao, MD

CONTACT

(561) 865-6098; studies@epigenetix.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: August 4, 2022
• Study Start: December 21, 2022
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: January 14, 2025

Record last verified: 2024-09

Locations

US (6)