New treatment for advanced solid tumors and blood cancers

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

This study is testing a new oral treatment for people with advanced solid tumors and blood cancers to see how safe it is and what the highest dose they can take is.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 75 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Epigenetix, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 6 sites (Phoenix, Arizona and 5 other locations)
• Trial ID: NCT05488548 on ClinicalTrials.gov

What this trial studies

This Phase 1, first-in-human study evaluates EP31670, a dual BET and CBP/p300 inhibitor, in patients with advanced solid tumors and hematological malignancies. The study aims to assess the safety and determine the maximum tolerated dose of EP31670 administered orally. It includes patients with castration-resistant prostate cancer, NUT midline carcinoma, chronic myelomonocytic leukemia, and myelofibrosis, who have not responded to standard treatments. The trial is open-label and multi-center, focusing on dose escalation to find the optimal therapeutic level.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced solid tumors or hematological malignancies that have not responded to existing therapies.

Not a fit: Patients with early-stage cancers or those who have not yet undergone standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat cancers.

How similar studies have performed: Other studies have shown promise with similar dual inhibitor approaches, suggesting potential for success in this novel treatment.

Eligibility criteria

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

Where this trial is running

Phoenix, Arizona and 5 other locations

• Mayo Clinic Arizona — Phoenix, Arizona, United States (Recruiting)
• Mayo Clinic Florida — Jacksonville, Florida, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• Mayo Clinic Rochester — Rochester, Minnesota, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• University of Washington/Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Study coordinator: Judy Chiao, MD

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