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

Launched by EPIGENETIX, INC. · Aug 3, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called EP31670, which is designed to help patients with certain advanced cancers, including castrate-resistant prostate cancer, NUT carcinoma, chronic myelomonocytic leukemia (CMML), and myelofibrosis. The goal is to see if this treatment can effectively target and inhibit specific proteins (BET and CBP/p300) that may contribute to cancer growth. This is the first time the treatment is being tested in humans, and the trial is currently looking for participants.

To be eligible for the trial, patients should be between the ages of 65 and 74 and have specific types of cancers that have not responded to previous treatments. This includes certain advanced cases that have either relapsed or are difficult to treat with standard therapies. Participants will undergo regular assessments to monitor their health and response to the treatment. It's important to note that patients must be able to understand the study and agree to participate by signing an informed consent form. Overall, this trial aims to explore a new approach that could potentially offer hope for patients facing challenging cancer diagnoses.

Gender

ALL

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