Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: EP31670
EP31670 (also known as NEO2734) is a first-in-class dual BET and CBP/p300 inhibitor.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) [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) [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) [through study completion, an average of 1 year]
RP2D will be the MTD
Eligibility Criteria
Criteria
Inclusion Criteria:
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Relapse or refractory castration-resistant prostate cancer (CRPC) following at least one anti-androgen regimen and a docetaxel-containing regimen OR
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metastatic or unresectable NUT midline carcinoma for which standard curative or palliative measures do not exist; OR
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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
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Eastern Cooperative Oncology Group (ECOG) performance status 0-1
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Life expectancy ≥ 3 months
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Evaluable disease
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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
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Adequate liver function
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Total bilirubin ≤ 1.5 x ULN except in patients diagnosed with Gilbert's disease for which direct bilirubin must be ≤ 1.5 x ULN
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Alanine aminotransferase (ALT) or aspartate Aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN in patients with liver metastases
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Internal normalized ratio for prothrombin time (INR) ≤ 1.2 in patients not receiving chronic anticoagulation
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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.
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Four weeks from major surgery.
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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.
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Ability to understand and willingness to sign the informed consent form.
Exclusion Criteria:
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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
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Corrected QT interval ≥470 msec
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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
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Pregnant or lactating women
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Known history of hepatitis B, hepatitis C requiring antiviral treatment
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Epigenetix, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EP31670-01