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

A Phase 1, first-in-human study of EP31670, a dual BET and CBP/p300 inhibitor in patients
with targeted advanced solid tumors.

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