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

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

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