Clinical trial NCT05488548: Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies
Official title: A Phase 1 Study of EP31670, a Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Castrate Resistant Prostate Cancer
NUT Carcinoma
Chronic Myelomonocytic Leukemia
Myelofibrosis
Lead sponsor: Epigenetix, Inc.
Sponsor class: INDUSTRY
First posted: 2022-08-04
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Dose escalation/de-escalation will follow rules by employing the Bayesian optimal interval (BOIN) method for Part 1 and Part 2 and traditional 3+ 3 by modified Fibonacci sequence for Part 3
Primary purpose: TREATMENT

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 and Hematological Malignancies

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 as well as chronic myelomonocytic leukemia (CMML), myelofibrosis (MF) and other targeted hematological malignancies.

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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Within 3 weeks (one cycle) of treatment
measure: Dose Limiting Toxicities (DLT)
timeFrame: Within 3 weeks (one cycle) of treatment
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington/Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Epigenetix, Inc.
name: Judy Chiao, MD
role: STUDY_DIRECTOR
References:
citation: Eickhoff N, Bergman AM, Zwart W. Homing in on a Moving Target: Androgen Receptor Cistromic Plasticity in Prostate Cancer. Endocrinology. 2022 Oct 11;163(11):bqac153. doi: 10.1210/endocr/bqac153.