EP102 Safety and Efficacy in METTL3 Modulation in Advanced Solid Tumors

Official title

A Phase 1 Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered EP102 Monotherapy in Participants With Advanced Solid Tumors

Overview

This the first-in-human (FIH) study for the Investigational Medicinal Product (IMP) EP102, is designed to explore the maximum tolerated dose (MTD), the overall safety profile, its pharmacokinetic (PK) / pharmacodynamic (PD) profile, and an exploratory evaluation of antitumor activity in participants with advanced solid tumors, who have no available standard therapy or who have failed standard therapies. This study will inform on recommended doses for further studies, e.g. dose optimization studies and / or efficacy and safety studies.

Interventions

• Drug EP102
  EP102 will be administered orally

Primary outcome measures

• To assess the safety and tolerability of EP102 monotherapy [Time frame: Up to 21 Days after first administration]
• To assess the safety and tolerability of EP102 monotherapy [Time frame: Up to 21 Days after first administration]
• Explore the maximum tolerated dose (MTD) and recommended doses of EP102 monotherapy for subsequent studie [Time frame: Up to 21 Days after first administration]

Secondary outcome measures (6)

• To characterize the pharmacokinetic (PK) profile of EP102 [Time frame: Up to 21 days after first administration]
• To characterize the pharmacokinetic (PK) profile of EP102 [Time frame: Up to 21 Days after first administration]
• To characterize the pharmacokinetic (PK) profile of EP102 [Time frame: Up to 21 Days after first administration]
• To characterize the pharmacokinetic (PK) profile of EP102 [Time frame: Up to 21 Days after first administration]
• To characterize the pharmacokinetic (PK) profile of EP102 [Time frame: Up to 21 Days after first administration]
• To preliminarily evaluate the anti-tumor activity pharmacodynamic (PD) of EP102 monotherapy [Time frame: Up to 21 days after administration and up until study end]

Eligibility criteria

Inclusion criteria

• Participants must have a histological diagnosis of locally advanced or metastatic malignant solid tumors of one of the following cancer types:

• ovarian cancer
• cervical cancer
• endometrial cancer
• testicular cancer
• cholangiocarcinoma
• thyroid cancer
• parathyroid cancer
• adrenal cancer
• pancreatic cancer
• non-small-cell lung cancer (NSCLC)
• head-and neck cancer
• renal cell cancer
• urethral cancer
• bladder cancer
• colorectal cancer
• gastric cancer
• esophageal cancer
• triple-negative breast cancer
• thymoma
• soft tissue sarcoma
• Participants must have failed (i.e. progressed on, or been intolerant to standard treatment), or no standard treatment must exist, or they must have refused standard treatment. All participants must have received at least one prior line of systemic therapy.
• Participants must have at least one measurable lesion per RECIST v1.1.
• Participant must have a life expectancy of at least 12 weeks.

Exclusion criteria

• Participants with an active severe infection or unexplained fever > 38.5°C during screening or on the first day of study drug administration are excluded. However, at the Investigator's discretion, participants with tumor-related fever may be enrolled.
• Participants with known human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection (hepatitis B surface antigen (HBsAg) positive in serum), or active hepatitis C virus (HCV) infection (HCV RNA positive in serum).
• Participants with known dysphagia, short-bowel syndrome, gastroparesis, or any condition that may impair the ingestion or gastrointestinal absorption of orally administered drugs.
• Pregnant or breastfeeding participants.
• Participants who have received IMP or devices in other clinical trials within four weeks before the first dose.
• Participants with prior exposure to selective METTL3 inhibitor therapy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Belgium · 4 centers

• Institut Jules Bordet — Brussels
• Cliniques universitaires Saint-Luc — Brussels
• Universitair Ziekenhuis Gent (UZ Gent) - Drug Research Unit Gent (DRUG) — Ghent
• Leuven Cancer Institute (LKI) — Leuven

Spain · 3 centers

• Hospital Universitari Vall d'Hebron - Vall d'Hebron Institute of Oncology — Barcelona
• START Madrid - CIOCC — Madrid
• Hospital Universitario de Santiago de Compostela — Santiago de Compostela

Czechia · 2 centers

• Masaryk Memorial Cancer Institute — Brno
• Olomouc University Hospital — Olomouc

Netherlands · 2 centers

• Netherlands Cancer Institute (NKI) — Amsterdam
• University Medical Center Groningen, University of Groningen Department of Medical Oncolog — Groningen

Publications

• Dutheuil G, Oukoloff K, Korac J, Lenoir F, El Bousmaqui M, Probst N, Lapin A, Nakhabina G, Sorlet C, Parmentier N, Karila D, Ghavtadze N, Casault P, Claridge S, Sapmaz S, Slater MJ, Fraser GL. Discovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models. J Med Chem. 2025 Feb 13;68(3):2981-3003. doi: 10.1021/acs.jmedchem.4c02225. PMID 39883878
• Abbad L, Chatziantoniou C. Discovering New Therapies for Kidney Fibrosis: The Promise of Epigenetic and Epitranscriptomic Modulation. J Am Soc Nephrol. 2026 Jul 1;37(7):1367-1369. doi: 10.1681/ASN.0000001136. Epub 2026 May 28. No abstract available. PMID 42210870

Identifiers

NCT: NCT07163325 · EP102-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗