A Study of PEP08 in Patients With MTAP-Del Advanced or Metastatic Solid Tumors

Official title

A Phase 1a/1b Study Evaluating the Clinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Efficacy of PEP08 as Monotherapy and Combination Therapy in MTAP-Del Advanced or Metastatic Solid Tumors

Overview

This is a first-in-human clinical study of PEP08, a novel cancer therapy being evaluated both as monotherapy and in combination with other treatments in patients with advanced or metastatic solid tumors harboring MTAP deletion. The study will be conducted in three parts, with Part 1 currently open for enrollment. The primary objectives of the study are to: * Evaluate the safety and tolerability of PEP08, PK and PD * Determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) * Assess preliminary signs of anti-tumor activity of PEP08 Key study questions include: * What is the recommended dose of PEP08 for further development? * Wht is the tolerable dose of PEP08 when administered alone or in combination? * Does PEP08 show early evidence of clinical activity in patients with MTAP-deleted tumors? Participants in the study will: * Receive PEP08 alone or in combination with another anti-cancer agent, depending on the study part * Attend regular clinic visits for treatment administration, laboratory assessments, and tumor evaluations * Be enrolled in one of the following study phases over time: * \- Part 1: Monotherapy dose escalation (currently enrolling). * \- Parts 2 and 3 (monotherapy extension and combination therapy) will be activated in future protocol amendments.

Interventions

• Drug PEP08
  PEP08 is an oral, potent, MTA-cooperative PRMT5 inhibitor.

Primary outcome measures

• Number of Participants Experiencing Adverse Events (AE) [Time frame: Up to 2 years]
• Number of Participants Experiencing Serious Adverse Events (SAE) [Time frame: Up to 2 years]
• Number of Patients who Experience Dose-Limiting Toxicity [Time frame: 21 days]

Secondary outcome measures (6)

• Area under the plasma concentration versus time curve (AUC) [Time frame: Up to 6 days]
• Maximum observed plasma concentration (Cmax) [Time frame: Up to 6 days]
• Maximum observed plasma concentration (Cmin) [Time frame: Up to 6 days]
• Time to achieve maximal plasma concentration (Tmax) [Time frame: Up to 6 days]
• Terminal elimination half-life (t1/2) [Time frame: Up to 6 days]
• Objective Response Rate (ORR) per RECIST v1.1 [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• Participants must be adults (≥18 years) and sign informed consent before undergoing any study-related procedures.
• Eligible participants must have advanced or metastatic solid tumors that are not treatable with surgery or radiation, and show evidence of MTAP gene homozygous deletion or MTAP protein loss based on tumor tissue analysis.
• Participants must have previously received standard treatment for their cancer type, and either experienced disease progression, be refractory, or be intolerant to such therapies.
• At least one measurable lesion is required, evaluated by standard imaging criteria (RECIST v1.1).
• Good general physical condition (ECOG performance status 0-1 for dose escalation; broader range allowed for other parts).
• Adequate function in key organs.
• Able to swallow oral medication and comply with study requirements.
• Women of childbearing potential and men with reproductive potential must use effective contraception during and after the study.

Exclusion criteria

• Recent cancer treatment, immunotherapy, or investigational drugs are not allowed before starting the study.
• Live vaccines received shortly before treatment are not allowed.
• Previous use of drugs with similar mechanisms to the study treatment is not allowed.
• Active or unstable brain or meningeal metastases, unless previously treated and stable without needing local treatment or high-dose steroids.
• History of other cancers within the last 2 years, unless low-risk and treated (e.g., in situ or certain skin cancers).
• Uncontrolled disease-related complications (e.g., abnormal calcium levels, fluid buildup around organs).
• Active HIV, hepatitis B or C infections that are not well-controlled.
• Ongoing serious infections or systemic conditions requiring isolation.
• Significant heart disease, such as recent heart failure, ischemia, or arrhythmias.
• History of severe digestive conditions or surgeries affecting drug absorption.
• Recent major surgery.
• Unresolved serious side effects from prior cancer treatment.
• Currently pregnant or breastfeeding.
• Poorly controlled blood pressure or lung conditions.
• Other serious illnesses (e.g., severe anemia, psychiatric or social issues affecting study compliance).
• Any condition that may pose a safety risk or interfere with the study, as judged by the investigator.
• Known drug or substance abuse that may affect study participation.
• Allergy to the study drug or any of its components.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 3 centers

• China Medical University Hospital — Taichung
• National Taiwan University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei

Australia · 1 center

• Westmead Hospital — Wentworthville

Identifiers

NCT: NCT06973863 · PEP08-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗