Clinical trial NCT06973863: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Solid Tumors
MTAP-deleted Solid Tumors
MTAP Deletion
Keywords: MTAP-del
PRMT5 inhibitor
Lead sponsor: PharmaEngine
Sponsor class: INDUSTRY
First posted: 2025-05-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AE)
timeFrame: Up to 2 years
measure: Number of Participants Experiencing Serious Adverse Events (SAE)
timeFrame: Up to 2 years
measure: Number of Patients who Experience Dose-Limiting Toxicity
timeFrame: 21 days
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to 6 days
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to 6 days
measure: Maximum observed plasma concentration (Cmin)
timeFrame: Up to 6 days
measure: Time to achieve maximal plasma concentration (Tmax)
timeFrame: Up to 6 days
measure: Terminal elimination half-life (t1/2)
timeFrame: Up to 6 days
measure: Objective Response Rate (ORR) per RECIST v1.1
timeFrame: Up to 2 years
Other outcomes:
Locations:
Study officials:
References: