Clinical trial NCT06914128: A First-in-human Study to Learn How Safe BAY 3713372 is and How it Works in Participants With MTAP-deleted Solid Tumors
Official title: A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of BAY 3713372, a Novel 2nd Generation PRMT5 Inhibitor, in Participants With MTAP-deleted Solid Tumors.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: MTAP-deleted Solid Tumors
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2025-04-06
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study treatment, BAY 3713372, is under development to treat MTAP (methylthioadenosine phosphorylase)-deleted solid tumors. It is thought to work by blocking the protein arginine N-methyltransferase 5 (PRMT5). This may kill the MTAP-deleted cancer cells while sparing the normal cells.

The main objective of this first-in-human study is to check if BAY 3713372 is safe for further testing and find the dose that could be used to treat different cancer types that are also MTAP-deleted in future studies.

For this, the researchers will study and analyze:

* the number of participants who have adverse events after receiving different doses of BAY 3713372 and their severity.
* the number of participants who experience dose-limiting toxicities (DLTs) after receiving different doses of BAY 3713372, their severity and how often they happened. A DLT is a pre-defined medical problem caused by a specific dose of a drug that is too severe to continue using that dose.
* the total amount of BAY 3713372 in participants' blood (also called AUC) over time after single and multiple doses.
* the highest level of BAY 3713372 in participants' blood (also called Cmax) after single and multiple doses.

Other than the main objective, researchers will also check for the number of participants who show a response to treatment and how long they live without the cancer getting worse.

The study participants will receive BAY 3713372 (starting from low to high doses) in the study, to find the highest safe dose for further testing.

Participants may take the study treatment as long as they benefit from the treatment without any severe medical problems.

Participants will visit the study site:

* at least twice before the treatment starts
* multiple times when they start taking the treatment
* once after 30 days of receiving the last dose and every 9 weeks after that until the cancer worsens, or the participant stops for any other reason

During the study, the doctors and their study team will:

* check participants' health by performing tests such as blood and urine tests, and checking heart health using an electrocardiogram
* check if the participants' cancer has grown and/or spread using computed tomography (CT) or magnetic resonance imaging (MRI) and, if needed, bone scan
* take tumor samples

The study doctors and their team will contact the participants every 3 months until 2 years after the last participant's last dose or the end of the study to learn about the participant's health.


Eligibility criteria: Inclusion Criteria:

* Participant age ≥ 18 years old with solid tumor and at least 1 evaluable lesion as per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
* Homozygous MTAP-deletion identified through molecular testing from a locally certified laboratory.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Participants must have exhausted available standard of care treatments known to be beneficial for this tumor type or for whom these treatments are not acceptable and for whom this trial is a reasonable option

Exclusion Criteria:

* Previous additional cancer else than the one evaluated in this study within the past 2 years except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, localized prostate cancer or other tumors that in the opinion of the investigator, are considered cured or not immediately life-threatening, and will not interfere with the scientific goals of this study.
* Presence of central nervous system (CNS) tumors including progressing, novel and/or symptomatic metastatic brain disease.
* Presence of glioblastoma multiforme (GBM).
* A marked prolongation of QT/QTc interval at screening (e.g., repeated demonstration of a QTc interval \>450 ms). Participants with permanent pacemakers (i.e., a paced rhythm) may be eligible after discussion with the sponsor.
* Cardiac history comprising:

  * History of congestive heart failure Class \>II according to the New York Heart Association Functional Classification.
  * Myocardial infarction less than 6 months before the start of study intervention.
  * Serious cardiac arrhythmias requiring treatment or any clinically important abnormalities in rhythm, conduction or morphology on resting ECG with the exception of atrial fibrillation which is well-controlled and requires only digoxin or beta blockers.
* Unstable angina or new-on major surgery, open biopsy, or significant trauma within 4 weeks before start of study intervention.

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: From the first administration of study intervention up to 30 days after the last dose of study intervention
measure: Number of participants with treatment-emergent serious adverse events (TESAEs)
timeFrame: From the first administration of study intervention up to 30 days after the last dose of study intervention
measure: Severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
timeFrame: From the first administration of study intervention up to 30 days after the last dose of study intervention
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: From first dose of study intervention to the end of Cycle 1 (each cycle is 21 days)
measure: Number of participants with DLTs
timeFrame: From first dose of study intervention to the end of Cycle 1 (each cycle is 21 days)
measure: Maximum concentration (Cmax) of the respective dosing interval of BAY 3713372
timeFrame: From the first dose of study intervention up to Cycle 2 Day 1 (each cycle is 21 days)
measure: Area under the curve (AUC) of the respective dosing interval of BAY 3713372
timeFrame: From the first dose of study intervention up to Cycle 2 Day 1 (each cycle is 21 days)
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Approximately 1.5 years
measure: Duration of response (DOR)
timeFrame: Approximately 3 years
measure: Progression-free survival (PFS)
timeFrame: Approximately 3 years
measure: Time to response (TTR)
timeFrame: Approximately 1.5 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists- Lake Nona
state: Florida
city: Grand Rapids
country: United States
facility: START | Midwest
state: Michigan
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: San Antonio
country: United States
facility: START | San Antonio
state: Texas
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital (CRGH) (Concord Hospital) - Concord Cancer Centre
state: New South Wales
city: Singapore
country: Singapore
facility: National University Hospital Medical Centre
city: Singapore
country: Singapore
facility: National Cancer Center Singapore
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust | Sutton - Oak Foundation Drug Development Unit
state: Greater London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust | Christie Hospital - Experimental Cancer Medicine Team
Study officials:
References: