A Study of PRMT5 Inhibitor BAY 3713372 in Participants With MTAP-deleted Solid Tumors

Официальное название

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.

Обзор

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 learn how safe BAY 3713372 is, how the body processes it, and how well it works in people with MTAP-deleted solid tumors. For this, the researchers will study and analyze: * the number of participants who have adverse events (AEs) after receiving different doses of BAY 3713372 and the AE's severity. * the number of participants who experience dose-limiting toxicities (DLTs) after receiving different doses of BAY 3713372, the DLT's 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 take part in one of the eight distinct groups or "intervention cohorts" of the study. The study will start with a dose escalation phase where distinct groups of participants will receive different doses of BAY 3713372 alone to find the dose that is deemed safe and works best for the participants. When this dose has been found, a larger number of participants will receive BAY 3713372 alone or with other treatments in a dose expansion phase. 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.

Вмешательства

• Препарат BAY 3713372
  Daily oral administration

Первичные конечные точки

• Dose Escalation (Master and Intervention Cohort 1): Number of participants with treatment-emergent adverse events (TEAEs) [Срок оценки: From the first administration of study intervention up to 30 days after the last dose of study intervention]
• Dose Escalation (Master and Intervention Cohort 1): Number of participants with treatment-emergent serious adverse events (TESAEs) [Срок оценки: From the first administration of study intervention up to 30 days after the last dose of study intervention]
• Dose Escalation (Master and Intervention Cohort 1): Severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) [Срок оценки: From the first administration of study intervention up to 30 days after the last dose of study intervention]
• Dose Escalation (Master and Intervention Cohort 1): Incidence of dose-limiting toxicities (DLTs) [Срок оценки: From the first dose of study intervention to the end of Cycle 1 (each cycle is 21 days)]
• Dose Escalation (Master and Intervention Cohort 1): Number of participants with DLTs [Срок оценки: From the first dose of study intervention to the end of Cycle 1 (each cycle is 21 days)]
• Dose Escalation (Master and Intervention Cohort 1): Maximum concentration (Cmax) of the respective dosing interval of BAY 3713372 [Срок оценки: From the first dose of study intervention up to Cycle 2 Day 1 (each cycle is 21 days)]
• Dose Escalation (Master and Intervention Cohort 1): Area under the curve (AUC) of the respective dosing interval of BAY 3713372 [Срок оценки: From the first dose of study intervention up to Cycle 2 Day 1 (each cycle is 21 days)]
• Dose Expansion (Master, Intervention Cohorts 1 - 6): Objective response rate (ORR) [Срок оценки: Approximately 1.5 years]
• Dose Expansion (Intervention Cohorts 3, 4 and 6): Number of participants with DLTs [Срок оценки: From the first dose of study intervention to the end of Cycle 1 (each cycle is 21 days, except for Intervention Cohort 6, which has a cycle length of 28 days)]
• Intervention Cohort 7: Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) [Срок оценки: From the first administration of study intervention up to 30 days after the last dose of study intervention]

Вторичные конечные точки (12)

• Dose Escalation (Master and Intervention Cohort 1): Objective response rate (ORR) [Срок оценки: Approximately 1.5 years]
• Dose Escalation (Master and Intervention Cohort 1): Duration of response (DOR) [Срок оценки: Approximately 3 years]
• Dose Escalation (Master and Intervention Cohort 1): Progression-free survival (PFS) [Срок оценки: Approximately 3 years]
• Dose Escalation (Master and Intervention Cohort 1): Time to response (TTR) [Срок оценки: Approximately 1.5 years]
• Dose Expansion (Master, Intervention Cohorts 1 - 6): Number of participants with treatment-emergent adverse events (TEAEs) [Срок оценки: From the first administration of study intervention up to 30 days after the last dose of study intervention]
• Dose Expansion (Master, Intervention Cohorts 1 - 6): Number of participants with treatment-emergent serious adverse events (TESAEs) [Срок оценки: From the first administration of study intervention up to 30 days after the last dose of study intervention]
• Dose Expansion (Master, Intervention Cohorts 1 - 6): Severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) [Срок оценки: From the first administration of study intervention up to 30 days after the last dose of study intervention]
• Dose Expansion (Master, Intervention Cohorts 1, 3, 4, and 6): Incidence of dose-limiting toxicities (DLTs) [Срок оценки: From the first dose of study intervention to the end of Cycle 1 (each cycle is 21 days, except for Intervention Cohort 6, which has a cycle length of 28 days)]
• Dose Expansion (Master, Intervention Cohorts 1 - 6): Duration of response (DOR) [Срок оценки: Approximately 3 years]
• Dose Expansion (Master, Intervention Cohorts 1 - 6): Progression-free survival (PFS) [Срок оценки: Approximately 3 years]
• Dose Expansion (Master, Intervention Cohorts 1 - 6): Time to response (TTR) [Срок оценки: Approximately 1.5 years]
• Dose Expansion (Master, Intervention Cohorts 1 - 4, and 6): Maximum concentration (Cmax) of the respective dosing interval of BAY 3713372 [Срок оценки: From the first dose of study intervention up to Cycle 2 Day 1 (each cycle is 21 days, except for Intervention Cohort 6, which has a cycle length of 28 days)]

Критерии участия

Критерии включения

• Participant must be ≥ 18 years old of age, or the legal age of consent in the jurisdiction of the country in which the study takes place, at the time of signing the informed consent.
• At least one measurable lesion that would qualify as target lesion by 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.

Критерии исключения

• Previous additional cancer other 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.
• 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 based on the investigator's clinical assessment and discretion.
• 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 within 4 weeks before start of study intervention.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 17 центров

• UAB O'Neal Comprehensive Cancer Center - The Kirklin Clinic of UAB Hospital — Birmingham
• City of Hope - Duarte Cancer Center — Duarte
• UCLA Health Bowyer Oncology Center — Los Angeles
• UCSF Helen Diller Medical Center at Parnassus Heights - Neurology — San Francisco
• Stanford University Medical Center - Neurology — Stanford
• UCHealth Cancer Center - Anschutz Medical Campus - University of Colorado Cancer Center — Aurora
• Sarah Cannon Research Institute at HCA HealthONE Presbyterian St. Luke's — Denver
• Sarah Cannon Research Institute at Florida Cancer Specialists- Lake Nona — Orlando
• … и ещё 9 центров

Испания · 8 центров

• Hospital San Pedro | Oncologia — Logroño
• Clinica Universidad De Navarra | Pamplona | Oncologia — Pamplona
• NEXT - Hospital Universitario Quironsalud Madrid | Oncologia — Pozuelo de Alarcón
• Hospital Hm Nou Delfos | Oncologia — Barcelona
• Hospital Universitari Vall D Hebron | Oncologia — Barcelona
• Hospital Universitario Fundacion Jimenez Diaz | Oncologia — Madrid
• Hospital Universitario Virgen De La Victoria | Oncologia — Málaga
• Hospital Clinico Universitario De Valencia | Oncologia — Valencia

Япония · 6 центров

• Nagoya University Hospital — Nagoya
• National Cancer Center Hospital East — Kashiwa
• Kindai University Hospital — Sakai
• Shizuoka Cancer Center — Sunto
• National Cancer Center Hospital — Chuo-ku
• The Cancer Institute Hospital of JFCR — Koto-ku

Италия · 5 центров

• Centro di Riferimento Oncologico di Aviano - Oncologia Medica e dei Tumori Immuno-Correlat — Aviano
• Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Oncologia Medica 1 — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Fase I — Roma
• I.F.O. Istituti Fisioterapici Ospitalieri - Sperimentazioni cliniche Fase 1 e Medicina di — Roma
• Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia — Rozzano

Австралия · 4 центра

• Chris O'Brien Lifehouse — Camperdown
• Concord Repatriation General Hospital (CRGH) (Concord Hospital) - Concord Cancer Centre — Concord
• Northern Hospital — Epping
• Calvary Mater Hospital Newcastle - Oncology — Waratah

Бельгия · 4 центра

• Antwerp University Hospital | Oncology Department — Antwerp
• Ghent University Hospital | Drug Research Unit Department — Ghent
• UZ Leuven Gasthuisberg - Pneumology Department — Leuven
• Centre Hospitalier Universitaire (CHU) de Liege - Domaine Universitaire du Sart Tilman - M — Liège

Нидерланды · 3 центра

• Nederlands Kanker Instituut — Amsterdam
• Erasmus Medisch Centrum — Rotterdam
• Universitair Medisch Centrum Groningen (UMCG) - UMC Groningen Comprehensive Cancer Center — Groningen

Сингапур · 3 центра

• National University Hospital Medical Centre — Singapore
• National Cancer Center Singapore - Oncology Department — Singapore
• Icon Cancer Centre — Singapore

Китай · 2 центра

• Beijing Cancer Hospital - Oncology Department — Пекин
• Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech. — Ухань

Чехия · 2 центра

• Fakultní nemocnice Olomouc - Onkologická klinika — Olomouc
• Masarykova Univerzita - Masarykuv Onkologicky Ustav (MOU) - Klinika Komplexni Onkologicke — Brno

Дания · 2 центра

• Rigshospitalet Copenhagen University Hospital | Oncology Department — Copenhagen
• Odense University Hospital | Svendborg Sygehus - Oncology Department — Odense

Швеция · 2 центра

• Karolinska Universitetssjukhuset - Solna - Fas I-enheten Solna CKC — Stockholm
• Sahlgrenska Universitetssjukhuset - Sahlgrenska Sjukhuset - Klinisk prövningsenhet Fas I/F — Gothenburg

Великобритания · 2 центра

• The Royal Marsden NHS Foundation Trust | Sutton - Oak Foundation Drug Development Unit — Sutton
• The Christie NHS Foundation Trust | Christie Hospital - Experimental Cancer Medicine Team — Manchester

Идентификаторы

NCT: NCT06914128 · 22931 · 2025-520623-24-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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