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

Condition(s) studied

Investigational drug(s) / intervention(s)

BAY 3713372: Daily oral administration

Study 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 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.

Eligibility

Primary outcome measure(s)

• Dose Escalation (Master and Intervention Cohort 1): Number of participants with treatment-emergent adverse events (TEAEs) — From the first administration of study intervention up to 30 days after the last dose of study intervention
  TEAEs will be graded according to NCI-CTCAE v.5.0 and will be reported using the latest version of MedDRA coding dictionary
• Dose Escalation (Master and Intervention Cohort 1): Number of participants with treatment-emergent serious adverse events (TESAEs) — From the first administration of study intervention up to 30 days after the last dose of study intervention
  TESAEs will be graded according to NCI-CTCAE v.5.0 and will be reported using the latest version of MedDRA coding dictionary
• Dose Escalation (Master and Intervention Cohort 1): Severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) — From the first administration of study intervention up to 30 days after the last dose of study intervention
  TEAEs and TESAEs will be graded according to NCI-CTCAE v.5.0 and will be reported using the latest version of MedDRA coding dictionary
• Dose Escalation (Master and Intervention Cohort 1): Incidence of dose-limiting toxicities (DLTs) — From the first dose of study intervention to the end of Cycle 1 (each cycle is 21 days)
  DLTs per participants. DLTs will be graded according to NCI-CTCAE v.5.0
• Dose Escalation (Master and Intervention Cohort 1): Number of participants with DLTs — From the first dose of study intervention to the end of Cycle 1 (each cycle is 21 days)
  Number of participants with at least one DLT
• Dose Escalation (Master and Intervention Cohort 1): Maximum concentration (Cmax) of the respective dosing interval of BAY 3713372 — 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 — 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) — Approximately 1.5 years
  Determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Dose Expansion (Intervention Cohorts 3, 4 and 6): Number of participants with DLTs — 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)
  Number of participants with at least one DLT
• Intervention Cohort 7: Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) — From the first administration of study intervention up to 30 days after the last dose of study intervention
  TEAEs will be graded according to NCI-CTCAE v.5.0 and will be reported using the latest version of MedDRA coding dictionary
• Intervention Cohort 7: Severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) — From the first administration of study intervention up to 30 days after the last dose of study intervention
  TEAEs will be graded according to NCI-CTCAE v.5.0 and will be reported using the latest version of MedDRA coding dictionary
• Intervention Cohort 7: Number of participants with DLTs — From the first dose of study intervention to the end of Cycle 1 (each cycle is 21 days)
  Number of participants with at least one DLT
• Intervention Cohort 7: Brain and brain tumor PK concentration of BAY 3713372 — From first dose through day of surgery (approximately 7 ± 2 days)
  Concentration of BAY 3713372 in enhancing and non-enhancing brain tumor tissue obtained at definitive surgery, with corresponding time-matched plasma concentrations and estimation of tumor-to-plasma exposure ratios
• Intervention Cohort 7: Tumor tissue SDMA levels — From first dose through day of surgery (approximately 7 ± 2 days)
  Change in symmetric dimethylarginine (SDMA) levels in brain tumor tissue collected at definitive surgery following neoadjuvant BAY 3713372 treatment, as a pharmacodynamic marker of PRMT5 inhibition

Trial sites (63)

+ 23 more sites — see the full list on the official registry below.

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