Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC), a group of lung cancers that have spread to nearby tissues or to other parts of the body. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are proteins that help cells to grow and divide. A damage (also called mutation) to the building plans (genes) for these proteins in cancer cells leads to a production of abnormal EGFR and/or HER2. These abnormal proteins drive the growth and the spread of the cancer. Several EGFR and/or HER2 mutations exist in the cancer cells. The study treatment, BAY2927088, is expected to block the mutated EGFR and HER2 proteins which may stop the spread of NSCLC. The main purpose of this study is to learn: Escalation, Backfill, and Expansion Part: * How safe is BAY2927088 for the participants? * What is the highest dose of BAY2927088 that can be tolerated (maximum tolerated dose) by or given to (maximum administered dose) the participants? * How does BAY2927088 move into, through, and out of the bodies of the participants? For this, the researchers will measure the followings: * The number of participants with medical problems, also called adverse events and serious adverse events, and their severity * The number of participants who discontinue study treatment due to an adverse event. * The highest dose of BAY2927088 that the participants can take without having adverse events (maximum tolerated dose (MTD)) or the maximum dose that is tested and found to be safe for the participants in case MTD cannot be found out (maximum administered dose (MAD)) of BAY2927088 * Number of participants experiencing adverse events that prevent an increase in the dose of BAY2927088 (dose-limiting toxicities (DLTs)) at each dose level * The (average) total level of BAY2927088 in the blood (also called AUC) after receiving single or multiple doses of BAY2927088 * The (average) highest level of BAY2927088 in the blood (also called Cmax) after receiving a single or multiple doses of BAY2927088 Extension Part * How well does BAY2927088 work in participants? For this, the researchers will measure the following: • Percentage of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)). This will be assessed by doctors other than the study doctor. This study has 4 parts: * The escalation part aims to find the maximum daily amount (dose) of BAY2927088 that participants can receive. * The backfill part aims to test the doses of BAY2927088 that are considered safe in the escalation part by giving it to more participants. This will help find optimal doses of BAY2927088 that work well and are safe to be tested in the next part. * The expansion part aims to determine the dose of BAY2927088 to be tested in further studies. * The extension part aims to determine whether the selected dose of BAY2927088 from the expansion part works well. The participants in this study will take the study treatment BAY2927088 in 3-week periods called "cycles". They will in general take BAY2927088 once or twice daily as a liquid/tablet by mouth until their cancer gets worse, they have medical problems, they leave the study, or the study is terminated. Participants will have no more than 5 visits per cycle. During the study, the study team will: * take blood and urine samples, * check the status of the cancer by doing computed tomography (CT) or magnetic resonance imaging (MRI) scans, * check the participants' overall health and heart health, * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is considered "serious" when it leads to death, puts the participant's life at risk, requires hospitalization, causes disability, causes a baby being born with medical problems, or is medically important.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
370
Oral administration
Oral administration
Oral administration
Banner MD Anderson Cancer Center at Banner Gateway Medical Center
Gilbert, Arizona, United States
City of Hope - Duarte Cancer Center
Duarte, California, United States
Emory Winship Cancer Institute
Atlanta, Georgia, United States
The Center for Cancer and Blood Disorders
Bethesda, Maryland, United States
Dana-Farber Cancer Institute - Oncology Department
Boston, Massachusetts, United States
Number of participants with treatment-emergent adverse events (TEAEs)
Time frame: Up to 30 days after the last administration of study treatment
Number of participants with treatment-emergent serious adverse events (TESAEs)
Time frame: Up to 30 days after the last administration of study treatment
Severity of TEAEs
Time frame: Up to 30 days after the last administration of study treatment
Severity of TESAEs
Time frame: Up to 30 days after the last administration of study treatment
Number of participants who discontinue study treatment due to an AE
Time frame: About 4 years (Up to the end of study treatment)
Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2927088 within the DLT observation period in Dose Escalation (including participants from Backfill qualifying for the MTD population)
Time frame: At the end of Cycle 1 of a 21-day cycle
Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY2927088 in the DLT observation period in Dose Escalation (including participants from Backfill)
In Dose Escalation (including participants from Backfill)
Time frame: At the end of Cycle 1 of a 21-day cycle
Cmax of BAY2927088
Cmax: Maximum/peak concentration
Time frame: Cycle 1, Day 1 (Cycle duration is 21 days)
AUC(0-24) of BAY2927088 for QD
AUC: Area under the concentration vs. time curve. AUC(0-24): AUC from time 0 to 24 hours post dose. QD: Quaque die (once daily)
Time frame: Cycle 1, Day 1 (Cycle duration is 21 days)
AUC(0-12) of BAY2927088 for BID
If applicable. AUC(0-12): AUC from time 0 to 12 hours post dose. BID: Bis in die, 2 times daily.
Time frame: Cycle 1, Day 1 (Cycle duration is 21 days)
Cmax,md of BAY2927088
Cmax,md: Cmax after multiple dose administrations
Time frame: Cycle 1, Day 15 (Cycle duration is 21 days)
AUC(0-24)md of BAY2927088 for QD
AUC(0-24)md: AUC(0-24) after multiple dose administrations
Time frame: Cycle 1, Day 15 (Cycle duration is 21 days)
AUC(0-12)md of BAY2927088 for BID
If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations
Time frame: Cycle 1, Day 15 (Cycle duration is 21 days)
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR) in extension part
Time frame: From the start of the study treatment up to 12 months
Overall response rate (ORR) as per RECIST v1.1 by investigator assessment
RECIST v1.1: Response Evaluation Criteria in Solid Tumors, version 1.1
Time frame: About 4 years
Recommended phase 2 dose (RP2D) of BAY2927088
Time frame: About 1.5 years
ORR per RECIST v1.1 by Investigator assessment in extension part
Time frame: From the start of the study treatment up to 12 months
Disease control rate (DCR) per RECIST v1.1 by Investigator assessment and BICR in extension part
Time frame: From the start of the study treatment up to 12 months
Duration of response (DOR) per RECIST 1.1 by Investigator assessment and BICR in extension part
Time frame: From the start of the study treatment up to 12 months
Progression-free survival (PFS) per RECIST 1.1 by Investigator assessment and BICR in extension part
Time frame: From the start of the study treatment up to 12 months
Overall survival (OS) in extension part
Time frame: From the start of the study treatment up to 12 months
Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) categorized by severity in extension part
Time frame: Up to 30 days after the last administration of study treatment
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