First in Human Study of BAY2927088 in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations in the Genes of Epidermal Growth Factor Receptor (EGFR) and/or Human Epidermal Growth Factor Receptor 2 (HER2)
18 Years and older, Male and Female
21607 (primary)
NCI-2021-12361
2021-003022-77
Summary
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 BAY 2927088
- The (average) highest level of BAY 2927088 in the blood (also called Cmax) after
receiving a single or multiple doses of BAY2927088 Extension Part
- How well does BAY 2927088 work in participants?
For this, the researchers will measure the following:
â?¢ 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 BAY 2927088 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.
Eligibility
- Documented histologically or cytologically confirmed locally advanced NSCLC, not suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small cell or mixed histologies are excluded).
- Documented disease progression after treatment with at least one prior systemic therapy for advanced disease. Participants who do not have standard of care access due to any reason, are intolerant to, or are not eligible for standard treatments, may also be eligible. Note: Except for participants eligible for one of the groups (Expansion or Extension) who
should have received no prior systemic treatment for locally advanced or metastatic
disease.
- Adequate archival tumor tissue (ideally taken after last targeted treatment and not older than 6 months) has to be available, either from primary or metastatic sites. If archival material is not available, a fresh tumor biopsy should be performed if feasible and if the procedure poses no significant risk for the participant.
- Measurable disease by RECIST v1.1 with at least one lesion not chosen for biopsy during the screening period (if a biopsy is taken during screening) that can be accurately measured at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements. A biopsied lesion should not be used as a target lesion for RECIST 1.1 tumor assessments. Previously irradiated lesions must have shown progression to be considered measurable.
- Documented activating EGFR and/or HER2 mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (United States [US] sites) or an equally accredited (outside of the US) local laboratory
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Minimum life expectancy of 12 weeks.
- Adequate bone marrow function as assessed by the following laboratory tests to be conducted within 7 days before the first dose of study treatment:
- Hemoglobin â?¥ 9.0 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within 2 weeks prior to testing.
- Platelets â?¥ 100 Ã? 10^9 cells/L.
- Absolute neutrophil count â?¥ 1.5 Ã?10^9 cells/L. Criteria must be met without the use of hematopoietic growth factors (e.g., G-CSF) within 2 weeks prior to testing.
- Adequate kidney function as assessed by following laboratory test to be conducted within 7 days before the first dose of study treatment: a. Estimated glomerular filtration rate (eGFR) > 50 mL/min per 1.73 m^2 according to the Modification of Diet in renal Disease Study Group (MDRD) formula.
- Adequate liver function as assessed by following laboratory tests to be conducted within 7 days before the first dose of study treatment:
- Total bilirubin â?¤ 1.5 Ã? ULN (or â?¤ 3 X ULN for participants with documented Gilbert-Meulengracht Syndrome, or for participants with hyperbilirubinemia considered due to liver metastasis).
- Aspartate transaminase and alanine transaminase â?¤ 2.5 Ã? ULN (or â?¤ 5 Ã? ULN if due to liver involvement by tumor).
Treatment Sites in Georgia
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