Lung Cancer Clinical Trial
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)
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. Two mutations observed in NSCLC are called EGFR- or HER2exon20ins and EGFR C797X. The study treatment, BAY2927088, works by blocking the mutated EGFR protein and also its ex20ins version which are present in NSCLC. It is also believed to work against HER2 and HER2ex20ins mutations. Researchers think this may help stop the further spread of NSCLC cancer.
This is the first time that researchers will study BAY2927088 in humans. In this study, the researchers want to learn more about using BAY2927088 in participants who have NSCLC with EGFR and/or HER2 mutations including EGFRex20ins and/or HER2ex20ins mutations.
The main aims of this study are to find for BAY2927088
how safe BAY2927088 is
how it affects the body (also referred to as tolerability)
how BAY2927088 moves into, through and out of the body
the maximum amount of BAY2927088 that the participants can take without too many side effects.
The researchers will also study the action of BAY2927088 against the cancer. This study will have three parts. The first part will help find the most appropriate dose that can be given in the third part.
Each participant of the first, so called dose escalation part, will be assigned to one specific dose group for BAY2927088. The amount of BAY2927088 that is given increases stepwise from one group to the next.
The participants of the second, so called Backfill part will be assigned any specific dose that has already been tested during Part 1 and found to be safe.
The participants of the third, so called dose expansion part, will receive the most appropriate dose of BAY2927088 found in the first and second parts.
During the study, the participants will take the study treatment in 3 week periods called "cycles". They will in general take BAY2927088 once daily until their cancer gets worse, until they have medical problems, until they leave the study or until the study is terminated. Participants will have around 5 visits in each cycle.
During the study, the study team will:
take blood and urine samples
take regular CT or MRI scans to check if the participants' cancer has gotten better or worse
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 any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.
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.
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 ≥ 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 ≥ 100 × 10^9 cells/L.
Absolute neutrophil count ≥ 1.5 ×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) > 60 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 ≤ 1.5 × ULN (or ≤ 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 ≤ 2.5 × ULN (or ≤ 5 × ULN if due to liver involvement by tumor).
Treatment with an EGFR tyrosine kinase inhibitor (TKI) ≤ 8 days or 5x the terminal phase, elimination half-lives, whichever is shorter, prior to the first dose of study drug.
Treatment with a systemic anti-cancer treatment (excluding EGFR TKIs as described above) ≤ 14 days prior to the first dose of study drug.
Radiation therapy, stereotactic radiosurgery (SRS) and palliative radiation ≤ 14 days prior to the first dose of study drug.
Treatment with immunotherapy ≤ 28 days prior to the first dose of study drug.
Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Participants with chronic, but stable Grade 2 toxicities may be allowed to enroll after agreement between the Investigator and Sponsor.
Any history of primary brain or meningeal tumors, presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local treatment (such as radiotherapy or surgery).
History of spinal cord compression or brain metastases with the following exceptions:
Participants with treated brain metastases that are asymptomatic at screening and who are off or receiving low-dose of corticosteroids (≤10 mg prednisone or equivalent) for at least 7 days prior to first dose of BAY 2927088 are eligible to enroll in Dose Escalation and Backfill.
Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion if all of the following criteria are met:
there is no evidence of progression (new or enlarging brain metastases) for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
Participants must be off or receiving low-dose of corticosteroids (≤10 mg prednisone or equivalent) for 7 days prior to first dose of BAY 2927088.
History of congestive heart failure (CHF) Class >II according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment or any clinically important abnormalities in rhythm, conduction or morphology or resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec).
Known human immunodeficiency virus (HIV), except as noted below: Participants with history of HIV infection are eligible at the Investigator's discretion provided that: • CD4+ T-cell (CD4+) counts are ≥ 350 cells/uL • The participant has been on established antiretroviral therapy (ART) for at least 4 weeks prior to the start of study drug and has an HIV viral load less than 400 copies/mL prior to start of the study treatment • The ART being used does not contain strong inducers or inhibitors of CYP3A4, and is not anticipated to cause overlapping toxicities with study drug • The participant has not had an opportunistic infection within the past 12 months
Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg]) and Hepatitis B virus [HBV] DNA).
Active Hepatitis C infection (positive anti-HCV Antibody and quantitative HCV RNA results greater than the lower limits of detection of the assay).
NOTE: Participants with history of chronic HBV or HCV infection are eligible at the Investigator's discretion provided that the disease is stable and sufficiently controlled under treatment.
Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first administration of study drug. Strong CYP3A4 inhibitors and inducers are prohibited during the study and until Safety FU (follow up) visit.
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There are 36 Locations for this study
Duarte California, 91010, United States
Atlanta Georgia, 30322, United States
Boston Massachusetts, 02215, United States
Detroit Michigan, 48202, United States
Buffalo New York, 14203, United States
New York New York, 10016, United States
Houston Texas, 77030, United States
Wuhan Hubei, 43002, China
Changsha Hunan, 41001, China
Nanjing Jiangsu, 21000, China
Chengdu Sichuan, 61004, China
Hangzhou Zhejiang, 31002, China
Beijing , 10014, China
Shanghai , 20003, China
Bordeaux Cedex , 33076, France
PARIS cedex 5 , 75248, France
Villejuif Cedex , 94805, France
Shatin , , Hong Kong
Napoli Campania, 80131, Italy
Pordenone Friuli-Venezia Giulia, 33081, Italy
Roma Lazio, 00168, Italy
Kashiwa Chiba, 277-8, Japan
Sunto Shizuoka, 411-8, Japan
Chuo-ku Tokyo, 104-0, Japan
Yonago Tottori, 683-8, Japan
Osaka , 541-8, Japan
Seongnam-si Gyeonggido, 13620, Korea, Republic of
Seoul Seoul Teugbyeolsi, 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 05505, Korea, Republic of
Singapore , 11907, Singapore
Singapore , 16961, Singapore
L'Hospitalet de Llobregat Barcelona, 08907, Spain
Barcelona , 08035, Spain
Madrid , 28040, Spain
Taichung , 40705, Taiwan
Taipei , 100, Taiwan
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