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)

JRCT ID: jRCT2031220233

Registered date:31/07/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced Non-Small Cell Lung Cance
• Date of first enrollment: 27/07/2022
• Target sample size: 250
• Countries of recruitment: China,Japan,Hong Kong,Japan,Italy,Japan,Korea,Japan,Republic of Singapore,Japan,Spain,Japan,Taiwan,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: BAY2927088_formulation A, Oral administration
Drug: BAY2927088_formulation B_1, Oral administration
Drug: BAY2927088_formulation B_2, Oral administration

Outcome(s)

Primary Outcome

- Number of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 35 days after the last administration of study treatment ]
- Number of participants with treatment-emergent serious adverse events (TESAEs) [ Time Frame: Up to 35 days after the last administration of study treatment ]
- Severity of TEAEs [ Time Frame: Up to 35 days after the last administration of study treatment ]
- Severity of TESAEs [ Time Frame: Up to 35 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) within the DLT observation period [ Time Frame: At the end of Cycle 1 of a 21-day cycle ]
In Dose Escalation (including participants from Backfill)
- Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY2927088 [ Time Frame: At the end of Cycle 1 of a 21-day cycle ]
In Dose Escalation (including participants from Backfill)
- Cmax of BAY2927088 [ Time Frame: Cycle 1, Day 1 (Cycle duration is 21 days) ]
Cmax: Maximum/peak concentration
- AUC(0-24) of BAY2927088 for QD [ Time Frame: Cycle 1, Day 1 (Cycle duration is 21 days) ]
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)
- AUC(0-12) of BAY2927088 for BID [ Time Frame: Cycle 1, Day 1 (Cycle duration is 21 days) ]
If applicable. AUC(0-12): AUC from time 0 to 12 hours post dose. BID: Bis in die, 2 times daily.
- Cmax,md of BAY2927088 of BAY2927088 [ Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days) ]
Cmax,md: Cmax after multiple dose administrations
- AUC(0-24)md of BAY2927088 for QD [ Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days) ]
AUC(0-24)md: AUC(0-24) after multiple dose administrations
- AUC(0-12)md of BAY2927088 for BID [ Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days) ]
If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Histologically or cytologically confirmed advanced or metastatic NSCLC (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, fresh biopsy derived from a non-significant risk procedure can be considered at the Investigators discretion.
- 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:
a. 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.
b. Platelets >= 100 * 10*9 cells/L.
c. 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) > 40 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:
a. 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).
b. Aspartate transaminase and alanine transaminase <= 2.5 * ULN (or <= 5 * ULN if due to liver involvement by tumor).

Exclude criteria

- 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 and palliative radiation <= 14 days prior to the first dose of study drug. If irradiated, lesions must have demonstrated progression prior to be considered for evaluation as target lesions.
- 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 exception:
a. Participants with treated brain metastases are eligible in Dose Escalation, Backfill and Expansion if 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. In addition, participants must be requiring stable or decreasing dose of corticosteroids for 7 days prior to first dose of BAY2927088.
- 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).
- Participants with:
a. 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
b. Active Hepatitis B infection (positive for Hepatitis B surface antigen [HbsAg]) and Hepatitis B virus [HBV] DNA).
c. 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 (see Section 10.5) are prohibited during the study and until Safety FU (follow up) visit.

Related Information

• Primary Sponsor: Tanigawa Takahiko
• Secondary ID(s): NCT05099172