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An open label, first-in-human study of BAY 2927088 in participants with advanced non-small cell lung cancer (NSCLC) harboring an EGFR and/or HER2 mutation

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)

Tanigawa Takahiko

Bayer Yakuhin, Ltd.

2-4-9 Umeda, Kita-ku, Osaka, Osaka

byl_ct_contact@bayer.com

Dedicated contact

Bayer Yakuhin, Ltd.

2-4-9 Umeda, Kita-ku, Osaka, Osaka

+81-6-6133-6363

byl_ct_contact@bayer.com

Not Recruiting

July. 27, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- 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 (or, for participants in Expansion Group G, for RANO-BM 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) > 50mL/min per 1.73 m2 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).

- 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 leptomeningeal disease (symptomatic or asymptomatic), 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:
1. Participants with treated brain metastases that are asymptomatic atscreening and whoare off or receivinglow-dosecorticosteroids (<=10mg prednisone orequivalent) for atleast 7 days prior to first dose of BAY 2927088 are eligible to enroll in DoseEscalation and Backfill.
2. Participants with treated brain metastases that are asymptomatic at screening are eligible in Dose Expansion/Extension (with the exception of Group G) if all of the following criteria are met:
a. 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.
b. Participants must be off or receiving low-dose corticosteroids (<=10 mg prednisone or equivalent) for 7 days prior to first dose of BAY 2927088.
3. Participants with history of spinal cord compression >3 months from definitive therapy and stable by imaging (MRI or CT) during the screening period and clinically asymptomatic
4. Expansion Group G only: Participants with active (new or progressing) clinically stable brain metastases who do not require immediate CNS-directed treatment as per Investigators judgement and who are off or receiving low-dose corticosteroids (<=10 mg prednisone or equivalent such as <= 1.5 mg/day dexamethasone) in the 7 days prior to first dose of BAY 2927088 are eligible.
- History of congestive heart failure (CHF) Class >II according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment (e.g.ventricular arrhythmias,atrial fibrillation) 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 Investigators 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 Investigators 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.

Both

Advanced Non-Small Cell Lung Cancer
EGFR Mutation
HER2 Mutation

Experimental: Dose escalation
Doses of BAY 2927088 will be increased in a stepwise fashion up to the MTD orMAD.
Drug: BAY 2927088_formulation A, Oral administration
Drug: BAY 2927088_formulation B_1, Oral administration
Drug: BAY 2927088_formulation B_2, Oral administration

Experimental: Backfill
Dose Escalation and Backfill run concurrently
Drug: BAY 2927088_formulation A
Oral administration
Drug: BAY 2927088_formulation B_1
Oral administration
Drug: BAY 2927088_formulation B_2
Oral administration

Experimental: Dose expansion
Eight independent groups (group A, B1, B2,C, D, E, F, G) are planned. Dose Expansion may start at a doselevel that has been evaluated in Escalation/Backfi ll in at least 9participants and considered safeor at any other dose levels that are belowthe highest dose level that is considered safe.
Drug: BAY 2927088_formulation B_1
Oral administration
Drug: BAY 2927088_formulation B_2
Oral administration

Experimental: Extension part
Initiation of the Extension part will dependon the benefi t-risk profi le observed duringDose Expansion. Additionally, enrollmentmay be prematurely terminated based on emerging data at the discretion of theSponsor.
Drug: BAY 2927088_formulation B_1
Oral administration
Drug: BAY 2927088_formulation B_2
Oral administration

1. Number of participants with treatment-emergent adverse events (TEAEs)
[Time Frame: Up to 30 days after the last administration of study treatment]
2. Number of participants with treatment-emergent serious adverse events (TESAEs) [Time Frame: Up to 30 days after the last administration of study treatment]
3. Severity of TEAEs
[Time Frame: Up to 30 days after the last administration of study treatment]
4. Severity of TESAEs
[Time Frame: Up to 30 days after the last administration of study treatment]
5. Number of participants who discontinue study treatment due to an AE
[Time Frame: About 4 years (Up to the end of study treatment)]
6. Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY 2927088 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]
7. Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY 2927088 in the DLT observation period in Dose Escalation (including participants from Backfill)
[Time Frame: At the end of Cycle 1 of a 21-day cycle]
8. Cmax of BAY 2927088
Cmax: Maximum/peak concentration
[Time Frame: Cycle 1, Day 1 (Cycle duration is 21 days)]
9. AUC(0-24) of BAY 2927088 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)]
10. AUC(0-12) of BAY 2927088 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)]
11. Cmax,md of BAY 2927088
Cmax,md: Cmax after multiple dose administrations
[Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days)]
12. AUC(0-24)md of BAY 2927088 for QD
AUC(0-24)md: AUC(0-24) after multiple dose administrations
[Time Frame: Cycle 1, Day 15 (Cycle duration is 21 days)]
13. AUC(0-12)md of BAY 2927088 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)]
14. Overall response rate(ORR) per ResponseEvaluation Criteria inSolid Tumors, version 1.1(RECIST v1.1) by blinded independent central review (BICR) inextension part
[Time Frame: From thestart of the studytreatment up to 12months]

1. 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]
2. Recommended phase 2 dose (RP2D) of BAY 2927088
[Time Frame: About 1.5 years]
3. ORR per RECIST v1.1 by Investigator assessment in extension part
[Time Frame: From the start of the study treatment up to 12 months]
4. 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]
5. 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]
6. 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]
7. Overall survival (OS) in extension part
[Time Frame: From the start of the study treatment up to 12 months]
8. 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]

+81-3-3542-2511

July. 04, 2022

No

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