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

Study Identifier:
21607
CT.gov Identifier:
NCT05099172
EudraCT Identifier:
2021-003022-77
EU Trial (CTIS) Number:
2023-503795-24-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

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. To study the action of BAY2927088 against the cancer To determine the safety and tolerability of oral administration of BAY 2927088; To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY 2927088; To characterize the pharmacokinetics (PK) of BAY 2927088; To Assess preliminary antitumor activity of BAY 2927088; Determine Phase II recommended dose (RP2D) of BAY 2927088 To evaluate the safety, pharmacokinetics and preliminary efficacy of BAY 2927088 in adult patients with advanced NSCLC harboring HER2 or EGFR. Plasma samples were collected at baseline and several on-treatment time points for longitudinal ctDNA profiling using next-generation sequencing (NGS; Oncomine Precision Assay). To report updated results of BAY 2927088 from an expansion cohort of patients with HER2-mutant NSCLC naïve to HER2-targeted therapy enrolled in the SOHO-01 study. Study objectives included safety and anti-tumor activity (RECIST v1.1). Safety was assessed using MedDRA v27.0. The objective of the expansion phase of the study was to determine the safety, tolerability, and pharmacokinetics of BAY 2927088 in patients with HER2-mutant NSCLC. To report safety and efficacy data from 2 cohorts of the ongoing, open-label, multicenter Phase I/II SOHO-01 trial.

The main objectives of this trial are to see how safe the BAY2927088 is, how it affects the body (tolerability), how the BAY2927088 moves through the body and is eliminated from the body, and the maximum amount of BAY2927088 participants in the trial can consume without feeling too many side effects

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Non-Small Cell Lung Cancer
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Dose escalation Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD. Drug: BAY2927088_formulation A Oral administration Drug: BAY2927088_formulation B_1 Oral administration Drug: BAY2927088_formulation B_2 Oral administration Experimental: Backfill Dose Escalation and Backfill run concurrently Drug: BAY2927088_formulation A Oral administration Drug: BAY2927088_formulation B_1 Oral administration Drug: BAY2927088_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 dose level that has been evaluated in Escalation/Backfill in at least 9 participants and considered safe or at any other dose levels that are below the highest dose level that is considered safe. Drug: BAY2927088_formulation B_1 Oral administration Drug: BAY2927088_formulation B_2 Oral administration Experimental: Extension part Initiation of the Extension part will depend on the benefit-risk profile observed during Dose Expansion. Additionally, enrollment may be prematurely terminated based on emerging data at the discretion of the Sponsor. Drug: BAY2927088_formulation B_1 Oral administration Drug: BAY2927088_formulation B_2 Oral administration Experimental: Extension part The enrollment of the Extension part may be initiated once all ongoing participants from the corresponding Expansion cohort (participants within the same Group) have at least 12 weeks of treatment (corresponding to 2 post-baseline efficacy assessments) or discontinue treatment. Drug: BAY2927088_formulation B_1 Oral administration Drug: BAY2927088_formulation B_2 Oral administration Chinese common name: BAY 2927088 solution English common name: BAY 2927088 solution Dosage form: Oral solution Specification: 0.5% Dosage: 10 mg QD Duration: 21 days in a cycle until disease progression Dosage form: oral solution Specification: 0.5% Dosage: 20mg QD Medication Duration: 21 days in a cycle until disease progression Dosage Form: Tablet Specification: 20mg Dosage: 20mg BID Medication Duration: 21 days a cycle Dosage Form: Tablet Specification: 20mg Dosage: 40mg BID Medication Duration: 21 days a cycle WCLC 2024: Patients received oral BAY 2927088 20 mg twice daily. (Cohort D) and (Cohort E) - Both cohorts received oral sevabertinib 20 mg twice daily.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • 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:
    • 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).
    Exclusion 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, 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 exceptions:
    • Participants with treated brain metastases that are asymptomatic at screening and who are off or receiving low-dose 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/Extension (with the exception of Group G) 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 corticosteroids (≤10 mg prednisone or equivalent) for 7 days prior to first dose of BAY2927088.
    • 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.
    • Expansion Group G only: Participants with active (new or progressing) clinically stable brain metastases who do not require immediate CNS-directed treatment as per Investigator's 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 BAY2927088 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:
    • 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.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer