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)
Advanced Non-small Cell Lung Cancer, EGFR Mutation, HER2 Mutation
About this trial
This is an interventional treatment trial for Advanced Non-small Cell Lung Cancer
Eligibility Criteria
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.
- 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).
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 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).
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.
Sites / Locations
- Banner MD Anderson Cancer Center
- City of Hope National Medical CenterRecruiting
- City of Hope-Cancer DepartmentRecruiting
- Emory UniversityRecruiting
- The Center for Cancer and Blood DisordersRecruiting
- Dana-Farber Cancer InstituteRecruiting
- Henry Ford Health System | Brigitte Harris Cancer PavilionRecruiting
- Roswell Park Comprehensive Cancer Center
- NYU Langone Health
- Tennessee OncologyRecruiting
- University of Texas MD Anderson Cancer CenterRecruiting
- Virginia Cancer Specialists, PCRecruiting
- UZ Leuven GasthuisbergRecruiting
- AZ Delta | Clinical Trial Center - PneumologyRecruiting
- Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica
- Hospital de Base da Fundação F M S J Rio Preto
- Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department
- Fujian Cancer HospitalRecruiting
- Harbin Medical University Cancer HospitalRecruiting
- Union Hospi, Tongji Med College, Huazhong Univ. Scien&TechRecruiting
- Hunan Cancer HospitalRecruiting
- NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med SchoolRecruiting
- Qilu Hospital of Shandong UniversityRecruiting
- West China Hospital Sichuan UniversityRecruiting
- Sir Run Run Shaw Hospital, Zhejiang University School of MedRecruiting
- Zhejiang Cancer HospitalRecruiting
- Beijing Cancer HospitalRecruiting
- Beijing HospitalRecruiting
- Shanghai Chest Hospital, Shanghai Jiaotong UniversityRecruiting
- Institut Bergonié - Unicancer Nouvelle AquitaineRecruiting
- Centre Léon BérardRecruiting
- Institut Curie - Ulm - ParisRecruiting
- Institut de Cancérologie de l'Ouest - Saint HerblainRecruiting
- Institut Gustave Roussy - Département de Médecine Oncologique
- Queen Mary HospitalRecruiting
- Prince of Wales Hospital Hong KongRecruiting
- Clalit Health Services Rabin Medical Center-Beilinson CampusRecruiting
- Chaim Sheba Medical CenterRecruiting
- Istituto Nazionale Tumori IRCCS Fondazione G.PascaleRecruiting
- A.O.U. di ParmaRecruiting
- IRCCS Centro di Riferimento Oncologico (CRO)Recruiting
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSRecruiting
- Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.Recruiting
- Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting
- IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)Recruiting
- A.O.U. San Luigi GonzagaRecruiting
- Aichi Cancer Center HospitalRecruiting
- National Cancer Center Hospital EastRecruiting
- National Hospital Organization Shikoku Cancer CenterRecruiting
- Hokkaido University HospitalRecruiting
- Kanagawa Cancer CenterRecruiting
- Shizuoka Cancer Center
- National Cancer Center HospitalRecruiting
- Tottori University HospitalRecruiting
- Osaka International Cancer InstituteRecruiting
- Chungbuk National University HospitalRecruiting
- Seoul National University Bundang HospitalRecruiting
- St.Vincent's HospitalRecruiting
- Seoul National University HospitalRecruiting
- Asan Medical CenterRecruiting
- Severance Hospital, Yonsei University Health SystemRecruiting
- Nederlands Kanker InstituutRecruiting
- Erasmus Medisch Centrum
- Uniwersyteckie Centrum KliniczneRecruiting
- SP ZOZ USK im. WAM UM w Lodzi - Centralny Szpital WeteranowRecruiting
- CHULN - H. Sta.Maria (Centro de Investigacao Clinica)
- IPO PortoRecruiting
- National University HospitalRecruiting
- National Cancer Center SingaporeRecruiting
- Institut Català d'Oncologia HospitaletRecruiting
- Ciutat Sanitaria i Universitaria de la Vall d'HebronRecruiting
- Hospital Quiron DexeusRecruiting
- Fundacion Jimenez Diaz (Clinica de la Concepcion)Recruiting
- Centro Integral Oncológico Clara CampalRecruiting
- Hospital Universitari i Politècnic La FeRecruiting
- Taichung Veterans General HospitalRecruiting
- National Cheng Kung University HospitalRecruiting
- National Taiwan University HospitalRecruiting
- Chang Gung Memorial Hospital at Linkou
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Dose escalation
Backfill
Dose expansion
Dose Escalation and Backfill run concurrently
Dose Expansion is initiated after Dose Escalation and Backfill.