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)
Condition(s) studied
Investigational drug(s) / intervention(s)
BAY2927088_formulation A: Oral administration
BAY2927088_formulation B_1: Oral administration
BAY2927088_formulation B_2: Oral administration
BAY2927088_formulation B_3: Oral administration
Study summary
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. The study treatment, sevabertinib (BAY2927088), is expected to block the mutated EGFR and HER2 proteins which may stop the spread of NSCLC.
The main purpose of this study is to learn:
Escalation, Backfill, and Expansion Part:
* How safe is BAY2927088 for the participants?
* What is the highest dose of BAY2927088 that can be tolerated (maximum tolerated dose) by or given to (maximum administered dose) the participants?
* How does BAY2927088 move into, through, and out of the bodies of the participants?
For this, the researchers will measure the followings:
* The number of participants with medical problems, also called adverse events and serious adverse events, and their severity
* The number of participants who discontinue study treatment due to an adverse event.
* The highest dose of BAY2927088 that the participants can take without having adverse events (maximum tolerated dose (MTD)) or the maximum dose that is tested and found to be safe for the participants in case MTD cannot be found out (maximum administered dose (MAD)) of BAY2927088
* Number of participants experiencing adverse events that prevent an increase in the dose of BAY2927088 (dose-limiting toxicities (DLTs)) at each dose level
* The (average) total level of BAY2927088 in the blood (also called AUC) after receiving single or multiple doses of BAY2927088
* The (average) highest level of BAY2927088 in the blood (also called Cmax) after receiving a single or multiple doses of BAY2927088 Extension Part
* How well does BAY2927088 work in participants?
For this, the researchers will measure the following:
• Percentage of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)). This will be assessed by doctors other than the study doctor.
This study has 4 parts:
* The escalation part aims to find the maximum daily amount (dose) of BAY2927088 that participants can receive.
* The backfill part aims to test the doses of BAY2927088 that are considered safe in the escalation part by giving it to more participants. This will help find optimal doses of BAY2927088 that work well and are safe to be tested in the next part.
* The expansion part aims to determine the dose of BAY2927088 to be tested in further studies.
* The extension part aims to determine whether the selected dose of BAY2927088 from the expansion part works well.
The participants in this study will take the study treatment BAY2927088 in 3-week periods called "cycles". They will in general take BAY2927088 once or twice daily as a liquid/tablet by mouth until their cancer gets worse, they have medical problems, they leave the study, or the study is terminated. Participants will have no more than 5 visits per cycle.
During the study, the study team will:
* take blood and urine samples,
* check the status of the cancer by doing computed tomography (CT) or magnetic resonance imaging (MRI) scans,
* 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 considered "serious" when it leads to death, puts the participant's life at risk, requires hospitalization, causes disability, causes a baby being born with medical problems, or is medically important.
Eligibility
Primary outcome measure(s)
- Number of participants with treatment-emergent adverse events (TEAEs) — Up to 30 days after the last administration of study treatment
- Number of participants with treatment-emergent serious adverse events (TESAEs) — Up to 30 days after the last administration of study treatment
- Severity of TEAEs — Up to 30 days after the last administration of study treatment
- Severity of TESAEs — Up to 30 days after the last administration of study treatment
- Number of participants who discontinue study treatment due to an AE — About 4 years (Up to the end of study treatment)
- Maximum tolerated dose (MTD) or maximum administered dose (MAD) of BAY2927088 within the DLT observation period in Dose Escalation (including participants from Backfill qualifying for the MTD population) — At the end of Cycle 1 of a 21-day cycle
- Number of participants experiencing dose-limiting toxicities (DLTs) at each dose level associated with administration of BAY2927088 in the DLT observation period in Dose Escalation (including participants from Backfill) — At the end of Cycle 1 of a 21-day cycle
In Dose Escalation (including participants from Backfill) - Cmax of BAY2927088 — Cycle 1, Day 1 (Cycle duration is 21 days)
Cmax: Maximum/peak concentration - AUC(0-24) of BAY2927088 for QD — 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 — 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 — Cycle 1, Day 15 (Cycle duration is 21 days)
Cmax,md: Cmax after multiple dose administrations - AUC(0-24)md of BAY2927088 for QD — 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 — Cycle 1, Day 15 (Cycle duration is 21 days)
If applicable AUC(0-12)md: AUC(0-12) after multiple dose administrations - Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR) in extension part — From the start of the study treatment up to 12 months
Trial sites (92)
| Facility | City | Region | Status |
|---|---|---|---|
| Banner MD Anderson Cancer Center at Banner Gateway Medical Center | Gilbert | Arizona | Completed |
| City of Hope - Duarte Cancer Center | Duarte | California | Completed |
| Emory Winship Cancer Institute | Atlanta | Georgia | Active Not Recruiting |
| The Center for Cancer and Blood Disorders | Bethesda | Maryland | Withdrawn |
| Dana-Farber Cancer Institute - Oncology Department | Boston | Massachusetts | Completed |
| Brigette Harris Cancer Pavilion at Henry Ford Cancer Center - Detroit | Detroit | Michigan | Completed |
| Roswell Park Comprehensive Cancer Center | Buffalo | New York | Withdrawn |
| Tennessee Oncology - Nashville Centennial Clinic | Nashville | Tennessee | Recruiting |
| The University of Texas MD Anderson Cancer Center - Texas Medical Center | Houston | Texas | Active Not Recruiting |
| Inova Schar Cancer Insitute - Inova Fairfax Hospital | Fairfax | Washington | Withdrawn |
| Virginia Cancer Specialists, PC - Fairfax | Fairfax | Washington | Completed |
| UZ Leuven Gasthuisberg - Pneumology Department | Leuven | Flemish Brabant | Active Not Recruiting |
| AZ Delta | Clinical Trial Center - Pneumology | Roeselare | West Flanders | Active Not Recruiting |
| Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica | Natal | Rio Grande do Norte | Active Not Recruiting |
| Hospital de Base | Funfarme - Centro Integrado de Pesquisa - Cardiologia | São José do Rio Preto | São Paulo | Withdrawn |
| Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department | São Paulo | Brazil | Withdrawn |
| Beijing Cancer Hospital - Oncology Department | Beijing | Beijing Municipality | Active Not Recruiting |
| Beijing Hospital | Beijing | Beijing Municipality | Active Not Recruiting |
| Fujian Cancer Hospital | Fuzhou | Fujian | Active Not Recruiting |
| Harbin Medical University Cancer Hospital | Harbin | Heilongjiang | Terminated |
| Union Hospi, Tongji Med College, Huazhong Univ. Scien&Tech | Wuhan | Hubei | Active Not Recruiting |
| Hunan Cancer Hospital - Oncology Department | Changsha | Hunan | Active Not Recruiting |
| NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School | Nanjing | Jiangsu | Active Not Recruiting |
| Zhejiang University School of Medicine - Taizhou Hospital of Zhejiang Province | Taizhou | Jiangsu | Active Not Recruiting |
| Qilu Hosp., Shandong Univ. | Jinan | Shandong | Terminated |
| Shandong University - Shandong Cancer Hospital | Jinan | Shandong | Active Not Recruiting |
| Shanghai Chest Hospital, Shanghai Jiaotong University | Shanghai | Shanghai Municipality | Active Not Recruiting |
| West China Hospital Sichuan University | Chengdu | Sichuan | Active Not Recruiting |
| Sir Run Run Shaw Hospital, Zhejiang Univ. School of Medicine - Oncology Department | Hangzhou | Zhejiang | Active Not Recruiting |
| Zhejiang Cancer Hospital | Hangzhou | Zhejiang | Active Not Recruiting |
| UNICANCER - Centre Leon-Berard (CLB) - Medical oncology | Lyon | Auvergne-Rhône-Alpes | Active Not Recruiting |
| Institut Bergonie - Unicancer Nouvelle Aquitaine - Service Oncologie medicale | Bordeaux | New Aquitaine | Completed |
| Hopital Nord Laennec - Oncologie medicale thoracique et digestive | Nantes | Pays de la Loire Region | Active Not Recruiting |
| Institut de Cancerologie Ouest - Saint Herblain - Oncologie medicale | Saint-Herblain | Pays de la Loire Region | Active Not Recruiting |
| AP-HM - Hopital de la Timone - Centre d'Essais en Cancerologie | Marseille | Provence-Alpes-Côte d'Azur Region | Withdrawn |
| Institut Curie - Paris - Oncologie medicale | Paris | Île-de-France Region | Completed |
| Gustave Roussy - Departement Oncologie-Radiotherapie | Villejuif | Île-de-France Region | Completed |
| Prince of Wales Hospital | Hong Kong | Hong Kong SAR | Active Not Recruiting |
| Queen Mary Hospital | Hong Kong | Hong Kong SAR | Active Not Recruiting |
| Hong Kong United Oncology Centre | Kowloon | Hong Kong | Recruiting |
+ 52 more sites — see the full list on the official registry below.
More Bayer trials in Italy
Other trials for the same condition
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT05099172 on ClinicalTrials.gov ↗ ← All trials in Italy