Advanced Solid Tumors, HER2 Mutation
Conditions
Keywords
Colorectal cancer, CRC, Biliary tract cancer, BTC, Bladder cancer, Cervical cancer, Endometrial cancer, Sarcoma, Gastrointestinal stromal tumor, GIST, Breast cancer, Gastrointestinal cancer, GI cancer, Gastric cancer, Esophageal cancer, Gallbladder cancer, Pancreatic cancer, Ovarian Cancer, Salivary cancer, Ampullary cancer, Urothelial cancer, HER2 mutant cancer
Brief summary
Researchers are looking for a better way to treat people who have solid tumors with HER2-activating mutations. Before a treatment can be approved for people to take, researchers do clinical trials to better understand its safety and how it works. In this trial, the researchers want to learn how well BAY2927088 (sevabertinib) works in people with different types of solid tumors with HER2 mutations. These include tumors in the colon or rectum, the uterus and the cervix (lower part of the uterus), the breast, the bladder, and the biliary tract (includes gall bladder and bile ducts) as well as other types of solid tumors with the exception of people with advanced non-small cell lung cancer (NSCLC). Solid tumors may have specific changes or mutations to a gene called human epidermal growth receptor-2 (HER2). This leads to the formation of an abnormal form of HER2 protein in the cancer cells, resulting in increased cell growth. The study treatment, BAY2927088, is expected to block the abnormal HER2 protein which may stop the spread of cancer. The trial will include about 111 participants who are at least 18 years old. All the participants will take 20 mg of BAY2927088 as tablets by mouth. The participants will take treatments in 3-week periods called cycles. These 3-week cycles will be repeated throughout the trial. The participants can take BAY2927088 until their cancer gets worse, until they have medical problems, or until they leave the trial. During the trial, the doctors will take imaging scans of different parts of the body to study the spread of cancer and will check heart health using echocardiogram or cardiac magnetic resonance imaging (MRI) and electrocardiogram (ECG). The doctors will also take blood and urine samples and do physical examinations to check the participants' health. They will ask questions about how the participants are feeling and if they have any medical problems.
Interventions
DRUGBAY2927088
tablet, oral
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented histologically or cytologically confirmed locally advanced, unresectable or metastatic solid tumor cancer (colorectal carcinoma; biliary tract cancer; bladder and urothelial tract cancer; cervical cancer; endometrial cancer; breast cancer; other solid tumor cancer, excluding NSCLC) * Participant must be ≥18 years of age or over the legal age of consent * Patients who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments * Documented activating HER2 mutation * At least one measurable lesion that would qualify as a target lesion by RECIST 1.1 criteria
Exclusion criteria
* Primary diagnosis of non-small cell lung cancer (NSCLC) * Prior treatment with a HER2 tyrosine kinase inhibitor (TKI) * Active brain metastases * Uncontrolled, severe, intercurrent illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) per RECIST 1.1 by BICR. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \<10 mm. PR is defined as a ≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) per RECIST 1.1 as assessed by BICR | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | DOR is defined as the time from date of first documented complete or partial response (if confirmed) until the earliest date of progressive disease (PD) per RECIST 1.1 as assessed by BICR, or death from any cause, whichever occurs first. PD is defined as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR) |
| Time to response (TTR) per RECIST 1.1 as assessed by BICR | From first participant enrolled until end of treatment or end of imaging active follow-up (up to approximately 3 years) | TTR is defined as the time from the start of study treatment until the date of first documented complete or partial response (if confirmed) per RECIST 1.1 as assessed by BICR. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BICR = blinded independent central review (BICR) |
| ORR per RECIST 1.1 as assessed by the investigator | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | ORR is defined as the proportion of participants with a best overall response of confirmed CR or confirmed PR per RECIST 1.1 by investigator. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1 |
| Disease control rate (DCR) per RECIST 1.1 as assessed by BICR | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | DCR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) or stable disease (SD), by the BICR per RECIST 1.1. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. |
| DCR ≥12 weeks per RECIST 1.1 as assessed by BICR | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | Defined as the proportion of participants with a best overall response of confirmed CR or PR or SD (for at least 12 weeks following the first study intervention), by the BICR per RECIST 1.1. |
| Progression-free survival (PFS) per RECIST 1.1 as assessed by BICR | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | Defined as the time from date of start of treatment until the earliest date of PD per RECIST 1.1 as assessed by the BICR, or death from any cause, whichever occurs first. |
| Disease control rate (DCR) per RECIST 1.1 as assessed by the investigator | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | Defined as the proportion of participants with a best overall response of confirmed CR or PR or SD, by the investigator per RECIST 1.1. |
| DCR ≥12 weeks per RECIST 1.1 as assessed by the investigator | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | Defined as the proportion of participants with a best overall response of confirmed CR or PR or SD (for at least 12 weeks following the first study intervention), by the investigator per RECIST 1.1. |
| Progression-free survival (PFS) per RECIST 1.1 as assessed by the investigator | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | Defined as the time from date of start of treatment until the earliest date of PD per RECIST 1.1 as assessed by the investigator, or death from any cause, whichever occurs first |
| DOR per RECIST 1.1 as assessed by the investigator | From start of study intervention until the first documented progression, or death from any cause, or end of study (up to approximately 3 years), whichever comes first | DOR is defined as the time from date of first documented complete or partial response (if confirmed) until the earliest date of PD per RECIST 1.1 as assessed by the investigator, or death from any cause, whichever occurs first. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1 |
| TTR per RECIST 1.1 as assessed by the investigator | From first participant enrolled until end of treatment or end of imaging active follow-up (up to approximately 3 years) | TTR is defined as the time from the start of study treatment until the date of first documented complete or partial response (if confirmed) per RECIST 1.1 as assessed by the investigator. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1 |
| Overall survival (OS) | From start of study intervention until death from any cause, or end of study (up to approximately 3 years), whichever comes first | Defined as the time from the start of study treatment to the date of death from any cause. |
| Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) per CTCAE v 5.0, categorized by severity, including number of participants who discontinue study treatment due to an AE | From first participant enrolled until up to 30 days after the last administration of study treatment | From first administration of study intervention up to 30 days after the last dose of study intervention. |
| Time to deterioration in EORTC QLQ-C30 physical functioning domain score | Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years) | The EORTC QLQ-C30 is a multi-dimensional validated cancer-specific quality of life (QoL) questionnaire developed by the EORTC Study Group on QoL for use in international clinical trial settings. The EORTC QLQ-C30 will be used to evaluate the time to deterioration in the physical functioning domain score. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 |
| Change from baseline in EORTC QLQ-C30 physical functioning domain score | Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years) | The EORTC QLQ-C30 is a multi-dimensional validated cancer-specific quality of life (QoL) questionnaire developed by the EORTC Study Group on QoL for use in international clinical trial settings. The EORTC QLQ-C30 will be used to evaluate the change from baseline in the physical functioning domain score. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 |
| Change from baseline in EORTC QLQ-C30 global health status/quality of life (QoL) | Baseline and up until end of treatment or end of imaging active follow-up (up to approximately 3 years) | The EORTC QLQ-C30 is a multi-dimensional validated cancer-specific quality of life (QoL) questionnaire developed by the EORTC Study Group on QoL for use in international clinical trial settings. The EORTC QLQ-C30 will be used to evaluate the change from baseline in global health status/QoL. EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 |
Countries
Australia, Canada, China, Denmark, France, Italy, Japan, South Korea, Spain, Switzerland, United States
Contacts
CONTACTBayer Clinical Trials Contact
Outcome results
None listed