A Phase 2 Open-label Basket Study to Evaluate the Efficacy and Safety of Orally Administered Reversible Tyrosine Kinase Inhibitor BAY 2927088 in Participants With Metastatic or Unresectable Solid Tumors With HER2-activating Mutations
Overview
- Phase
- Phase 2
- Intervention
- BAY2927088
- Conditions
- Not specified
- Sponsor
- Bayer
- Enrollment
- 111
- Locations
- 107
- Primary Endpoint
- Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR
- Status
- Recruiting
- Last Updated
- 24 days ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
BAY2927088
Adult participants with metastatic or unresectable solid tumors with HER-2 activating mutations including: colorectal, biliary tract, bladder, cervical, endometrial, breast, and other solid tumor types. Participants will receive BAY2927088 20 mg BID until disease progression per RECICST 1.1, unacceptable toxicity, or until any other withdrawal criteria. RECIST 1.1 = Response Evaluation Criteria in Solid Tumors, version 1.1; BID: twice a day
Intervention: BAY2927088
Outcomes
Primary Outcomes
Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR
Time Frame: 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 Outcomes
- 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)
- 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))
- 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)
- 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 ≥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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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))
- 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)
- 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)
- 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))
- 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))
- 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))