BAY2927088 for Cancer

(panSOHO Trial)

Recruiting at 103 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bayer

Must not be taking: HER2 TKIs

Disqualifiers: NSCLC, Brain metastases, Severe illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3-week cycles, up to approximately 3 years

111 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BAY2927088 for individuals with solid tumors that have changes in the HER2 gene. Researchers aim to determine if this treatment can halt cancer growth by blocking the abnormal HER2 protein in cancer cells. The trial includes participants with specific tumor types, such as those in the colon, breast, and bladder, provided they have not had a specific type of lung cancer or certain other treatments. Participants must have a confirmed HER2 mutation and have tried other standard therapies without success. The goal is to find a more effective way to treat these cancers. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial doctors to get a clear answer.

Is there any evidence suggesting that BAY2927088 is likely to be safe for humans?

Research shows that BAY2927088, a treatment under study for certain types of cancer, has a manageable safety profile. In earlier studies with patients who had advanced non-small cell lung cancer, the drug was generally well-tolerated. Participants experienced some side effects, but these were usually mild. This suggests that the treatment might be safe for other types of cancer with similar HER2 mutations. However, since this trial is in an early stage, more research is needed to fully understand the safety of BAY2927088 in people with different kinds of solid tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

BAY2927088 is unique because it specifically targets HER-2 activating mutations found in various solid tumors, such as colorectal, biliary tract, and breast cancers. While many current treatments for these cancers focus on broader approaches like chemotherapy or general HER-2 inhibitors, BAY2927088 zeroes in on these specific mutations, potentially offering a more precise attack on cancer cells. Researchers are excited because this targeted approach could lead to fewer side effects and a more effective treatment for patients with these mutations, offering new hope for those whose cancers have been resistant to standard therapies.

What evidence suggests that BAY2927088 might be an effective treatment for solid tumors with HER2 mutations?

Research has shown that BAY2927088, also known as sevabertinib, can block abnormal HER2 proteins, potentially stopping cancer from spreading. Previous studies found that BAY2927088 worked quickly and effectively in patients with HER2 mutations, particularly in non-small cell lung cancer. This treatment is a type of tyrosine kinase inhibitor, targeting and disrupting proteins that aid cancer cell growth. The safety of BAY2927088 is considered manageable, and it has led to high response rates and long-lasting disease control in patients previously treated for HER2-mutant cancers. While most data comes from lung cancer studies, these results are promising for other solid tumors with HER2 mutations. Participants in this trial will receive BAY2927088 to evaluate its effectiveness in various solid tumors with HER2 mutations. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors that have HER2 mutations, excluding those with advanced non-small cell lung cancer. Participants must be at least 18 years old and can have various tumor types such as in the colon, rectum, uterus, cervix, bladder, or biliary tract.

Inclusion Criteria

I've had all standard treatments for my cancer or there are no good options left.

My cancer is advanced and cannot be removed by surgery.

I have at least one tumor that can be measured for treatment response.

Exclusion Criteria

My primary diagnosis is non-small cell lung cancer.

I have been treated with a HER2-targeting drug before.

I do not have any severe illnesses that are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BAY2927088 in 3-week cycles until disease progression or unacceptable toxicity

3-week cycles, up to approximately 3 years

Regular visits for imaging scans, heart health checks, and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• BAY2927088

Trial Overview

The study tests BAY2927088 tablets taken orally to see if they're effective and safe in treating solid tumors with HER2 mutations. Patients will undergo treatment cycles every three weeks and continue until their condition worsens or side effects become too severe.

How Is the Trial Designed?

Group I: BAY2927088 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Bayer

Lead Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

The study identifies the pY88 biomarker as a potential predictor of response to cdk4-targeting drugs like palbociclib in breast cancer, suggesting that patients with low or absent pY88 levels are unlikely to benefit from this treatment.

By using dual IHC staining for p27 and pY88, researchers were able to stratify breast cancer biopsies and demonstrate that only tumors with detectable pY88 responded to palbociclib, indicating that this biomarker could help select appropriate patients for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine Phosphorylation of p27Kip1 Correlates with Palbociclib Responsiveness in Breast Cancer Tumor Cells Grown in Explant Culture. Gottesman, SRS., Somma, J., Tsiperson, V., et al.[2020]

Endogenous p27(kip1) is phosphorylated at the T198 site in breast cancer cells, which is not seen in normal mammary epithelial cells, indicating a potential biomarker for cancer progression.

The phosphorylation of p27(kip1) at T198 is regulated by the PI3K-PKB/Akt pathway, suggesting that targeting this pathway could influence the localization and function of p27(kip1) in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Akt-dependent T198 phosphorylation of cyclin-dependent kinase inhibitor p27kip1 in breast cancer. Motti, ML., De Marco, C., Califano, D., et al.[2021]

Inhibition of both CDK4 and CDK2 is necessary for a durable response in breast cancer treatment, as CDK2 can compensate for the loss of CDK4 activity when using palbociclib.

The novel strategy using the Brk-SH3 peptide, ALT, effectively inhibits both CDK4 and CDK2 by preventing the phosphorylation of p27Kip1, leading to a potent and long-lasting cell-cycle arrest, and shows promise in enhancing the efficacy of existing treatments like palbociclib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation Induces a Potent and Durable Response in Breast Cancer Cells. Patel, P., Tsiperson, V., Gottesman, SRS., et al.[2019]

In a study of 181 breast cancer patients, low expression of the protein p27kip1 was found in 66.9% of cases, and higher levels were associated with better disease-free survival, indicating a potential link between p27kip1 levels and tumor behavior.

Despite the correlation between p27kip1 expression and various tumor characteristics, it was not determined to be an independent prognostic factor, suggesting that while it may influence cancer progression, other factors also play significant roles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prognostic significance of cyclin-dependent kinase inhibitor p27kip1 expression in human breast cancer]. Wu, J., Shen, Z., Shao, Z.[2006]

The study identifies Brk (breast tumor-related kinase) as a key regulator of cdk4 activity through its interaction with p27, highlighting the importance of pY88 phosphorylation in cancer progression.

Brk is overexpressed in 60% of breast carcinomas, suggesting it plays a significant role in promoting tumor growth by modulating cdk4 activity, indicating that p27 may function as an oncoprotein rather than just a tumor suppressor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4. Patel, P., Asbach, B., Shteyn, E., et al.[2022]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06760819

NCT06760819 | A Study to Learn More About How Well ...

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 ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA8598

Safety and anti-tumor activity of BAY 2927088 in patients ...

BAY 2927088 led to rapid, substantial, and durable responses in pts with pretreated HER2-mutant NSCLC. The safety profile was consistent with previously ...

3.

bayer.com

bayer.com/en/us/news-stories/non-small-cell-lung-cancer

New results from the Investigational agent BAY 2927088 in ...

BAY 2927088 is an oral, small molecule, tyrosine kinase inhibitor as a potential new targeted therapy for patients with non-small cell lung cancer (NSCLC) ...

4.

asco.org

asco.org/abstracts-presentations/ABSTRACT496140

SOHO-01: Safety and efficacy of BAY 2927088 in patients ...

The potent, reversible HER2 tyrosine kinase inhibitor BAY 2927088 has demonstrated manageable safety and anti-tumor activity in patients with advanced NSCLC.

5.

onclive.com

onclive.com/view/safety-and-efficacy-of-bay-2927088-in-patients-with-her2-mutant-nsclc-expansion-cohort-from-the-phase-i-ii-soho-01-study

Safety and Efficacy of BAY 2927088 in Patients with HER2- ...

The oral HER2-targeted tyrosine kinase inhibitor BAY 2927088 achieves high response rates and durable disease control in patients with pretreated HER2-mutant ...

6.

clinicaltrial.be

clinicaltrial.be/en/details/37510?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

First in Human Study of BAY2927088 in Participants Who ...

The study treatment, BAY2927088, is expected to block the mutated EGFR and HER2 proteins which may stop the spread of NSCLC. The main purpose of ...