BAY2927088 for Cancer

(panSOHO Trial)

Recruiting at 57 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

Trial Summary

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.

What makes the drug BAY2927088 unique for cancer treatment?

BAY2927088 is unique because it targets both CDK4 and CDK2 by inhibiting the phosphorylation of p27, a protein that regulates these kinases. This dual inhibition approach is designed to overcome resistance seen with other treatments like palbociclib, potentially leading to a more effective and long-lasting response in cancer cells. ^{1 2 3 4 5}

What is the purpose of this trial?

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 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 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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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, 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

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Tyrosine Phosphorylation of p27Kip1 Correlates with Palbociclib Responsiveness in Breast Cancer Tumor Cells Grown in Explant Culture. [2020]

3. China pubmed.ncbi.nlm.nih.gov

[Prognostic significance of cyclin-dependent kinase inhibitor p27kip1 expression in human breast cancer]. [2006]

4. United States pubmed.ncbi.nlm.nih.gov

Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Akt-dependent T198 phosphorylation of cyclin-dependent kinase inhibitor p27kip1 in breast cancer. [2021]