BAY2927088 for Non-Small Cell Lung Cancer

Not currently recruiting at 183 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bayer

Must not be taking: Strong CYP3A4 inhibitors, inducers

Disqualifiers: Brain metastases, Heart failure, HIV, others

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

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BAY2927088 for individuals with advanced non-small cell lung cancer (NSCLC) that has spread. The researchers aim to determine the safety and effectiveness of this treatment by blocking specific proteins (EGFR and HER2) that promote cancer growth. The trial will test different doses to identify the safest and most effective amount, while also observing the drug's movement through the body. Suitable candidates have NSCLC that has progressed after prior treatment and possess a specific mutation in their cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop all current medications. However, you must stop taking EGFR tyrosine kinase inhibitors at least 8 days before the trial and other systemic anti-cancer treatments at least 14 days before. Immunotherapy should be stopped 28 days prior. Also, avoid strong CYP3A4 inhibitors and inducers 14 days before and during the study.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study drug. Specifically, you must stop taking EGFR tyrosine kinase inhibitors at least 8 days before, and other systemic anti-cancer treatments at least 14 days before the first dose. Additionally, strong CYP3A4 inhibitors and inducers must be stopped 14 days prior and are not allowed during the study.

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

Research has shown that BAY2927088, a treatment designed to stop the spread of certain lung cancers, has a manageable safety profile. In previous studies, patients with advanced non-small cell lung cancer (NSCLC) tolerated BAY2927088 well up to a dose of 60 mg per day. While some side effects occurred, they were not severe enough to make the treatment unsafe at that level.

These early results suggest that most people can handle the treatment without serious problems. However, like any new treatment, some risks may still exist. The current study examines its safety more closely and aims to find the best dose for patients. ^{1 2 3 4 5}

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

Unlike the standard treatments for non-small cell lung cancer, which generally include chemotherapy, targeted therapy, and immunotherapy, BAY2927088 offers a novel approach. Researchers are excited about BAY2927088 because it has a unique mechanism of action that targets specific cancer pathways more precisely, potentially leading to better outcomes with fewer side effects. This treatment is designed to escalate and expand doses safely, which could optimize its effectiveness and safety profile compared to current options. This innovative approach is generating excitement as it may provide a more effective and targeted option for patients.

What evidence suggests that BAY2927088 might be an effective treatment for non-small cell lung cancer?

Research has shown that BAY2927088 may help treat non-small cell lung cancer (NSCLC), particularly in patients with specific genetic changes. This trial will evaluate BAY2927088 in various treatment arms, including dose escalation, dose expansion, backfill, and an extension part. Studies have found that BAY2927088 can quickly and effectively shrink tumors in patients with HER2-mutant NSCLC. This treatment blocks the mutated proteins that allow cancer cells to grow and spread. Patients in earlier studies experienced significant and lasting improvements, which is promising. Overall, the treatment has demonstrated a manageable safety profile, making it a potential new option for those with advanced NSCLC. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who have specific mutations in EGFR or HER2 genes. Participants must have a life expectancy of at least 12 weeks, measurable disease by scans, and adequate organ function. They should have progressed after prior therapy but can't join if they've had certain recent treatments, unresolved toxicities from past cancer treatment, HIV/Hepatitis B/C infection, brain metastases requiring treatment, or serious heart issues.

Inclusion Criteria

I have a tumor that can be measured and has not been biopsied or treated with radiation.

I have recent or available tumor tissue samples for testing.

My liver is working well, according to recent tests.

Exclusion Criteria

I have side effects from cancer treatment, but they are not severe except for hair loss or skin color changes.

I have not had brain cancer or cancer spread to my brain that needed treatment.

I have had spinal cord compression or brain tumors, but with certain exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Doses of BAY2927088 will be increased in a stepwise fashion up to the maximum tolerated dose (MTD) or maximum administered dose (MAD).

3-week cycles

Up to 5 visits per cycle

Backfill

Test the doses of BAY2927088 that are considered safe in the escalation part by giving it to more participants.

3-week cycles

Up to 5 visits per cycle

Dose Expansion

Determine the dose of BAY2927088 to be tested in further studies.

3-week cycles

Up to 5 visits per cycle

Extension

Determine whether the selected dose of BAY2927088 from the expansion part works well.

3-week cycles

Up to 5 visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BAY2927088

Trial Overview

The study tests different formulations of BAY2927088 to find the safest dose that affects the body positively and determine how it's processed by the body. It involves three parts: increasing doses until safe limits are found (Dose Escalation), confirming these findings (Backfill), and giving an appropriate dose based on earlier results (Dose Expansion). Patients take the drug daily in cycles lasting three weeks each.

How Is the Trial Designed?

Group I: Extension part Experimental Treatment 2 Interventions

Initiation of the Extension part will depend on the benefit-risk profile observed during Dose Expansion. Additionally, enrollment may be prematurely terminated based on emerging data at the discretion of the Sponsor.

Group II: Dose expansion Experimental Treatment 2 Interventions

Eight independent groups (group A, B1, B2, C, D, E, F, G) are planned. Dose Expansion may start at a dose level that has been evaluated in Escalation/Backfill in at least 9 participants and considered safe or at any other dose levels that are below the highest dose level that is considered safe.

Group III: Dose escalation Experimental Treatment 3 Interventions

Doses of BAY2927088 will be increased in a stepwise fashion up to the MTD or MAD.

Group IV: Backfill Experimental Treatment 3 Interventions

Dose Escalation and Backfill run concurrently

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

BRAF mutations are found in about 4% of non-small cell lung cancer (NSCLC) cases, and targeted treatments like the combination of dabrafenib and trametinib have shown efficacy specifically for patients with the V600E mutation, highlighting the importance of genetic testing in treatment planning.

Despite the effectiveness of targeted therapies for V600E mutations, nearly half of BRAF-mutated NSCLC patients do not have access to these treatments, indicating a need for ongoing research into new therapeutic strategies for both V600E and non-V600E BRAF mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How far we have come targeting BRAF-mutant non-small cell lung cancer (NSCLC). Tabbò, F., Pisano, C., Mazieres, J., et al.[2022]

Lung cancer remains a critical global health issue, with over 1.6 million new diagnoses annually, but significant advancements in prevention and treatment are being made, particularly in immunotherapy and targeted therapies.

Recent breakthroughs in understanding molecular mechanisms and resistance to therapies have led to regulatory approvals of new treatments that enhance survival and quality of life for patients with advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scientific Advances in Lung Cancer 2015. Tsao, AS., Scagliotti, GV., Bunn, PA., et al.[2022]

In a meta-analysis of 51 studies with 12,600 participants, the development of immune-related adverse events (irAEs) was linked to improved overall survival (OS) and objective response rate (ORR) in advanced non-small cell lung cancer (NSCLC).

Checkpoint inhibitor pneumonitis (CIP) did not significantly affect overall survival but was associated with a better treatment response, indicating that while CIP may not be detrimental to survival, it can enhance the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Immune-Related Adverse Events and Pneumonitis on Prognosis in Advanced Non-Small Cell Lung Cancer: A Comprehensive Systematic Review and Meta-analysis. Li, Y., Zhang, Y., Jia, X., et al.[2022]

Dabrafenib, a BRAF inhibitor, shows significant effectiveness as a single-agent treatment for patients with advanced non-small cell lung cancer that has the BRAF V600E mutation, indicating its potential as a targeted therapy.

Combining dabrafenib with a MEK inhibitor may enhance treatment efficacy, suggesting that a combination therapy approach could be more beneficial for these patients than using dabrafenib alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib Active in Rare NSCLC Subtype. [2017]

In the LUX-Lung 7 trial, afatinib improved progression-free survival compared to gefitinib in patients with non-small cell lung cancer, with 160 patients receiving afatinib and 159 receiving gefitinib.

Dose adjustments for afatinib reduced the incidence and severity of treatment-related adverse events without significantly affecting progression-free survival, allowing patients to potentially continue treatment longer even after initial signs of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line afatinib vs gefitinib for patients with EGFR mutation-positive NSCLC (LUX-Lung 7): impact of afatinib dose adjustment and analysis of mode of initial progression for patients who continued treatment beyond progression. Schuler, M., Tan, EH., O'Byrne, K., et al.[2020]

In a systematic review of 21 trials involving 3176 patients with EGFR+ non-small cell lung cancer (NSCLC), the mean incidence of bone metastases at diagnosis was found to be 42%, highlighting a significant concern for this patient population.

Despite the high incidence of bone metastases, there is a notable lack of screening and reporting on bone-related outcomes and skeletal-related events (SREs) in clinical trials, indicating a gap in the management of these complications in EGFR+ NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of Incidence and Outcome of Bone Metastases in Clinical Trials Enrolling Patients with Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma-A Systematic Review. Brouns, A., Dursun, S., Bootsma, G., et al.[2023]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

In a prospective study involving 55 patients with resectable non-small cell lung cancer (NSCLC), early onset immune-related adverse events (irAEs) like rash and thyroid dysfunction were associated with better clinical outcomes, including major and complete pathological responses after neoadjuvant treatment.

Specifically, 85.7% of patients with rash or pruritus achieved a major pathological response, indicating that these easily identifiable irAEs could serve as useful indicators for predicting treatment efficacy in NSCLC patients undergoing neoadjuvant chemo-immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of early immune-related adverse events with treatment efficacy of neoadjuvant Toripalimab in resectable advanced non-small cell lung cancer. Tao, Y., Li, X., Liu, B., et al.[2023]

In a review of 12 phase III randomized controlled trials involving 7470 patients, sunitinib was found to be associated with a 1.2% incidence of fatal adverse events (FAEs), significantly increasing the risk compared to control groups (relative risk of 2.34).

The most common cause of FAEs linked to sunitinib was hemorrhage, indicating a critical safety concern for patients undergoing treatment with this tyrosine kinase inhibitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of fatal adverse events in cancer patients treated with sunitinib. Zhao, B., Zhao, H., Zhao, J.[2019]

The combination treatment of zoledronic acid, cisplatin, and docetaxel was well-tolerated in 35 patients with non-small cell lung cancer and bone metastases, with no severe renal toxicity observed.

The treatment showed a modest objective response rate of 29% and improved pain scores in 77% of patients after six weeks, indicating some efficacy in managing symptoms and disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of zoledronic acid plus cisplatin-docetaxel as first-line treatment for advanced non-small cell lung cancer with bone metastases. Yoh, K., Kubota, K., Ohmatsu, H., et al.[2018]

Recent approvals of novel therapies, such as antiangiogenics (nindetanib and ramucirumab) and immunotherapies (nivolumab, pembrolizumab, and atezolizumab), provide new treatment options for patients with advanced non-small cell lung cancer (NSCLC) who have limited benefits from traditional therapies.

The paper emphasizes the need to understand how these new therapies are integrated into clinical practice and proposes a shared algorithm for second-line treatment in advanced NSCLC, highlighting the importance of optimizing patient care with these emerging options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line Treatment of Advanced Non-small Cell Lung Cancer Non-oncogene Addicted: New Treatment Algorithm in the Era of Novel Immunotherapy. Gridelli, C., Ascierto, PA., Grossi, F., et al.[2021]

A study of 227 lung cancer patients revealed significant differences in the incidence of treatment-related adverse events (AEs) among various PD-1 inhibitors, with camrelizumab showing the highest rate of all-grade AEs at 62.96%, while toripalimab had the lowest at 9.52%.

The most common AEs varied by drug, with camrelizumab associated with capillary hemangioma and abnormal liver function, while nivolumab and pembrolizumab were linked to pneumonitis, indicating the need for tailored monitoring strategies based on the specific PD-1 inhibitor used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of different PD-1 inhibitors in lung cancer patients: a real-world study. Zheng, X., Tao, G., Sun, S., et al.[2022]

In the phase 3 LUX-Lung 8 study, afatinib significantly improved progression-free survival and overall survival compared to erlotinib in patients with relapsed squamous cell carcinoma of the lung, demonstrating its efficacy as a treatment option.

A specific case of a 53-year-old patient showed that afatinib led to a progression-free period of 14.7 months and an overall survival of 17.7 months, with tolerability-guided dose adjustments helping manage side effects, emphasizing the importance of personalized treatment strategies based on genetic profiling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy of afatinib in a patient with squamous cell carcinoma of the lung and multiple ERBB family aberrations: afatinib in ERBB+ lung squamous cell carcinoma. Jian, H., Han, Y., Yu, Y., et al.[2020]

In a phase III study involving 345 patients with advanced lung adenocarcinoma and EGFR mutations, afatinib significantly improved progression-free survival (PFS) to 11.1 months compared to 6.9 months for standard chemotherapy, indicating its efficacy as a treatment option.

Patients treated with afatinib experienced fewer severe side effects and reported better control of symptoms like cough and pain, suggesting that afatinib not only prolongs survival but also enhances quality of life compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. Sequist, LV., Yang, JC., Yamamoto, N., et al.[2023]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8504

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 ...

2.

iaslc.org

iaslc.org/iaslc-news/press-release/breakthrough-therapy-bay-2927088-demonstrates-rapid-substantial-and

Breakthrough Therapy BAY 2927088 Demonstrates 'Rapid ...

Treatment with BAY 2927088 led to rapid, substantial, and durable responses in patients with heavily pretreated HER2-mutant non-small cell lung cancer (NSCLC).

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06452277

NCT06452277 | A Study to Learn More About How Well ...

The study treatment, BAY 2927088, is expected to block the mutated HER2 protein which may stop the spread of NSCLC. The main purpose of this study is to learn ...

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(23)03246-5/fulltext

1320MO Early evidence of efficacy in patients (pts) with ...

In an early phase I analysis of pts with EGFR- or HER2-mutant NSCLC, BAY 2927088 demonstrated a manageable safety profile up to 60 mg daily. In pts with HER2 ...

5.

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) ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05099172

NCT05099172 | First in Human Study of BAY2927088 ...

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