BAY2927088 for Non-Small Cell Lung Cancer

Recruiting at 139 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

370 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BAY2927088 for people with advanced lung cancer. The drug aims to block certain proteins that help cancer grow. Researchers want to find out how safe the drug is, the best dose to use, and how well it works in stopping cancer.

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.

What data supports the idea that BAY2927088 for Non-Small Cell Lung Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of BAY2927088 for Non-Small Cell Lung Cancer. Instead, it highlights other treatments like dabrafenib combined with a MEK inhibitor, which have shown significant activity in patients with certain mutations. Other drugs like afatinib have also been effective for different mutations in lung cancer, improving survival and treatment outcomes. However, there is no direct comparison or data available for BAY2927088 in the provided information. ^{1 2 3 4 5}

What data supports the effectiveness of the drug BAY2927088 for treating non-small cell lung cancer?

The research highlights the effectiveness of targeting specific mutations in non-small cell lung cancer, such as the BRAF V600E mutation, with drugs like dabrafenib and trametinib. These drugs have shown significant activity in clinical trials, suggesting that targeting similar pathways could be effective for other treatments like BAY2927088. ^{1 2 3 4 5}

What safety data is available for BAY2927088 in treating non-small cell lung cancer?

The provided research does not contain specific safety data for BAY2927088 or its variants (BAY 2927088, BAY-2927088) in the treatment of non-small cell lung cancer. The studies focus on PD-1/PD-L1 inhibitors and other treatments like sunitinib, but do not mention BAY2927088. Further specific studies or clinical trial results would be needed to determine the safety profile of BAY2927088. ^{6 7 8 9 10}

Is the drug BAY2927088 a promising treatment for Non-Small Cell Lung Cancer?

The information provided does not directly mention BAY2927088 or its effects on Non-Small Cell Lung Cancer. Therefore, we cannot determine if BAY2927088 is a promising treatment based on the given research articles. ^{5 11 12 13 14}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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 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]

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]

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]

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]

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 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]

References

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

Dabrafenib Active in Rare NSCLC Subtype. [2017]

2. Germany 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. [2020]

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

Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. [2023]

4. England 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. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

How far we have come targeting BRAF-mutant non-small cell lung cancer (NSCLC). [2022]

6. Germany 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. [2021]

7. United States 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. [2022]

8. Switzerland 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. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Risk of fatal adverse events in cancer patients treated with sunitinib. [2019]

10. China pubmed.ncbi.nlm.nih.gov

Adverse events of different PD-1 inhibitors in lung cancer patients: a real-world study. [2022]

11. Greece 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. [2018]

12. United Arab Emirates 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. [2021]

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

Scientific Advances in Lung Cancer 2015. [2022]

14. Switzerland 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. [2023]