BAY2927088 for Non-Small Cell Lung Cancer

(SOHO-02 Trial)

Recruiting at 340 trial locations

Overseen By Bayer Clinical Trials Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bayer

Must be taking: Platinum-based chemotherapy

Must not be taking: Chronic systemic corticosteroids

Disqualifiers: Prior malignancy, Peripheral neuropathy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 2 years

278 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are looking for a better way to treat people who have advanced non-small cell lung cancer (NSCLC) with specific genetic changes called human epidermal growth factor receptor 2 (HER2) mutations. Advanced NSCLC is a group of lung cancers that have spread to nearby tissues or to other parts of the body or that are unlikely to be cured or controlled with currently available treatments. HER2 is a protein that helps cells to grow and divide. A damage (also called mutation) to the building plans (genes) for this protein in cancer cells leads to a production of abnormal HER2 and therefore abnormal cell growth and division. 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 how well BAY 2927088 works and how safe it is compared with standard treatment, in participants who have advanced NSCLC with specific genetic changes called HER2 mutations. The study participants will receive one of the study treatments: * BAY 2927088 twice every day as a tablet by mouth, or * Standard treatment in cycles of 21 days via infusion ("drip") into the vein. The treatment will continue for as long as participants benefit from it without any severe side effects or until they or their doctor decide to stop the treatment. During the study, the doctors and their study team will: * take imaging scans, including CT, PET, MRI, and X-rays, of different parts of the body to study the spread of cancer * check the overall health of the participants by performing tests such as blood and urine tests, and checking * heart health using an electrocardiogram (ECG) * perform pregnancy tests for women * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are unable to stop chronic systemic corticosteroids. Other medications may be allowed, but it's best to discuss your specific situation with the study team.

What data supports the effectiveness of the drug BAY 2927088 for non-small cell lung cancer?

The research suggests that early phase trials of targeted therapies in lung cancer, like BAY 2927088, often show promising results that are consistent with later, larger trials. This indicates that early positive outcomes might reliably predict effectiveness in broader use. ^{1 2 3 4 5}

What makes the drug BAY2927088 unique for treating non-small cell lung cancer?

BAY2927088 is unique because it targets specific genetic mutations in non-small cell lung cancer, potentially offering a tailored treatment option for patients with these mutations, unlike standard treatments that may not address these specific genetic factors. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has spread and has specific HER2 gene mutations. Participants must be able to take oral medication and undergo regular health checks, imaging scans, and possibly pregnancy tests.

Inclusion Criteria

I haven't had systemic therapy for advanced cancer or specific HER2 treatments.

My cancer has a specific HER2 mutation confirmed by a certified lab test.

I am at least 18 years old or the legal age of consent in my country.

Exclusion Criteria

I cannot stop taking my long-term steroids but don't use them heavily for asthma or local injections.

I have moderate to severe nerve damage in my hands or feet.

My tumor has a genetic change treatable with approved drugs, except for HER2 changes in the TKD.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BAY 2927088 twice daily as a tablet by mouth or standard treatment in 21-day cycles via infusion until disease progression or unacceptable toxicity

Up to approximately 2 years

Regular visits for imaging scans and health assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 4 years

Treatment Details

Interventions

• BAY 2927088

Trial Overview The effectiveness and safety of BAY 2927088, a tablet taken twice daily aimed at blocking mutated HER2 proteins in NSCLC patients, are being compared with standard chemotherapy treatments administered via infusion every 21 days.

Participant Groups

Group I: BAY2927088 Experimental Treatment 1 Intervention

Participants will receive BAY2927088 20 mg BID until disease progression per RECIST v1.1, unacceptable toxicity, or until any other withdrawal criteria.

Group II: Standard of care (SoC) Active Control 4 Interventions

Participants will receive SoC (pembrolizumab in combination with platinum-based chemotherapy, in 21-day cycles per the approved labels) until disease progression per RECIST v1.1, unacceptable toxicity, or until any other withdrawal criteria.

BAY 2927088 is already approved in United States for the following indications:

Approved in United States as BAY 2927088 for:

• Non-small cell lung cancer (NSCLC) with HER2 mutations

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

The maximum tolerated dose (MTD) of lenvatinib when combined with carboplatin and paclitaxel for treating advanced non-small-cell lung cancer (NSCLC) is established at 4 mg taken twice daily, showing manageable side effects.

The treatment regimen resulted in a response rate of 68% and a median progression-free survival of 9.0 months, indicating promising antitumor activity in chemotherapy-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer. Nishio, M., Horai, T., Horiike, A., et al.[2021]

Efficacy outcomes from early phase trials of targeted therapies for oncogene-driven lung cancer, such as objective response rate (ORR) and progression-free survival (PFS), have historically been consistent with those from later phase trials, suggesting reliability in early trial results.

This consistency implies that early phase trials can provide valuable insights for regulatory approvals and the design of future clinical trials, potentially streamlining the development of new lung cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of targeted therapies for oncogene-driven lung cancer in early single-arm versus late phase randomized clinical trials: A comparative analysis. Tan, AC., Tan, SH., Zhou, S., et al.[2022]

The phase III CHOICE-01 trial in China demonstrated that the PD-1 inhibitor toripalimab combined with chemotherapy significantly improves progression-free survival in patients with untreated non-small cell lung cancer that lacks actionable mutations.

These results support the use of combination chemo-immunotherapy as a new standard treatment approach for this patient population, moving away from chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing Toripalimab in NSCLC. [2022]

CT-guided core-needle biopsy is a safe and effective method for obtaining tissue samples from patients with advanced non-small-cell lung cancer (NSCLC) for EGFR gene mutation analysis, with no life-threatening complications reported in the study of 17 patients.

In this study, 70.6% of patients had EGFR gene mutations, and those with mutations showed a significantly higher response rate (91.7%) to the EGFR inhibitor gefitinib compared to nonmutants, who had a 0% response rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computed tomography-guided core-needle biopsy specimens demonstrate epidermal growth factor receptor mutations in patients with non-small-cell lung cancer. Chen, CM., Chang, JW., Cheung, YC., et al.[2018]

In lung cancer cell lines with FGFR1 amplification, the FGFR inhibitors AZD4547 and BAY116387 showed significant antitumor activity, particularly in sensitive cell lines like H1581 and DMS114.

Acquired resistance to these FGFR inhibitors was linked to the overexpression and activation of the Met receptor, which can bypass FGFR signaling; combining FGFR inhibitors with Met inhibitors like crizotinib may enhance treatment efficacy against resistant lung cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy. Kim, SM., Kim, H., Yun, MR., 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 the FLAURA China study involving 136 patients with EGFR mutation-positive advanced non-small-cell lung cancer, first-line treatment with osimertinib significantly improved progression-free survival (PFS) by 8 months compared to comparator EGFR TKIs, with median PFS of 17.8 months versus 9.8 months.

Osimertinib also showed a trend towards improved overall survival (OS) with a median of 33.1 months compared to 25.7 months for the comparator group, while the safety profile was consistent with previous findings, with no new safety signals identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. Cheng, Y., He, Y., Li, W., et al.[2022]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of targeted therapies for oncogene-driven lung cancer in early single-arm versus late phase randomized clinical trials: A comparative analysis. [2022]

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

Assessing Toripalimab in NSCLC. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Computed tomography-guided core-needle biopsy specimens demonstrate epidermal growth factor receptor mutations in patients with non-small-cell lung cancer. [2018]

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

Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. France pubmed.ncbi.nlm.nih.gov

Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. [2022]

8. 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]

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

Scientific Advances in Lung Cancer 2015. [2022]

10. 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]