Zongertinib for Lung Cancer

Recruiting at 186 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: Restricted medications

Disqualifiers: Other malignancies, Severe illness, Cardiovascular, 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

Compensation: Varies

Number of Visits: 3

Duration: up to 70 months

270 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is open to adults 18 years and older with advanced or metastatic non-small cell lung cancer. People can join the study if they have tumours with HER2 mutations and have not yet received any systemic therapy including chemotherapy for advanced or metastatic lung cancer. The purpose of this study is to find out whether a medicine called zongertinib (BI 1810631) can slow down the worsening of advanced non-small cell lung cancer better than the standard treatment available. Zongertinib may slow cancer cell growth by inhibiting HER2. This would prolong cancer re-occurrence and increase survival. Current standard treatment is pembrolizumab plus platinum-pemetrexed chemotherapy. Participants are put into 2 groups by chance. One group receives zongertinib at regular times throughout the study and the other group receives infusions of pembrolizumab, pemetrexed and cisplatin or carboplatin (pembrolizumab plus platinum-pemetrexed chemotherapy) into a vein. Participants may be in the study up to a maximum of 70 months. During this time, they visit the study site about every 3 weeks for study procedures. The doctors regularly check the size of the tumour with a CT or MRI scan, at the beginning of the study and every 6 weeks. After 18 months they check the tumour size every 12 weeks. Doctors regularly check whether the cancer has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects. The time it takes for the cancer to worsen is compared between the 2 groups to see whether the treatment works. The participants also fill in questionnaires about their symptoms and quality of life.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those who need to continue taking medications that might interfere with the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Zongertinib for lung cancer?

Research on similar drugs like poziotinib, which targets the same HER2 mutations in lung cancer, shows promising results in improving treatment outcomes for patients with these specific genetic changes. ^{1 2 3 4 5}

How is the drug Zongertinib different from other lung cancer treatments?

Zongertinib is unique because it specifically targets HER-2, a protein that can promote the growth of cancer cells, making it potentially effective for lung cancers with HER-2 mutations. This is different from other treatments that may target different proteins or pathways. ^{1 6 7 8 9}

Eligibility Criteria

Adults over 18 with advanced non-small cell lung cancer and HER2 mutations, who haven't had systemic therapy for their condition. They must have a tumor that can be measured by scans and be able to receive platinum-based chemotherapy with pembrolizumab.

Inclusion Criteria

More requirements need to be met to join the study.

I have signed the consent form for this trial following all required guidelines.

I am 18 years old or older, or meet my country's legal age for medical consent.

Exclusion Criteria

My tumor has changes that can be treated with approved drugs.

Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the safety and efficacy of the test drug

Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either zongertinib or pembrolizumab plus platinum-pemetrexed chemotherapy. Tumor size is checked regularly with CT or MRI scans.

up to 70 months

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Tumor size is checked every 12 weeks after 18 months.

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Zongertinib

Trial Overview The trial is testing if Zongertinib (BI 1810631) is more effective than the standard treatment of pembrolizumab plus platinum-pemetrexed chemotherapy in slowing down advanced lung cancer progression.

Participant Groups

Group I: Experimental treatment arm Experimental Treatment 1 Intervention

zongertinib only

Group II: Comparator arm Active Control 4 Interventions

pembrolizumab plus platinum-pemetrexed chemotherapy

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

In a phase II study involving 30 patients with advanced HER2 exon 20 mutant non-small-cell lung cancer (NSCLC), poziotinib demonstrated a confirmed objective response rate of 27%, indicating its potential effectiveness as a targeted therapy.

The treatment was associated with a median overall survival of 15 months and a median progression-free survival of 5.5 months, although it also had notable side effects, including skin rash and diarrhea, with one possible treatment-related death from pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poziotinib for Patients With HER2 Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial. Elamin, YY., Robichaux, JP., Carter, BW., et al.[2023]

Phase II trials of trastuzumab deruxtecan and poziotinib, both targeting HER2, show promising efficacy in treating HER2-mutant non-small cell lung cancer.

These results suggest that these agents could establish new standards of care for patients with this specific type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting HER2 May Overtake Chemo, Immunotherapy in NSCLC. [2022]

In a study of 176 treatment-naïve patients with HER2 alterations in non-small cell lung cancer (NSCLC), it was found that 64.8% had HER2 mutations with or without amplification, while 35.2% had only HER2 amplification, indicating distinct molecular characteristics between these groups.

Among 21 patients treated with HER2-targeted therapies, pyrotinib showed a longer median progression-free survival (5.9 months) compared to afatinib (4.0 months), suggesting that pyrotinib may be a more effective treatment option for HER2-altered NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic landscape and efficacy of HER2-targeted therapy in patients with HER2-mutant non-small cell lung cancer. Han, Y., Xiong, Y., Lu, T., et al.[2023]

Activating mutations in the EGFR gene are common in non-small cell lung cancer (NSCLC), and first-line treatment with small molecule tyrosine kinase inhibitors (TKIs) has significantly improved outcomes for patients with these mutations.

Newer TKIs and therapies, such as mobocertinib and trastuzumab-deruxtecan, have been developed to target both common and atypical EGFR mutations, as well as HER2 mutations, marking important advancements in treatment options for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the EGF receptor family in non-small cell lung cancer-increased complexity and future perspectives. Boch, T., Köhler, J., Janning, M., et al.[2023]

Poziotinib, a novel tyrosine kinase inhibitor, shows moderate efficacy in treating HER2 exon 20 mutant non-small-cell lung cancer (NSCLC), with an objective response rate of 27% and a disease control rate of 72% based on a pooled analysis of three clinical trials involving 126 patients.

The treatment has a manageable safety profile, with the most common severe side effects being skin rash (36%), diarrhea (23%), and oral mucositis (13%), indicating that while effective, monitoring for these adverse events is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials. Wang, BC., Kuang, BH., Liu, XX., et al.[2022]

ZD1839, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated effectiveness in treating advanced non-small cell lung cancer (NSCLC), showing improvements in symptoms and quality of life in two large phase II trials.

The ongoing research into ZD1839 and other EGFR inhibitors suggests they will play a significant role in NSCLC treatment, highlighting the need for healthcare professionals, especially nurses, to be informed about these emerging therapies for effective patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of clinical trials with epidermal growth factor receptor inhibitors in advanced non-small cell lung cancer. Thomas, M.[2019]

In a study of 32 patients with non-small-cell lung cancer (NSCLC) treated with ZD1839 for over 90 days, the drug achieved a disease control rate of 56.25%, with 18.75% experiencing partial remission.

ZD1839 was associated with manageable side effects, including acneiform rash (31.25%) and diarrhea (18.75%), but notably did not cause interstitial lung disease, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. Zhang, L.[2018]

ZD1839 effectively targets the epidermal growth factor receptor (EGFR) in non-small cell lung cancers, leading to cancer cell growth arrest and showing potent antitumor effects in preclinical models.

Clinical trials indicate that ZD1839 has manageable toxicity and demonstrates antitumor activity across various cancers, suggesting its potential for combination therapies with chemotherapy or radiation, as well as its use in chemoprevention for premalignant lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer. Raben, D., Helfrich, BA., Chan, D., et al.[2019]

The maximum tolerated dose (MTD) of poziotinib when combined with paclitaxel and trastuzumab for treating HER2-positive advanced gastric cancer was determined to be 8 mg/day, with manageable toxicity observed in the study.

In a cohort of 44 patients, the treatment combination showed promising efficacy, with a 21.9% objective response rate and median progression-free survival of 13 weeks, indicating potential benefits for patients previously treated with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer. Kim, TY., Han, HS., Lee, KW., et al.[2023]

References

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

Poziotinib for Patients With HER2 Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial. [2023]

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

Targeting HER2 May Overtake Chemo, Immunotherapy in NSCLC. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Genomic landscape and efficacy of HER2-targeted therapy in patients with HER2-mutant non-small cell lung cancer. [2023]

4. China pubmed.ncbi.nlm.nih.gov

Targeting the EGF receptor family in non-small cell lung cancer-increased complexity and future perspectives. [2023]

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

Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials. [2022]

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

Overview of clinical trials with epidermal growth factor receptor inhibitors in advanced non-small cell lung cancer. [2019]

7. China pubmed.ncbi.nlm.nih.gov

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. [2018]

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

ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer. [2023]