Zongertinib for Lung Cancer

Recruiting in Palo Alto (17 mi)

+179 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Boehringer Ingelheim

Must not be taking: Restricted medications

Disqualifiers: Other malignancies, Severe illness, Cardiovascular, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

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.

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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.

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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

Trial 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

Participant Groups

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.

Group I: Experimental treatment arm Experimental Treatment 1 Intervention

zongertinib only

Group II: Comparator arm Active Control 4 Interventions

pembrolizumab plus platinum-pemetrexed chemotherapy

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Oncology Hematology Associates Springfield, MO

Mohtaseb Cancer Center and Blood Disorders, LLC Bullhead City, AZ

Huntsman Cancer Institute Salt Lake City, UT

Clearview Cancer Institute Huntsville, AL

More Trial Locations

Who Is Running the Clinical Trial?

Boehringer Ingelheim Lead Sponsor

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] Label="PURPOSE">Targeted therapies against non-small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with HER2 exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study.

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

Targeting HER2 May Overtake Chemo, Immunotherapy in NSCLC. [2022] Results from phase II trials of two HER2-targeting agents, the antibody-drug conjugate trastuzumab deruxtecan and the HER2-targeting tyrosine kinase inhibitor poziotinib, indicate promising efficacy that could lead to new standards of care for HER2-mutant non-small cell lung cancer.

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] Label="Background" NlmCategory="UNASSIGNED">HER2-targeted therapy provides survival benefits to HER2-mutant non-small cell lung cancer (NSCLC). A better understanding of the clinical and genomic characterization of treatment-naïve HER2-positive NSCLC, as well as the efficacy of and resistance to HER2-targeted therapy in HER2-altered NSCLC, could promote further improvement of HER2 targeted therapy.

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

Targeting the EGF receptor family in non-small cell lung cancer-increased complexity and future perspectives. [2023] Lung cancer remains the leading cause of cancer-associated mortality worldwide, but with the emergence of oncogene targeted therapies, treatment options have tremendously improved. Owing to their biological relevance, members of the ERBB receptor family, including the EGF receptor (EGFR), HER2, HER3 and HER4, are among the best studied oncogenic drivers. Activating EGFR mutations are frequently observed in non-small cell lung cancer (NSCLC), and small molecule tyrosine kinase inhibitors (TKIs) are the established first line treatment option for patients whose tumors bear "typical/classical" EGFR mutations (exon 19 deletions, L858R point mutations). Additionally, new TKIs are rapidly evolving with better efficacy to overcome primary and secondary treatment resistance (e.g., that due to T790M or C797S resistance mutations). Some atypical EGFR mutations, such as the most frequent exon 20 insertions, exhibit relative resistance to earlier generation TKIs through steric hindrance. In this subgroup, newer TKIs, such as mobocertinib and the bi-specific antibody amivantamab have recently been approved, whereas less frequent atypical EGFR mutations remain understudied. In contrast to EGFR, HER2 has long remained a challenging target, but better structural understanding has led to the development of newer generations of TKIs. The recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic breakthrough. HER3 and HER4 also exert oncogenic potential, and targeted treatment approaches are being developed, particularly for HER3. Overall, strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace; therefore, this review summarizes current treatment standards and discusses the outlook for future developments.

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] Non-small-cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) exon 20 mutant occurs in 3% of NSCLCs. Targeted agents for this population remain an unmet need. In this analysis, we pooled-analyzed the efficacy and safety of poziotinib, a novel tyrosine kinase inhibitor, in HER2 exon 20 mutant NSCLC.

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] To provide an overview of the clinical development of ZD1839 and other epidermal growth factor receptor (EGFR) inhibitors in the treatment of advanced non-small cell lung cancer (NSCLC).

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

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. [2018] To study e the therapeutic and adverse effects of ZD1839 in treating non-small-cell lung cancer (NSCLC).

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] The epidermal growth factor receptor is overexpressed in a majority of non-small cell lung cancers and has been associated with a poor prognosis. Preclinical studies have shown that ZD1839, an oral anilinoquinazoline, targets the epidermal growth factor receptor-associated tyrosine kinase, reversibly inhibiting critical downstream signaling and resulting in cancer cell growth arrest. Potent antitumor effects have been observed in human lung tumor xenograft models. Preclinical studies have shown additive to synergistic effects when ZD1839 is combined with radiation or chemotherapy in colon, head and neck, and non-small cell lung cancers. Phase I clinical trials have shown modest dose-related toxicity, and antitumor activity has been reported in a variety of malignancies including lung cancer. Future studies will certainly combine ZD1839 with chemotherapy or radiation. ZD1839 also may be effective as a chemoprevention agent because premalignant lesions often overexpress epidermal growth factor receptor.

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] Poziotinib (HM781-36B) is an irreversible pan-HER tyrosine kinase inhibitor which targets EGFR, HER2, and HER4. This prospective, multicenter, open-label, phase I/II study determined the maximum tolerated dose (MTD) and evaluated the safety and efficacy of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer (GC).