Zongertinib for Solid Tumors

Recruiting at 116 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Boehringer Ingelheim

Must not be taking: Restricted medications

Disqualifiers: HER2 mutant NSCLC, recent malignancies, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 37 months

430 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine called zongertinib, a HER-2 inhibitor, to determine its effectiveness for people with advanced cancers involving changes in the HER2 protein, which can promote cancer growth. Eligible participants have advanced cancer unresponsive to previous treatments and HER2 changes in their cancer. Participants are divided into 13 groups based on cancer type and HER2 changes and will take zongertinib daily. Doctors will regularly monitor tumor size and overall health. This trial excludes those with a specific type of lung cancer unless they have additional HER2 changes. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 patients who need to continue taking medications that might interfere with the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that zongertinib is generally safe and well-tolerated. In earlier studies, patients handled the treatment well. While some side effects occurred, they were usually mild. Zongertinib targets a protein called HER2, which can promote cancer cell growth, without affecting another protein, EGFR. This selectivity helps minimize unwanted side effects. Overall, the treatment appears well-tolerated in individuals with tumors that have HER2 alterations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Zongertinib is unique because it targets solid tumors with a novel mechanism of action. Unlike traditional treatments such as chemotherapy, which often attack both cancerous and healthy cells, Zongertinib specifically aims at molecular pathways that are overactive in tumor cells. This targeted approach has the potential to minimize side effects and improve the precision of cancer treatment, making it an exciting development in the fight against solid tumors. Researchers are particularly enthusiastic about its potential to offer more effective and personalized treatment options.

What evidence suggests that zongertinib might be an effective treatment for advanced cancer with HER2 alterations?

Research has shown that zongertinib, a drug targeting the HER2 protein, may help treat cancers with changes in this protein. In earlier studies, patients with non-small cell lung cancer (NSCLC) who took zongertinib had their cancer remain stable for an average of 17.2 months. Another study found that in cases with altered HER2 protein, the cancer stayed stable for about 6.8 months on average. Zongertinib blocks the HER2 protein, potentially stopping cancer cells from growing and spreading. These results suggest that zongertinib might effectively manage advanced cancers with HER2 changes. Participants in this trial will receive zongertinib to further evaluate its effectiveness in treating solid tumors with HER2 alterations. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults over 18 with advanced cancers that have HER2 alterations, which can cause cancer growth. Participants must have tried all other treatments without success or be unsuitable for existing options. They need to provide a tissue sample to confirm HER2 status unless an exception is granted.

Inclusion Criteria

My cancer shows high levels of HER2.

I have signed and understand the consent form for this trial.

My cancer has a known HER2 mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral zongertinib and are monitored for tumour size and health effects

Up to 37 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zongertinib

Trial Overview The study tests Zongertinib's effectiveness on various advanced cancers with HER2 alterations. Patients are divided into 10 groups based on their cancer type and specific HER2 changes, and they take Zongertinib as long as it helps them and they can handle it.

How Is the Trial Designed?

Group I: Zongertinib treatment Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

S-222611, a reversible inhibitor of EGFR, HER2, and HER4, was well tolerated in a Phase 1 study with 33 patients, showing mild side effects like diarrhea and rash, and did not reach a maximum tolerated dose (MTD).

The drug demonstrated significant antitumor activity, with responses in various solid tumors, including a complete response in a HER2-positive breast cancer patient, leading to a recommended Phase 2 dose of 800 mg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 dose-escalation study of S-222611, an oral reversible dual tyrosine kinase inhibitor of EGFR and HER2, in patients with solid tumours. Spicer, J., Baird, R., Suder, A., et al.[2018]

AZD8931, an oral inhibitor targeting EGFR, HER2, and HER3, was found to be safe and tolerable in a Phase I study involving 28 patients with advanced solid tumors, with a maximum tolerated dose established at 240 mg twice daily.

The most common side effects included skin reactions and diarrhea, and while 12 out of 21 evaluable patients had stable disease after 21 days of treatment, further long-term studies are necessary to confirm its effectiveness for chronic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, dose-finding study of AZD8931, an inhibitor of EGFR (erbB1), HER2 (erbB2) and HER3 (erbB3) signaling, in patients with advanced solid tumors. Tjulandin, S., Moiseyenko, V., Semiglazov, V., et al.[2021]

BI 1810631 is a promising oral treatment for patients with HER2 mutation-positive solid tumors, specifically targeting both wild-type and mutated HER2 receptors while sparing EGFR signaling, which may enhance safety.

The study aims to determine the maximum tolerated dose and preliminary efficacy of BI 1810631 in patients with advanced HER2 aberration-positive tumors, with a focus on those with non-small cell lung cancer who have previously undergone systemic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I, Open-Label, Dose Confirmation, Escalation, and Expansion Trial of BI 1810631 as Monotherapy in Patients With Advanced or Metastatic Solid Tumors With HER2 Aberrations. Heymach, J., Opdam, F., Barve, M., et al.[2023]

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]

In a Phase I/II study involving 91 patients, the combination of neratinib (240 mg/day) and vinorelbine (25 mg/m2) demonstrated promising antitumor activity in HER2-positive metastatic breast cancer, with an objective response rate of 41% in patients who had not previously received lapatinib.

The treatment was generally well-tolerated, with diarrhea (96%) and neutropenia (54%) being the most common side effects, but no unexpected toxic effects were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. Awada, A., Dirix, L., Manso Sanchez, L., et al.[2020]

In a Phase 1 study involving 21 Japanese patients with advanced solid tumors, neratinib was found to have a maximum-tolerated dose of 240 mg daily, with common side effects including diarrhea and fatigue.

The study showed that neratinib led to partial responses in 2 breast cancer patients and stable disease in several others, indicating its potential efficacy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study. Ito, Y., Suenaga, M., Hatake, K., et al.[2022]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40030100/

HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI ... In patients with NSCLC receiving zongertinib once daily, median progression-free survival was 17.2 months (95% CI, 8.3 to NR). Conclusion: ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01727

HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI ... In patients with NSCLC receiving zongertinib once daily, median progression-free survival was 17.2 months (95% CI, 8.3 to NR). Conclusion.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2503704

Zongertinib in Previously Treated HER2-Mutant Non–Small ... The median progression-free survival was 6.8 months (95% CI, 5.4 to not evaluable). In the exploratory cohort 3, a total of 6 patients with ...

4. aacrjournals.org aacrjournals.org/cancerdiscovery/article/15/1/119/750858/Zongertinib-BI-1810631-an-Irreversible-HER2-TKI

Zongertinib (BI 1810631), an Irreversible HER2 TKI, Spares ... Zongertinib dose-dependently inhibited growth of tumors, delaying tumor growth at 2.5 mg/kg twice a day and 5 mg/kg every day and shrinking ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424010633

MA12.10 Zongertinib (BI 1810631) For HER2-Positive ... The median duration of response was 12.7 months. Median progression-free survival (PFS) was 8.0 months and 8.3 months with zongertinib BID and QD, respectively.

6. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/payor/vital-perspectives/oncology/zongertinib-clinical-overview

Zongertinib Clinical Overview | Vital Perspectives Beamion LUNG-1: Phase Ia/b trial of HER2 tyrosine kinase inhibitor zongertinib (BI 1810631) in patients with HER2 aberration-positive solid tumors.