Zongertinib for Solid Tumors

Recruiting at 98 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

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study for people with advanced cancer for whom previous treatment was not successful. Adults aged 18 and over with advanced cancer with HER2 alterations can join the study. The purpose of this study is to find out whether a medicine called zongertinib helps people with advanced cancers with HER2 alterations. HER2 alterations can cause cancer. Zongertinib inhibits HER2. Participants are put into 13 groups based on the type of advanced cancer and the type of HER2 alterations they have. All participants take one dose of zongertinib each day. Participants can continue the treatment as long as they benefit from it and can tolerate it. Participants visit the study site regularly. During many of the visits, the doctors check the size of the tumour and whether it has spread to other parts of the body. During all the visits, the doctors check participants' health and take note of any unwanted effects.

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.

What data supports the effectiveness of the drug Zongertinib for solid tumors?

The drug BI 1810631, which is part of Zongertinib, has shown preliminary effectiveness in treating solid tumors with HER2 abnormalities by specifically targeting and binding to HER2 receptors. Additionally, similar drugs like poziotinib and neratinib, which also target HER2, have demonstrated promising results in treating HER2-positive cancers, suggesting potential effectiveness for Zongertinib. ^{1 2 3 4 5}

What makes the drug Zongertinib unique for treating solid tumors?

Zongertinib is unique because it specifically targets HER2 receptors, including certain mutations, without affecting EGFR signaling, which may reduce side effects compared to other treatments that target multiple receptors. ^{1 2 3 6 7}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. 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]

3. England 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. [2022]

4. England 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. [2020]

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

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

6. United States 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. [2021]

7. England 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. [2018]