BI 1810631 for Advanced Cancer

Recruiting at 100 trial locations

Overseen By Additional US locations available on demand. Please contact for options.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Systemic anti-cancer, Investigational drugs

Disqualifiers: Major surgery, Previous malignancies, others

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

Compensation: Varies

Number of Visits: Unknown

554 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, zongertinib (also known as BI 1810631, a HER2 exon 20 inhibitor), to determine its effectiveness for people with certain types of advanced cancer, particularly those with HER2 gene changes. The first part of the trial seeks to identify the highest dose patients can safely tolerate. Once determined, the second part will assess whether this dose can shrink tumors in individuals with non-small cell lung cancer (NSCLC) and a specific HER2 gene mutation. This trial may suit individuals whose advanced cancer treatments have failed and who have a confirmed HER2 gene change. Participants will take zongertinib tablets once or twice daily and will be monitored for health changes and side effects. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that patients who need to continue restricted medications or drugs that might interfere with the trial cannot participate. It's best to discuss your specific medications with the study team.

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

Research has shown that zongertinib, also known as BI 1810631, has generally been well-tolerated in past studies. In these trials, patients with tumors featuring changes in the HER2 gene experienced manageable side effects. While some side effects occurred, they were not severe enough to cause most participants to stop treatment.

Studies also found that zongertinib effectively shrinks tumors. It specifically targets the HER2 gene, which can promote cancer growth, without affecting the EGFR gene, which can cause side effects in some treatments.

Since this trial is in an early phase, the main goal is to determine the safest dose. Researchers continue to learn about possible side effects and closely monitor participants' health. If zongertinib proves effective and safe in this study, it could lead to better treatment options for people with advanced cancer. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for advanced cancer?

Most treatments for advanced cancer involve traditional chemotherapy or targeted therapies, which attack cancer cells but can also affect healthy cells and often come with significant side effects. BI 1810631 is different because it is designed to target cancer cells more precisely, potentially leading to fewer side effects. Researchers are excited about its novel mechanism of action that aims to interfere with the pathways specifically driving cancer growth, which might make it more effective and tolerable than current options. This targeted approach could offer a new avenue for patients who have limited treatment choices due to the advanced nature of their cancer.

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

Research has shown that zongertinib, also known as BI 1810631, might be promising for some advanced cancers targeting changes in the HER2 gene. In earlier studies with patients who have non-small cell lung cancer (NSCLC) and a HER2 mutation, those taking zongertinib once a day had a median progression-free survival of 17.2 months, meaning their disease did not worsen during that period. Another study found that 30% of patients experienced a reduction in tumor size across different doses and tumor types. These findings suggest that zongertinib could help shrink tumors in people with specific genetic changes in their cancer. This treatment remains under study in various cohorts of this trial, but early results are encouraging for those with HER2-related cancers. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with advanced cancers showing changes in the HER2 gene, who have not responded to previous treatments, can join this trial. They must be generally healthy, able to take tablets daily or twice a day, and willing to use effective birth control. People with certain blood counts and organ functions are eligible. Those with brain metastases that don't need immediate treatment may also qualify.

Inclusion Criteria

- Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator.

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

- Additional inclusion criteria for Phase Ib - Cohort 3 only:

Exclusion Criteria

My ductal carcinoma in situ has been treated successfully.

I had another cancer that was treated and is now considered cured.

I need to keep taking certain medications that may affect the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of zongertinib to determine the maximum tolerated dose

3 weeks (per cycle)

Regular health checks and monitoring

Dose Expansion

Participants receive the determined dose of zongertinib to assess tumor response

Up to 12 months

Regular health checks and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 1810631

Trial Overview The trial is testing BI 1810631's tolerable doses on various advanced cancers (Part 1) and its effectiveness in shrinking tumors in non-small cell lung cancer patients with specific HER2 mutations (Part 2). Participants will receive BI 1810631 orally as part of their ongoing treatment regimen while being monitored for health and tumor response.

How Is the Trial Designed?

Group I: Phase Ib - Dose expansion part: Cohort 8 Experimental Treatment 1 Intervention

Cohort only in the United States of America (USA)

Group II: Phase Ib - Dose expansion part: Cohort 7 Experimental Treatment 1 Intervention

Cohort only in Japan

Group III: Phase Ib - Dose expansion part: Cohort 6 Experimental Treatment 1 Intervention

Cohort only in the United States of America (USA)

Group IV: Phase Ib - Dose expansion part: Cohort 5 Experimental Treatment 1 Intervention

Group V: Phase Ib - Dose expansion part: Cohort 4 Experimental Treatment 1 Intervention

Group VI: Phase Ib - Dose expansion part: Cohort 3 Experimental Treatment 1 Intervention

Group VII: Phase Ib - Dose expansion part: Cohort 2 Experimental Treatment 1 Intervention

Group VIII: Phase Ib - Dose expansion part: Cohort 1 Experimental Treatment 1 Intervention

Group IX: Phase Ia - Dose escalation part Experimental Treatment 1 Intervention

Consecutive cohorts of patients treated with escalating doses of BI 1810631 monotherapy.

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

In the ZENITH20-C4 trial involving 80 treatment-naive patients with NSCLC and HER2 exon 20 insertions, poziotinib demonstrated a 39% objective response rate and a 73% disease control rate, indicating significant efficacy in this patient population.

The treatment was associated with manageable side effects, with the most common grade 3 adverse events being rash, stomatitis, and diarrhea, suggesting that poziotinib is a viable option for patients with these specific mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4). Cornelissen, R., Prelaj, A., Sun, S., 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]

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]

In a study of 194 patients with metastatic breast cancer, the pan-ErbB receptor inhibitor CI-1033 showed limited overall effectiveness, with only 1.5% response rates in lower dose arms and a slightly better 7.3% in the highest dose arm, indicating minimal clinical activity in heavily pretreated patients.

The highest dose (450 mg) led to a significant increase in severe side effects, with 80.4% of patients experiencing grade 3/4 adverse events, prompting early discontinuation of this regimen, while the 50 mg dose was better tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase II, dose-finding study of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in patients with pretreated metastatic breast cancer. Rixe, O., Franco, SX., Yardley, DA., et al.[2022]

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]

HER2 is a critical target in breast cancer treatment, as it is linked to tumor growth and poor prognosis in patients with high-risk HER2-positive breast cancer.

Prospective trials are being conducted to evaluate the effectiveness of anti-HER2 monoclonal antibody therapy, which may improve outcomes for patients with node-positive HER2-positive breast cancer, especially when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of adjuvant monoclonal antibody therapy for breast cancer: rationale and new studies. Perez, EA.[2019]

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]

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]

HER2-targeted therapies have significantly improved the prognosis for patients with HER2-positive advanced breast cancer, but resistance to these treatments is common, making ongoing research essential.

New strategies, including novel anti-HER2 antibodies, antibody-drug conjugates, and combination therapies targeting the tumor microenvironment and specific signaling pathways, are being developed to overcome resistance and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?pi. Mezni, E., Vicier, C., Guerin, M., et al.[2020]

Citations

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

Zongertinib in Previously Treated HER2-Mutant Non– ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11974636/

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. 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 ... The reported overall response rate (ORR) for KRASG12C varies between 28% and 53% (40–43) depending on the compound, dosing schedule, and ...

4. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-24-01727

HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI ... The confirmed investigator-assessed overall response rate (ORR) across all doses/tumors was 30% (95% CI, 23 to 40); median duration of response ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225000139

Very first real-world data on zongertinib use in non-small ... Zongertinib (BI 1,810,631) is a novel HER2-selective tyrosine kinase inhibitor. •. First real-world data on six consecutive patients with HER2-mutant NSCLC ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8514

Phase Ia/Ib trial of zongertinib (BI 1810631), a HER2- ... Zongertinib was well tolerated and demonstrated promising efficacy in pts with HER2 aberration-positive solid tumors, showing particular effectiveness in those ...

7. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/cancer/lung-cancer/fda-approval-hernexeos-first-oral-treatment-her2-mutant-advanced-nsclc

FDA approval HERNEXEOS® first oral treatment HER2- ... Boehringer's new zongertinib data demonstrate durable and clinically meaningful results in patients with HER2 (ERBB2)-mutant advanced NSCLC.