BI 1810631 for Advanced Cancer

Recruiting at 88 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Boehringer Ingelheim

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

Disqualifiers: Major surgery, Previous malignancies, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called BI 1810631, which is taken as tablets. It targets adults with advanced cancers that have specific genetic changes and have not responded to other treatments. The goal is to find a safe dose and see if it can help shrink tumors.

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.

What data supports the effectiveness of the drug BI 1810631 for advanced cancer?

Research on similar drugs, like poziotinib, shows promising results in treating cancers with HER2 mutations, which are similar to the target of BI 1810631. These drugs have shown effectiveness in non-small cell lung cancer and breast cancer by targeting the HER2 protein, which is involved in cancer growth. ^{1 2 3 4 5}

What makes the drug BI 1810631 unique for treating advanced cancer?

BI 1810631 is unique because it specifically targets HER2 receptors with exon 20 mutations, which are not effectively addressed by many existing treatments, and it does so while sparing EGFR signaling, potentially reducing side effects. ^{1 6 7 8 9}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• BI 1810631 (Small Molecule Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. 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]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?pi. [2020]

6. 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]

7. 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]

8. Germany 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. [2022]

9. United States 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). [2023]