BI 1810631 for Advanced Cancer
Recruiting in Palo Alto (17 mi)
+89 other 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.12345
What makes the drug BI 1810631 unique for treating advanced cancer?
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:
See 31 more
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.
See 9 more
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 OverviewThe 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
9Treatment groups
Experimental Treatment
Group I: Phase Ib - Dose expansion part: Cohort 8Experimental Treatment1 Intervention
Cohort only in the United States of America (USA)
Group II: Phase Ib - Dose expansion part: Cohort 7Experimental Treatment1 Intervention
Cohort only in Japan
Group III: Phase Ib - Dose expansion part: Cohort 6Experimental Treatment1 Intervention
Cohort only in the United States of America (USA)
Group IV: Phase Ib - Dose expansion part: Cohort 5Experimental Treatment1 Intervention
Group V: Phase Ib - Dose expansion part: Cohort 4Experimental Treatment1 Intervention
Group VI: Phase Ib - Dose expansion part: Cohort 3Experimental Treatment1 Intervention
Group VII: Phase Ib - Dose expansion part: Cohort 2Experimental Treatment1 Intervention
Group VIII: Phase Ib - Dose expansion part: Cohort 1Experimental Treatment1 Intervention
Group IX: Phase Ia - Dose escalation partExperimental Treatment1 Intervention
Consecutive cohorts of patients treated with escalating doses of BI 1810631 monotherapy.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Tennessee Oncology, PLLCNashville, TN
Winship Cancer InstituteAtlanta, GA
Hawaii Cancer Care - HonoluluHonolulu, HI
Duke University Medical CenterDurham, NC
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Boehringer IngelheimLead Sponsor
References
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.
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.
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.
The role of adjuvant monoclonal antibody therapy for breast cancer: rationale and new studies. [2019]HER2 is a member of the epidermal growth factor receptor (EGFR) family of tyrosine kinases and is involved in the growth, invasion, metastasis, and prognosis of breast cancer. The rationale for prospective trials evaluating the role of anti-HER2 monoclonal antibody therapy for patients with high-risk HER2-positive resected breast cancer is based on several factors. These include 1) the relative and absolute poor prognosis of patients with node-positive, HER2-positive breast cancer; 2) the emerging data of potential importance concerning anthracyclines as a component of adjuvant therapy for patients with HER2-positive breast cancer; 3) the role of taxanes in the management of patients with HER2-positive metastatic breast cancer; and 4) the feasibility and efficacy of molecularly targeted anti-HER2 monoclonal antibody treatment alone or in combination with chemotherapy for patients with advanced breast cancer.
New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?pi. [2020]Over the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine. The management of this breast cancer subgroup has thus been revolutionized and its prognosis has changed dramatically. Nevertheless, HER2-positive advanced breast cancer remains an incurable disease and resistance to conventional anti-HER2 drugs is almost unavoidable. Nowadays, biochemical and pharmaceutical advances are meeting the challenge of developing increasingly sophisticated therapies directed against HER2, including novel anti HER2 antibodies with increased affinity. New antibody-drug conjugates (ADC) with more advanced pharmacological properties, and dual targeting of epitopes via bispecific monoclonal antibodies are also emerging. In addition, more potent and more specific HER2 tyrosine kinase inhibitors have shown interesting outcomes and are under development. Finally, researchers' interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.
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]BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804).
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).
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]To evaluate the efficacy and safety of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in metastatic breast cancer (MBC).
Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4). [2023]ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions.