IAM1363 for Breast Cancer
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Iambic Therapeutics, Inc
Disqualifiers: Cardiac disease, HIV, Liver disease, Diabetes, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a Phase 1/1b open-label, multi-center dose escalation and dose optimization study designed to evaluate the safety and preliminary efficacy of IAM1363 in participants with advanced cancers that harbor HER2 alterations.
Do I need to stop my current medications for the trial?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug IAM1363 for breast cancer?
Research shows that entinostat, a component of IAM1363, can improve survival in women with advanced breast cancer when combined with another drug, exemestane. Additionally, entinostat has been shown to reduce tumor growth and resistance in certain breast cancer cells.
12345Is IAM1363 (also known as Trastuzumab or Herceptin) safe for humans?
Research shows that Trastuzumab emtansine (T-DM1), a form of IAM1363, has been studied for safety in patients with breast cancer. While it is generally considered safe, some patients may experience severe side effects, so it's important to discuss potential risks with a healthcare provider.
678910Eligibility Criteria
This trial is for adults with advanced cancers that have HER2 alterations. Participants must be able to receive treatment and provide a tumor sample. Specific details on who can or cannot participate are not provided.Inclusion Criteria
My cancer has returned or didn't respond to treatment and involves a change in the HER2 gene.
Have radiographically measurable disease assessable by RECIST v1.1
I am 18 years old or older.
+4 more
Exclusion Criteria
I have a serious heart condition.
I have HIV but it is well-controlled.
My diabetes is not under control.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Monotherapy Dose Escalation
Participants with confirmed HER2 alterations receive IAM1363 to determine the maximum tolerated dose
21 days
3 visits (in-person)
Dose Optimization
Additional cohorts are enrolled to optimize dose selection and evaluate safety and preliminary efficacy
Estimated 3 months
Simon 2-Stage Evaluation
Tumor-specific cohorts are enrolled to evaluate IAM1363 at the selected dose(s) using a Simon 2-Stage Minimax Design
Estimated 46 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
30 days after the last dose
Participant Groups
The study is testing IAM1363, both alone and combined with Trastuzumab, to see how safe it is and if it works against advanced HER2-altered cancers. It's an early-stage trial where doses will be adjusted to find the right balance between safety and effectiveness.
1Treatment groups
Experimental Treatment
Group I: IAM1363 MonotherapyExperimental Treatment1 Intervention
Treatment with IAM1363 capsules, dosed orally either once or twice daily in 21-day cycles.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Comprehensive Hematology OncologySaint Petersburg, FL
OU Health Stephenson Cancer CenterOklahoma City, OK
SCRI Oncology PartnersNashville, TN
Mary Crowley Cancer ResearchDallas, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Iambic Therapeutics, IncLead Sponsor
References
Entinostat plus exemestane has activity in ER+ advanced breast cancer. [2016]Adding entinostat to exemestane improves survival in women with ER(+) advanced breast cancer.
Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer. [2018]Resistance to aromatase inhibitors (AIs) involves increased HER2. One mechanism by which HER2 may mediate resistance is through expansion of the tumor initiating cell (TIC) population. This study investigates whether combining all-trans retinoic acid (ATRA) and histone deacetylase inhibitor entinostat (ENT) can inhibit TICs and HER2 in AI-resistant cells and tumors. Modulation of cell viability and HER2 expression were assessed in AI-resistant cells treated with ATRA + ENT. Letrozole-resistant LTLT-Ca cells treated with ATRA + ENT were assayed for changes in TIC characteristics, such as TIC markers (BCRP, ALDH, and BMI-1), side population (SP), and mammosphere formation. Xenograft tumors of MCF-7Ca cells made resistant to letrozole were treated with ATRA, ATRA + letrozole, ATRA + ENT, or ATRA + ENT + letrozole. Resulting tumors were assayed for changes in TIC characteristics. Patient samples taken pre- and post-AI treatment were analyzed for changes in ERα and HER2 protein expression. Treatment with ATRA + ENT reduced HER2 expression and viability (P
Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy. [2022]Label="PURPOSE">Individualized selection of patients with early-stage hormone receptor-positive (HR+) breast cancer for extended endocrine therapy (EET) is required to balance modest gains in outcome with toxicities of prolonged use. This study examined the Breast Cancer Index [BCI; HOXB13/IL17BR ratio (H/I)] as a predictive biomarker of EET benefit in patients from the Investigation on the Duration of Extended Adjuvant Letrozole trial.
IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21. [2021]Interferon induced transmembrane protein 1 (IFITM1) belongs to a family of interferon stimulated genes (ISGs) that is associated with tumor progression and DNA damage resistance; however, its role in endocrine resistance is not known. Here, we correlate IFITM1 expression with clinical stage and poor response to endocrine therapy in a tissue microarray consisting of 94 estrogen receptor (ER)-positive breast tumors. IFITM1 overexpression is confirmed in the AI-resistant MCF-7:5C cell line and not found in AI-sensitive MCF-7 cells. In this study, the orthotopic (mammary fat pad) and mouse mammary intraductal (MIND) models of breast cancer are used to assess tumor growth and invasion in vivo. Lentivirus-mediated shRNA knockdown of IFITM1 in AI-resistant MCF-7:5C cells diminished tumor growth and invasion and induced cell death, whereas overexpression of IFITM1 in wild-type MCF-7 cells promoted estrogen-independent growth and enhanced their aggressive phenotype. Mechanistic studies indicated that loss of IFITM1 in MCF-7:5C cells markedly increased p21 transcription, expression and nuclear localization which was mediated by JAK/STAT activation. These findings suggest IFITM1 overexpression contributes to breast cancer progression and that targeting IFITM1 may be therapeutically beneficial to patients with endocrine-resistant disease.
Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy. [2019]This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance.
Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. [2022]This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer.
Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. [2022]Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab.
Incidence and risk of severe adverse events associated with trastuzumab emtansine (T-DM1) in the treatment of breast cancer: an up-to-date systematic review and meta-analysis of randomized controlled clinical trials. [2022]We performed an up-to-date meta-analysis to quantify the overall incidence and risk of severe adverse events (AEs) associated with T-DM1 in patients with breast cancer.
Relationship between tumor biomarkers and efficacy in MARIANNE, a phase III study of trastuzumab emtansine ± pertuzumab versus trastuzumab plus taxane in HER2-positive advanced breast cancer. [2020]The phase III EMILIA and TH3RESA trials demonstrated clinical benefits of trastuzumab emtansine (T-DM1) therapy in patients with previously treated HER2-positive metastatic breast cancer (MBC). Data from these and other trials showed that T-DM1-associated survival benefits were observed across biomarker subgroups tested in these trials. Prespecified, exploratory analyses of the phase III MARIANNE study examined the effects of HER2-related biomarkers on PFS in patients administered T-DM1 in the first-line MBC setting.
Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer. [2022]Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities.