IAM1363 for Breast Cancer

Recruiting at 29 trial locations

Overseen By Iambic Therapeutics, Inc., Senior Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Iambic Therapeutics, Inc

Disqualifiers: Cardiac disease, HIV, Liver disease, Diabetes, others

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

Compensation: Varies

Number of Visits: 3

243 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IAM1363, a potential drug for individuals with advanced cancers involving changes in the HER2 protein. The primary goal is to determine the safety of IAM1363 and evaluate its effectiveness in treating cancer. Participants will take IAM1363 capsules once or twice daily in 21-day cycles. This trial may suit those whose cancer has returned or worsened after other treatments, particularly if their cancer involves HER2 changes. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that IAM1363 is likely to be safe for humans?

Research has shown that IAM1363 has been tested in patients with advanced cancers involving changes in the HER2 gene. Studies have found that IAM1363 is generally safe and well-tolerated. Some patients experienced side effects, mostly mild to moderate. The treatment has shown promise in fighting cancer cells. While encouraging, this remains early research. The goal is to find the best dose that balances safety and effectiveness. Always consult a healthcare provider to understand the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

IAM1363 is unique because it offers a new approach to treating breast cancer by being administered orally, which could potentially make it more convenient for patients compared to the intravenous delivery of many current treatments like chemotherapy. Researchers are particularly excited about its potential to target cancer cells with less impact on healthy cells, which may lead to fewer side effects. Additionally, IAM1363 is designed to be taken in 21-day cycles, providing a structured and potentially more manageable treatment schedule.

What evidence suggests that IAM1363 might be an effective treatment for advanced cancers with HER2 alterations?

Research shows that IAM1363, administered as monotherapy in this trial, effectively targets tumors in cancers with HER2 changes. Early studies suggest it is safe and generally well-tolerated by patients. The drug contains entinostat, linked to longer survival in breast cancer patients. Initial results from these studies are promising, indicating potential effectiveness against advanced cancers. However, further research is needed to fully understand its benefits. ^{1 2 3 4 6}

Who Is on the Research Team?

Iambic Therapeutics, Inc., Senior Medical Director

Principal Investigator

Iambic Therapeutics, Inc

Are You a Good Fit for This Trial?

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 fully active or can carry out light work.

Exclusion Criteria

I have a serious heart condition.

I have HIV but it is well-controlled.

My diabetes is not under control.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• IAM1363
• Trastuzumab

Trial Overview 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.

How Is the Trial Designed?

Group I: IAM1363 Monotherapy Experimental Treatment 1 Intervention

Treatment with IAM1363 capsules, dosed orally either once or twice daily in 21-day cycles.

Who Is Running the Clinical Trial?

Iambic Therapeutics, Inc

Lead Sponsor

Trials

1

Recruited

240+

Published Research Related to This Trial

In a study of 94 estrogen receptor-positive breast tumors, higher levels of IFITM1 were linked to advanced clinical stages and poor responses to endocrine therapy, indicating its potential role in endocrine resistance.

Knocking down IFITM1 in AI-resistant breast cancer cells reduced tumor growth and invasion, while its overexpression in sensitive cells led to more aggressive growth, suggesting that targeting IFITM1 could be a promising strategy for treating endocrine-resistant breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21. Lui, AJ., Geanes, ES., Ogony, J., et al.[2021]

In the EMILIA phase 3 study, trastuzumab emtansine (T-DM1) significantly delayed the time to symptom worsening in patients with HER2-positive breast cancer, with a duration of 7.1 months compared to 4.6 months for capecitabine and lapatinib.

Patients treated with T-DM1 experienced a lower incidence of diarrhea symptoms during treatment, maintaining levels near baseline, while those on capecitabine and lapatinib saw a 1.5- to 2-fold increase, indicating better tolerability for T-DM1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Welslau, M., Diéras, V., Sohn, JH., et al.[2022]

Trastuzumab emtansine (T-DM1) shows comparable pharmacokinetics across different ethnic groups, indicating that the recommended dosing is appropriate for all, based on data from 671 patients across multiple studies.

While ethnicity did not significantly affect the efficacy or safety of T-DM1, there was a noted trend of increased risk for thrombocytopenia in Asian patients, although most were able to continue treatment with dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer. Li, C., Wang, B., Lu, D., et al.[2022]

The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor entinostat (ENT) significantly reduced HER2 expression and tumor viability in aromatase inhibitor (AI)-resistant breast cancer cells, indicating a potential mechanism to overcome resistance.

In animal models, the ATRA + ENT combination, especially when paired with letrozole, led to a notable decrease in tumor growth and tumor-initiating cell characteristics, suggesting that this treatment strategy could effectively reduce the risk of tumor recurrence in AI-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histone deacetylase inhibitor entinostat in combination with a retinoid downregulates HER2 and reduces the tumor initiating cell population in aromatase inhibitor-resistant breast cancer. Schech, AJ., Shah, P., Yu, S., et al.[2018]

Lurbinectedin demonstrated a significant objective response rate of 41% in patients with BRCA1/2 mutations, indicating its efficacy in treating metastatic breast cancer, particularly in those with BRCA2 mutations who had an even higher response rate of 61%.

The safety profile of lurbinectedin improved with dose adjustments, although common side effects included nausea and fatigue, with neutropenia being the most severe hematologic adverse event, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy. Cruz, C., Llop-Guevara, A., Garber, JE., et al.[2019]

In a meta-analysis of 5,045 breast cancer patients, T-DM1 treatment was linked to a significantly increased risk of severe adverse events, including thrombocytopenia (10.66 times higher risk) and anemia (1.68 times higher risk).

While the overall incidence of severe adverse events is low, T-DM1 can lead to serious conditions such as elevated liver enzymes, hypertension, and peripheral sensory neuropathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Liu, K., Li, YH., Zhang, X., et al.[2022]

In the phase III MARIANNE trial involving patients with previously untreated HER2-positive metastatic breast cancer, trastuzumab emtansine (T-DM1) did not show predictive biomarker benefits for progression-free survival (PFS) compared to trastuzumab plus taxane, indicating that HER2-related biomarkers may not guide treatment decisions effectively.

However, higher HER2 mRNA levels and mutated PIK3CA status were found to be prognostic for PFS, suggesting that while they do not predict treatment response, they may provide insights into patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Perez, EA., de Haas, SL., Eiermann, W., et al.[2020]

The combination of entinostat and exemestane has been shown to improve survival rates in women with estrogen receptor-positive (ER+) advanced breast cancer.

This finding suggests that entinostat may enhance the effectiveness of exemestane, a common treatment for this type of cancer, potentially offering a new therapeutic strategy for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Entinostat plus exemestane has activity in ER+ advanced breast cancer. [2016]

In a study of 232 Japanese patients with HER2-positive advanced breast cancer, trastuzumab emtansine (T-DM1) was found to be well tolerated, with 98.3% of patients experiencing adverse events but only 2.2% discontinuing treatment due to these events.

The most common serious adverse effects included thrombocytopenia in 29.7% of patients and hepatotoxicity in 11.2%, but no new safety concerns were identified, indicating that T-DM1 is a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer. Watanabe, J., Ito, Y., Saeki, T., et al.[2022]

The Breast Cancer Index (BCI) biomarker effectively predicts which early-stage hormone receptor-positive breast cancer patients will benefit from extended endocrine therapy (EET) with letrozole, showing a significant reduction in recurrence risk for those with high BCI scores.

Approximately 50% of patients identified as high-risk by clinical criteria did not benefit from extended therapy, while those with low-risk profiles showed significant improvement, highlighting the importance of personalized treatment plans based on BCI results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy. Noordhoek, I., Treuner, K., Putter, H., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06253871

A Phase 1/1b Study of IAM1363 in HER2 Cancers This is a Phase 1/1b open-label, multi-center study, designed to evaluate IAM1363 in participants with advanced cancers that harbor HER2 alterations.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS3186

IAM1363-01: A phase 1/1b study of a selective and brain- ... IAM1363-01 is a first-in-human, multicenter, open-label, Phase 1/1b dose escalation and expansion trial evaluating IAM1363 as monotherapy and in combination ...

3. withpower.com withpower.com/trial/phase-1-cancers-harboring-her2-alterations-1-2024-77124

IAM1363 for Breast Cancer What data supports the effectiveness of the drug IAM1363 for breast cancer? Research shows that entinostat, a component of IAM1363, can improve survival in ...

4. iambic.ai iambic.ai/post/esmo-iam1363

Iambic Shares Clinical Data from Ph1/1B Study of IAM1363 ... AI-designed oncology drug candidate IAM1363 showed clinical anti-tumor activity, safety, and tolerability. IAM1363 shown to be active across ...

5. bcan.org bcan.org/clinicaltrials/iam1363-in-her2-cancers/

IAM1363 in HER2 Cancers This is a Phase 1/1b open-label, multi-center study, designed to evaluate IAM1363 in participants with advanced cancers that harbor HER2 alterations.

6. finance.yahoo.com finance.yahoo.com/news/iambic-shares-clinical-data-ph1-110000286.html

Iambic Shares Clinical Data from Ph1/1B Study of IAM1363 ... AI-designed oncology drug candidate IAM1363 showed clinical anti-tumor activity, safety, and tolerability. IAM1363 shown to be active across ...