89Zr-ss-pertuzumab Imaging for Breast Cancer

Not currently recruiting at 7 trial locations

Overseen By Randy Yeh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Life expectancy < 3 months, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 20 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging treatment called 89Zr-ss-pertuzumab to determine its safety for individuals with certain types of breast cancer. It targets those with HER2-positive cancer, characterized by high levels of a protein that promotes cancer cell growth, and HER2-low cancer. Participants must have a confirmed diagnosis of primary or metastatic HER2-positive or HER2-low breast cancer that affects their daily life. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that 89Zr-ss-pertuzumab is safe for people with HER2+ cancer?

Research has shown that 89Zr-ss-pertuzumab, a drug under study for treating HER2-positive cancer, has been tested in humans before. In a study involving patients with HER2-positive breast cancer, researchers examined the safety of 89Zr-ss-pertuzumab, focusing on how the body processed and distributed the drug.

This study found no major safety issues. Most patients tolerated the treatment well, experiencing no serious side effects. While some mild side effects can occur, they are usually manageable and not severe.

This marks the first time this specific drug has been tested in humans, so the primary focus is on ensuring safety. As this is an early phase of research, the main goal is to assess safety and understand how patients respond to the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of 89Zr-ss-pertuzumab for imaging in breast cancer because it offers a novel approach to targeting HER2-positive and HER2-low malignancies. Unlike traditional imaging methods, which may not specifically highlight HER2 expression, 89Zr-ss-pertuzumab is a radiolabeled antibody that binds directly to the HER2 protein on cancer cells, potentially providing clearer and more precise imaging. This specificity could help in better assessing the extent of the disease and in monitoring treatment responses more effectively. By improving imaging accuracy, this approach could lead to more personalized and effective treatment plans for patients.

What evidence suggests that 89Zr-ss-pertuzumab is effective for HER2+ cancer?

Research has shown that 89Zr-ss-pertuzumab PET/CT imaging effectively checks the HER2 status in cancer patients. This imaging helps determine the amount of HER2 protein in tumors, which is crucial for treatment planning. In earlier studies, researchers used this imaging to guide biopsies and decide on subsequent treatment steps when cancer progressed. Additionally, evidence from similar imaging methods suggests that this approach can more accurately assess tumor response to treatment. This trial will evaluate the effectiveness of 89Zr-ss-pertuzumab imaging in participants with HER2-positive or HER2-low breast cancer, as it could help tailor treatment more precisely. ^{1 2 3 6 7}

Who Is on the Research Team?

Somali Gavane, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HER2+ breast cancer, as defined by specific medical guidelines or genetic testing. Participants must have at least one detectable cancer lesion and be in fair to good physical condition (ECOG 0-2). Pregnant or breastfeeding individuals, those with certain kidney or liver conditions, a life expectancy under three months, or who exceed the weight limit for PET/CT scans cannot join.

Inclusion Criteria

My cancer is HER2 positive based on specific guidelines or tests.

My cancer has low HER2 levels, confirmed by specific tests.

My cancer is confirmed to be HER2-positive or HER2-low.

Exclusion Criteria

Your liver enzymes (AST/ALT) are more than double the normal limit.

Pregnancy or lactation

Your kidney function, measured by a blood test called creatinine, is more than double the normal level.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 89Zr-ss-pertuzumab to evaluate its safety in HER2+ cancer

Up to 20 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 89Zr-ss-pertuzumab

Trial Overview The study is evaluating the safety of a new imaging agent called 89Zr-ss-pertuzumab used in PET/CT scans to identify cancer in patients with HER2+ breast cancer. It aims to determine if this agent can effectively highlight tumors during imaging.

How Is the Trial Designed?

Group I: HER2-positive malignancy Experimental Treatment 1 Intervention

Participants will have a diagnosis of HER2-positive malignancy

Group II: HER2-low malignancy Experimental Treatment 1 Intervention

Participants will have a diagnosis of HER2-low malignancy

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The study successfully developed an immuno-PET imaging agent, 89Zr-DFO-pertuzumab, which effectively binds to HER2 and allows for visualization of HER2-expressing tumors, demonstrating its potential to monitor therapeutic responses in breast cancer.

In trastuzumab-resistant JIMT-1 breast cancer models, 89Zr-DFO-pertuzumab showed significantly reduced uptake in tumors treated with the HSP90 inhibitor 17-DMAG, indicating its ability to assess treatment efficacy and HER2 downregulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Response Monitoring with 89Zr-DFO-Pertuzumab in HER2-Positive and Trastuzumab-Resistant Breast Cancer Models. Kang, M., Shin, JI., Han, S., et al.[2022]

This first-in-human study involving 6 patients with HER2-positive metastatic breast cancer demonstrated that 89Zr-pertuzumab PET/CT is safe, with no reported toxicities during the trial.

The imaging technique effectively visualized HER2-positive metastases, confirming its potential for assessing HER2 status in lesions that are difficult to biopsy, and it accurately identified HER2-positive brain metastases in one patient, which was later confirmed by surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer. Ulaner, GA., Lyashchenko, SK., Riedl, C., et al.[2019]

Pertuzumab is an effective treatment for metastatic HER2-positive breast cancer, especially when combined with trastuzumab and docetaxel, showing significant improvements in progression-free and overall survival in treatment-naive patients.

As a HER dimerization inhibitor, pertuzumab works differently than trastuzumab, allowing for a more complete blockade of HER2 signaling, and has a tolerable safety profile, making it a recommended first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer. Chung, C., Lam, MS.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38272704/

First-in-Human Evaluation of Site-Specifically Labeled 89 Zr ... 89 Zr-ss-pertuzumab PET/CT was used to assess HER2 status and heterogeneity to guide biopsy and decide the next line of treatment at progression.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10605041/

89Zr-Trastuzumab PET/CT Imaging of HER2-Positive ... Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/65/3/386.abstract

First-in-Human Evaluation of Site-Specifically Labeled 89Zr ... 89 Zr-ss-pertuzumab PET/CT was used to assess HER2 status and heterogeneity to guide biopsy and decide the next line of treatment at progression.

4. nature.com nature.com/articles/s41523-023-00587-2

Pertuzumab plus high-dose trastuzumab for HER2-positive ... The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive ...

5. mdpi.com mdpi.com/1420-3049/26/6/1568

[ 89 Zr]-Pertuzumab PET Imaging Reveals Paclitaxel ... This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models.

6. ijprajournal.com ijprajournal.com/issue_dcp/Pertuzumab%20in%20Her2%20Positive%20Breast%20Cancer%20Review.pdf

Pertuzumab in Her2 Positive Breast Cancer: Review The study found that the combination of pertuzumab, trastuzumab, and chemotherapy led to improved outcomes in patients with HER2-positive breast.

7. researchgate.net researchgate.net/publication/377716996_First-in-Human_Evaluation_of_Site-Specifically_Labeled_89_Zr-Pertuzumab_in_Patients_with_HER2-Positive_Breast_Cancer

First-in-Human Evaluation of Site-Specifically Labeled 89 ... Here, we describe a first-in-human PET study on patients with HER2-positive breast cancer evaluating the safety, biodistribution, and dosimetry ...