ctDNA-Guided Chemotherapy for Breast Cancer

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt-Ingram Cancer Center

Must not be taking: Hormone contraceptives, Bisphosphonates

Disqualifiers: Leptomeningeal disease, Uncontrolled pain, Hypercalcemia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to 3 years

160 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that concurrent anti-cancer therapy other than the ones specified in the protocol is not allowed, so you may need to discuss your current medications with the study team.

What data supports the effectiveness of the drug Sacituzumab Govitecan for breast cancer?

The research highlights the potential of using circulating tumor DNA (ctDNA) to guide treatment decisions in breast cancer, similar to its use in other cancers. While specific data on Sacituzumab Govitecan is not provided, the studies suggest that ctDNA can help identify patients who might benefit from targeted therapies, which could include drugs like Sacituzumab Govitecan. ^{1 2 3 4 5}

Is sacituzumab govitecan safe for humans?

Sacituzumab govitecan has been studied for safety in various types of cancer, including breast cancer, and has received approval for use in certain cases. It has been evaluated in clinical trials for different cancers, showing it is generally safe for human use, although like all treatments, it may have side effects. ^{6 7 8 9 10}

What makes the drug Sacituzumab Govitecan unique for breast cancer treatment?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate (a combination of an antibody and a drug) that targets a protein called Trop-2, which is found on many cancer cells, and delivers a chemotherapy drug directly to these cells. This targeted approach can help treat certain types of breast cancer that have limited treatment options, especially after other therapies have failed. ^{6 8 10 11 12}

What is the purpose of this trial?

This phase II trial tests how well evaluating circulating tumor deoxyribonucleic acid (ctDNA) works to guide therapy-change decisions in treating patients with triple-negative breast cancer (TNBC) that has spread from where it first started (primary site) to other places in the body (metastatic). This study wants to learn if small pieces of DNA associated with a tumor (called circulating tumor DNA, or ctDNA) can be detected in investigational blood tests during the course of standard chemotherapy treatment for breast cancer, and whether information from such investigational ctDNA blood testing could possibly be used as an early indication of chemotherapy treatment failure. It is hoped that additional information from investigational blood testing for ctDNA could help doctors to switch more quickly from a standard chemotherapy treatment that typically has significant side effects and which may not be working, to a different standard treatment regimen against TNBC, called sacituzumab govitecan. Sacituzumab govitecan is a monoclonal antibody, called hRS7, linked to a chemotherapy drug, called irinotecan. hRS7 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers irinotecan to kill them. Studying ctDNA may assist doctors to change therapy earlier if needed, and may improve health outcomes in patients with metastatic TNBC.

Research Team

Vandana Abramson, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

This trial is for adults with metastatic triple-negative breast cancer (TNBC) who haven't had chemotherapy for their advanced disease. They should have normal liver function or slightly elevated levels if liver metastases are present, an ECOG performance status of 0-2, and be PD-L1 negative or unsuitable for checkpoint inhibitors. Participants must not be pregnant, breastfeeding, have other cancers within the last 5 years (except low-risk types), uncontrolled diseases/pain/hypercalcemia, significant heart disease, psychiatric issues affecting compliance, or major surgery within 4 weeks before the trial.

Inclusion Criteria

Your liver tests show that your bilirubin, SGOT, and SGPT levels are not too high, especially if you have liver metastases.

Your absolute neutrophil count (ANC) is at least 1000 per cubic millimeter within the last 28 days before starting the study drug.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I haven't had any cancer other than triple-negative breast cancer in the last 5 years.

I am not on any cancer treatments not listed in the study protocol.

My cancer pain is not managed with current treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive standard of care chemotherapy and undergo blood sample collection for ctDNA evaluation. Possible treatment change to sacituzumab govitecan based on ctDNA results.

Up to 3 years

Regular visits for chemotherapy and ctDNA evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

Follow-up at 3, 6, 9, and 12 months, then every 6 months

Treatment Details

Interventions

• Sacituzumab Govitecan

Trial Overview The study tests whether monitoring circulating tumor DNA (ctDNA) can guide when to switch from standard chemotherapy to sacituzumab govitecan—a targeted therapy combining a monoclonal antibody with a chemo drug—in patients with spreading TNBC. The goal is to see if ctDNA can indicate early on if the current treatment isn't working and help shift patients sooner to potentially more effective treatments.

Participant Groups

Group I: Arm B (biospecimen evaluation, possible treatment change) Experimental Treatment 4 Interventions

Patients receive providers choice of standard of care chemotherapy and undergo blood sample collection for ctDNA evaluation on study. Patients may receive sacituzumab govitecan IV based on ctDNA results on study. Patients undergo CT or MRI during screening and on study.

Group II: Arm A (biospecimen banking) Active Control 3 Interventions

Patients receive providers choice of standard of care chemotherapy and undergo blood sample collection for banking on study. Patients undergo CT or MRI during screening and on study.

Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer
• Locally advanced or metastatic urothelial cancer (withdrawn)
• Metastatic HR+/HER2- breast cancer

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Sacituzumab govitecan (SG) showed a clinically significant advantage over chemotherapy for treating HR+/HER2- metastatic breast cancer, providing an increase of 0.284 life years and 0.217 quality-adjusted life years (QALYs).

However, SG was not considered cost-effective at the current pricing, with an incremental cost-effectiveness ratio (ICER) of $612,772/QALY, indicating that substantial price reductions would be necessary for it to be deemed cost-effective from a third-party payer perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Shi, D., Li, Y., Liang, X., et al.[2023]

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) in patients with endocrine-resistant HR+/HER2- metastatic breast cancer, showing a 34% reduction in the risk of progression or death compared to standard chemotherapy.

The safety profile of SG was manageable, with notable grade ≥ 3 adverse events including neutropenia and diarrhea, but it still represents a promising treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. Rugo, HS., Bardia, A., Marmé, F., et al.[2023]

In a phase 3 trial involving 543 patients with pretreated, endocrine-resistant HR+ and HER2- metastatic breast cancer, sacituzumab govitecan significantly improved overall survival compared to chemotherapy, with a median survival of 14.4 months versus 11.2 months.

Sacituzumab govitecan also showed a higher objective response rate (21% vs 14%) and better quality of life outcomes, indicating it is a promising new treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Rugo, HS., Bardia, A., Marmé, F., et al.[2023]

Sacituzumab govitecan is an FDA-approved antibody-drug conjugate that effectively targets Trop-2, which is overexpressed in various solid tumors, including metastatic triple-negative breast cancer and urothelial carcinoma.

This drug combines an anti-Trop-2 antibody with the SN-38 payload, an active metabolite of irinotecan, showcasing a novel mechanism of action that enhances the delivery of potent anticancer agents directly to tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers. Vranic, S., Gatalica, Z.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Identification of mutation patterns and circulating tumour DNA-derived prognostic markers in advanced breast cancer patients. [2023]

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

Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer. [2023]

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

Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial. [2021]

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

Use of ctDNA Guides Panitumumab Rechallenge Efficacy in Colorectal Cancer. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021]

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

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

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. [2023]

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

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. [2023]

12. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers. [2022]