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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if blood tests can detect pieces of tumor DNA (ctDNA) to guide treatment decisions for patients with triple-negative breast cancer that has metastasized. Researchers hope that ctDNA results can identify when current chemotherapy is ineffective, allowing doctors to switch to sacituzumab govitecan (Trodelvy), which targets cancer cells more precisely. Eligible participants have metastatic triple-negative breast cancer and have not received chemotherapy for this stage. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sacituzumab govitecan is generally safe for patients with metastatic triple-negative breast cancer (mTNBC). In studies, this treatment consistently proved safe and effective. However, like many cancer treatments, it can cause side effects.

Some patients experienced side effects such as low white blood cell counts, nausea, diarrhea, and tiredness. These were common, but not everyone experienced them. More serious side effects, like very low white blood cell counts, occurred less frequently. Some individuals needed to lower their dose or stop treatment due to side effects.

Overall, sacituzumab govitecan is well-tolerated, but discussing possible side effects with a healthcare provider is important. They can help manage any side effects if they occur. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about sacituzumab govitecan for breast cancer because it offers a novel approach compared to traditional chemotherapy options. Unlike standard treatments that broadly target rapidly dividing cells, sacituzumab govitecan is an antibody-drug conjugate, meaning it combines an antibody with a chemotherapy drug to specifically target and deliver the drug to cancer cells. This targeted approach aims to minimize damage to healthy cells and potentially reduce side effects. Additionally, the use of circulating tumor DNA (ctDNA) to guide treatment decisions allows for a more personalized therapy, adjusting the treatment based on how the cancer responds, which is a cutting-edge advancement in cancer care.

What evidence suggests that this trial's treatments could be effective for metastatic triple-negative breast cancer?

Research shows that sacituzumab govitecan effectively treats metastatic triple-negative breast cancer (mTNBC). Studies have found that it reduces the risk of cancer progression or death by 38% compared to standard chemotherapy. Patients taking sacituzumab govitecan have lived an average of 12.1 months, longer than the 6.7 months observed with other treatments. This drug delivers chemotherapy directly to cancer cells, potentially leading to better outcomes. Real-world evidence also supports its effectiveness and indicates that patients who have tried several other treatments tolerate it well. In this trial, participants in Arm B may receive sacituzumab govitecan based on ctDNA results, while Arm A involves standard chemotherapy without sacituzumab govitecan. ^{3 6 7 8 9}

Who Is on the Research Team?

Vandana Abramson, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 (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]

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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11452463/

Real-world use patterns, effectiveness, and tolerability of ... Sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies.

2. ascopubs.org ascopubs.org/doi/10.1200/OP.24.00242

Real-World Clinical Outcomes With Sacituzumab ... We report the real-world clinical effectiveness and toxicity data of SG in patients with mTNBC.

3. gilead.com gilead.com/news/news-details/2025/trodelvy-reduces-risk-of-disease-progression-or-death-by-38-versus-chemotherapy-as-first-line-therapy-in-patients-with-metastatic-triple-negative-breast-cancer-in-ascent-03-study

Trodelvy Reduces Risk of Disease Progression or Death ... Trodelvy® Reduces Risk of Disease Progression or Death by 38% Versus Chemotherapy as First-Line Therapy in Patients With Metastatic Triple-Negative Breast ...

4. esmoopen.com esmoopen.com/article/S2059-7029(25)01177-9/fulltext

Effectiveness of sacituzumab govitecan and management ... We describe the real-world effectiveness of SG as 2L+ mTNBC treatment and the proportion of patients with neutropenia and its management.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2028485

Sacituzumab Govitecan in Metastatic Triple-Negative ... The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40361516/

The Clinical Outcomes and Safety of Sacituzumab ... Conclusions: SG was associated with similar clinical outcomes and tolerability in both the mTNBC and mHRPBC subtypes. Although the real-world ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S096097762400184X

Safety profile of sacituzumab govitecan in patients with ... The outcomes of interest were absolute risk (AR) of all-grade and grade ≥3 TRAEs: neutropenia; nausea; diarrhea; anemia; febrile neutropenia; alopecia; fatigue; ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41007623/

Effectiveness and Safety of Sacituzumab Govitecan in Real ... Results: A total of 56 patients were included in this study (33 with mTNBC and 23 with HR+/HER2- mBC). In the mTNBC group, mPFS was 4.0 months ( ...

9. onclive.com onclive.com/view/sacituzumab-govitecan-upholds-efficacy-and-safety-in-real-world-mtnbc-population

Sacituzumab Govitecan Upholds Efficacy and Safety in ... Sacituzumab govitecan demonstrated consistent efficacy and safety in real-world mTNBC patients, with median OS of 11.3 months and PFS of 5.0 ...