Sacituzumab Govitecan + Trastuzumab for Breast Cancer

Recruiting at 4 trial locations

Overseen By Adrienne Waks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Adrienne G. Waks

Must be taking: Taxane, Trastuzumab, T-DXd

Must not be taking: Strong UGT1A1 inhibitors

Disqualifiers: Untreated brain metastases, Leptomeningeal disease, Major surgery, 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

Compensation: Varies

Number of Visits: 28

Duration: 27 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, sacituzumab govitecan (an antibody-drug conjugate) and trastuzumab, to determine their safety and effectiveness in treating metastatic HER2+ breast cancer. The trial seeks to understand how these treatments work together against cancer that has spread beyond the initial tumor site. It is designed for individuals with confirmed metastatic HER2+ breast cancer who have previously undergone certain treatments. Participants must have at least one measurable tumor and must have completed prior treatments, such as chemotherapy, at least two weeks before joining. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

You will need to stop any chemotherapy, biologic treatment, or investigational agents at least 14 days before starting the study treatment. However, you can continue taking bisphosphonates or RANK ligand inhibitors if you are already on them.

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

Research shows that sacituzumab govitecan is generally manageable for patients. One study found it more effective than traditional chemotherapy for some breast cancer patients. However, monitoring for side effects is important. Some patients experienced nausea and low white blood cell counts, which can weaken the immune system.

Trastuzumab, also tested in this trial, is a well-known breast cancer treatment. It has been used for many years and is considered safe. Common side effects include fatigue and fever, but serious side effects are rare.

Both treatments have been used in other contexts, providing a good understanding of their safety. While side effects can occur, they are usually manageable. Patients should always discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sacituzumab Govitecan combined with Trastuzumab for breast cancer because of its unique approach. Sacituzumab Govitecan is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, minimizing damage to healthy cells. This targeted mechanism could lead to more effective treatment with fewer side effects compared to traditional chemotherapy. Additionally, combining it with Trastuzumab, which targets HER2-positive cancer cells, could enhance the overall treatment efficacy, providing a powerful one-two punch against cancer cells. This combination could potentially improve outcomes for patients who have limited options with existing treatments.

What evidence suggests that sacituzumab govitecan and trastuzumab could be effective for metastatic HER2+ breast cancer?

Research has shown that sacituzumab govitecan yields promising results for treating certain breast cancers. It can slow the spread of metastatic breast cancer, even in challenging cases. Trastuzumab is well-known for treating HER2-positive breast cancer by targeting and stopping specific cancer cells from growing. In this trial, researchers are studying the combination of these two treatments, as they might work better together by attacking cancer cells in different ways. Early evidence suggests this combination could be a strong option for people with HER2-positive metastatic breast cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with HER2+ metastatic breast cancer who've had specific prior treatments including a taxane, trastuzumab, and T-DXd. They must have at least one measurable tumor, normal organ function, an ECOG performance status of 0-2, and no major health issues that could interfere with the study. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

I know my cancer's ER and PR status.

Ability to understand and the willingness to sign a written informed consent document

I have a tumor that can be measured by CT scan or MRI.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

I have brain metastases that are either untreated, causing symptoms, or need steroids for symptom control.

I do not have any severe illnesses or conditions that would stop me from following the study's requirements.

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 sacituzumab govitecan and trastuzumab with regular assessments and imaging

27 weeks

CT or MRI scans every 9 weeks, echocardiogram or MUGA scan every 12 weeks

Extended Treatment

Continued treatment with sacituzumab govitecan and trastuzumab with less frequent imaging

Until disease progression or unacceptable toxicity

CT or MRI scans every 12 weeks, echocardiogram or MUGA scan every 16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Follow-up visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan
• Trastuzumab

Trial Overview The trial tests sacituzumab govitecan combined with trastuzumab (Herceptin or similar) to see if they're safe and effective against advanced breast cancer that has worsened after previous treatment. Participants will receive these drugs as part of their therapy regimen.

How Is the Trial Designed?

Group I: Sacituzumab Govitecan + Trastuzumab (or Biosimilar) Experimental Treatment 3 Interventions

Participants will complete the following: * Baseline visit with assessments. * CT or MRI scans every 9 weeks for 27 weeks and then every 12 weeks. * Echocardiogram or MUGA scan every 12 weeks for 24 weeks and then every 16 weeks. * Cycle 1 through Cycle 2: * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * Cycle 2: * Day 1: Optional tumor biopsy * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * Cycle 3 through End of Treatment: * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * End of treatment: * Follow up visits every 6 months.

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?

Adrienne G. Waks

Lead Sponsor

Trials

4

Recruited

240+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

Trastuzumab biosimilars, including MYL-1401O, CT-P6, SB3, PF-05280014, and ABP980, have been approved by the FDA for treating HER2-positive breast cancer, offering potential cost savings and improved access to targeted therapies.

The review highlights the importance of clinical data supporting these biosimilars, suggesting that their adoption in clinical practice will rely on healthcare providers' confidence in the evidence of their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biosimilars for breast cancer: a review of HER2-targeted antibodies in the United States. Miller, EM., Schwartzberg, LS.[2020]

In a study of 17 patients with advanced HER2/neu overexpressing breast cancer, the combination of trastuzumab and paclitaxel resulted in a response rate of 59%, with 2 complete responses and a median overall survival of 23 months.

The treatment was generally well-tolerated, with manageable side effects; however, some patients experienced significant toxicities, including hypersensitivity reactions and grade 3 neuropathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4-years results of weekly trastuzumab and paclitaxel in the treatment of women with HER2/neu overexpressing advanced breast cancer: single institution prospective study. Janku, F., Pribylova, O., Zimovjanova, M., et al.[2015]

In a study of 2,024 Japanese women with HER2-positive early-stage breast cancer, trastuzumab (TZM) demonstrated high efficacy, with a three-year overall survival rate of 98.9% and a disease-free survival rate of 94.2%.

The safety profile of TZM was acceptable, with only 18.8% of patients experiencing adverse events, and serious grade 3/4 adverse events were rare, occurring in just 0.6% of patients, indicating that TZM is a viable treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients. Yamshiro, H., Iwata, H., Masuda, N., et al.[2022]

In a phase IIa study involving 30 patients with advanced gastric cancer, the combination of pertuzumab and trastuzumab showed a well-tolerated safety profile, with partial responses in 86% of patients receiving a specific dosing regimen.

The pharmacokinetics indicated that the serum concentration of pertuzumab was lower in this gastric cancer population compared to those with metastatic breast cancer, leading to the selection of the 840 mg q3w dose for further phase III studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Kang, YK., Rha, SY., Tassone, P., et al.[2021]

Sacituzumab govitecan (IMMU-132) has been shown to prolong progression-free survival in patients with advanced triple-negative breast cancer, indicating its efficacy as a treatment option.

The treatment is well tolerated, resulting in fewer and more manageable side effects compared to traditional irinotecan, suggesting a safer profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An ADC for Triple-Negative Breast Cancer. [2018]

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

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 1/2 trial involving 108 patients with heavily pretreated metastatic triple-negative breast cancer, sacituzumab govitecan-hziy demonstrated a response rate of 33.3%, with a median duration of response of 7.7 months, indicating its efficacy in this challenging patient population.

The treatment was associated with significant myelotoxic effects, including anemia and neutropenia, but overall survival was promising at a median of 13.0 months, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. Bardia, A., Mayer, IA., Vahdat, LT., et al.[2019]

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 (TRODELVY) is an effective treatment for metastatic triple-negative breast cancer, showing promising results in a phase I/II study and receiving accelerated FDA approval for patients who have undergone at least two prior therapies.

The drug has a well-defined and manageable toxicity profile, and proactive management of adverse events is crucial for optimizing treatment duration and maintaining patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. Spring, LM., Nakajima, E., Hutchinson, J., et al.[2021]

Citations

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2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12341277/

Comparison of trastuzumab deruxtecan and sacituzumab ... Comparison of trastuzumab deruxtecan and sacituzumab govitecan in HER2-negative metastatic breast cancer: a large real-world data analysis.

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01199-8/fulltext

Outcomes with trastuzumab deruxtecan by biomarker ... In a large (n = 1490) real-world dataset, T-DXd exhibited favorable activity for metastatic breast cancer (MBC).

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000730

Real-world safety and effectiveness data of trastuzumab ... Real-world safety and effectiveness data of trastuzumab deruxtecan and sacituzumab govitecan in breast cancer: a Hellenic Cooperative Oncology Group study.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13047

Real-world clinical outcome of sacituzumab govitecan (SG) ... While clinical trials have demonstrated the efficacy of SG, real-world data on its use and outcomes remain limited. Methods: This retrospective ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03901339

NCT03901339 | Study of Sacituzumab Govitecan-hziy ... The primary objective of this study is to assess and compare the efficacy and safety of sacituzumab govitecan-hzi versus treatment of physician's choice (TPC)

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11333747/

Efficacy of administration sequence: Sacituzumab Govitecan ... Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer

8. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)01245-X/fulltext

Overall survival with sacituzumab govitecan in hormone ... Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1814213

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple ... Sacituzumab govitecan-hziy was associated with durable objective responses in patients with heavily pretreated metastatic triple-negative breast cancer.