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

Trial Summary

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.

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

Research shows that Sacituzumab Govitecan, a drug used for certain types of breast cancer, can help patients live longer without their cancer getting worse. It is well tolerated and has fewer side effects compared to some other treatments. ^{1 2 3 4 5}

Is the combination of Sacituzumab Govitecan and Trastuzumab safe for humans?

Trastuzumab, used in various forms like Herceptin and its biosimilars, has been studied for safety in breast cancer treatments, showing some cardiac safety concerns when used with other drugs. However, specific safety data for the combination of Sacituzumab Govitecan and Trastuzumab is not provided in the available research. ^{6 7 8 9 10}

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

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that targets a specific protein (Trop-2) on cancer cells and delivers a chemotherapy drug (SN-38) directly to the tumor, which can improve effectiveness and reduce side effects compared to traditional chemotherapy. This combination with Trastuzumab, which targets another protein (HER2) on cancer cells, offers a novel approach for treating certain types of breast cancer. ^{1 3 4 5 11}

What is the purpose of this trial?

This research study is being done to evaluate the safety and effectiveness of sacituzumab govitecan with trastuzumab (Herceptin, Herceptin Hylecta, or trastuzumab biosimilar) in metastatic HER2+ breast cancer. The names of the study drugs used in this research study are: * Sacituzumab govitecan (a type of antibody-drug conjugate) * Trastuzumab (Herceptin) (a type of monoclonal antibody) * Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta) (a type of recombinant monoclonal antibody) * Trastuzumab biosimilar drug

Research Team

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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 (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 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 (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]

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 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]

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 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 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 (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]

References

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

Sacituzumab Govitecan: First Approval. [2021]

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

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

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

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]

4. 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]

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

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

Outcomes of trastuzumab therapy in HER2-positive early breast cancer patients. [2022]

9. France 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. [2015]

10. England 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. [2021]

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

Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. [2021]