Sacituzumab Govitecan for Breast Cancer

(SERIES Trial)

Recruiting at 2 trial locations

Overseen By Krystal Fernandez

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Reshma L. Mahtani, D.O.

Must not be taking: Corticosteroids, Antibiotics

Disqualifiers: Brain metastases, Serious infection, Pregnancy, 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: 1

Duration: Up to 30 months

75 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to see if the medication sacituzumab govitecan (SG) is effective at the currently approved dose and schedule in people who have previously received trastuzumab deruxtecan (T-DXd) for the treatment of metastatic, hormone receptor positive (HR+)/human epidermal growth factor 2 low (HER2 low) breast cancer. Although SG is approved to treat metastatic HR+/HER2 negative breast cancer, the aim of this study is to determine if SG is still effective specifically in people who have already received T-DXd.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some treatments before starting the study. For example, hormonal therapy and immunotherapy need a 2-week washout period, and T-DXd requires a 3-week washout period. The protocol does not specify if you need to stop all current medications, so it's best to discuss your specific situation with the study team.

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

Sacituzumab Govitecan has shown effectiveness in treating metastatic triple-negative breast cancer (a type of breast cancer that is hard to treat) in patients who have already tried at least two other treatments. It works by delivering a powerful cancer-fighting agent directly to the cancer cells, and it has been approved for use in the USA for this condition. ^{1 2 3 4 5}

Is Sacituzumab Govitecan safe for humans?

Sacituzumab Govitecan has been tested in 408 patients with advanced solid tumors, and common side effects include nausea, low white blood cell count (neutropenia), diarrhea, tiredness, low red blood cell count (anemia), vomiting, hair loss, constipation, skin rash, decreased appetite, and stomach pain. ^{1 2 3 4 6}

How is the drug Sacituzumab Govitecan unique for treating breast cancer?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that specifically targets the Trop-2 protein on cancer cells, delivering a potent chemotherapy agent (SN-38) directly to the tumor, which allows for higher concentrations of the drug at the tumor site compared to standard chemotherapy. ^{1 2 3 4 5}

Research Team

Reshma Mahtani, DO

Principal Investigator

Miami Cancer Institute at Baptist Health, Inc.

Eligibility Criteria

This trial is for individuals with metastatic, hormone receptor positive (HR+)/HER2 low breast cancer who have previously been treated with trastuzumab deruxtecan. Participants must meet specific health criteria to join.

Inclusion Criteria

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

I stopped T-DXd treatment due to worsening or side effects.

Measurable disease as per RECIST V1.1

Exclusion Criteria

My breast cancer is advanced but can still be treated with the goal of curing it.

I do not have any health or mental conditions that could interfere with the study.

I have brain metastases but don't need ongoing steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan (SG) on Days 1 and 8 of continuous 21-day cycles at 10 mg/kg via intravenous (IV) infusion until disease progression or unacceptable toxicity

Up to 30 months

Visits on Days 1 and 8 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24-30 months

Treatment Details

Interventions

• Sacituzumab govitecan

Trial Overview The study tests the effectiveness of sacituzumab govitecan (SG) at its approved dose and schedule in patients who've already received T-DXd for their HR+/HER2 low metastatic breast cancer.

Participant Groups

Group I: Sacituzumab Govitecan (SG) Infusion Experimental Treatment 1 Intervention

SG will be administered on Days 1 and 8 of continuous 21-day cycles at 10 mg/kg via intravenous (IV) infusion until disease progression or unacceptable toxicity.

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

Approved in United States as Trodelvy for:

• Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease
• Locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor
• Unresectable locally advanced or metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting

Approved in European Union as Trodelvy for:

• Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease

Approved in Canada as Trodelvy for:

• Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease

Who Is Running the Clinical Trial?

Reshma L. Mahtani, D.O.

Lead Sponsor

Trials

1

Recruited

80+

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 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]

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 (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]

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-hziy (TRODELVY) received accelerated FDA approval for treating metastatic triple-negative breast cancer (mTNBC) based on a trial involving 108 patients, showing an objective response rate of 33.3% and a median duration of response of 7.7 months.

The safety profile was assessed in a larger group of 408 patients, with common side effects including nausea, neutropenia, and fatigue, occurring in 25% or more of patients, indicating that while effective, the treatment can have significant adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Wahby, S., Fashoyin-Aje, L., Osgood, CL., et al.[2022]

References

1. 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]

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

Sacituzumab Govitecan: First Approval. [2021]

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

5. 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]

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

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022]