Sacituzumab Govitecan for Breast Cancer

Overseen By Stephen Chia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: British Columbia Cancer Agency

Must be taking: CDK4/6 inhibitors

Disqualifiers: Active second malignancy, Uncontrolled diarrhea, 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: 5

Duration: Until disease progression or significant toxicity

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients with stable doses of anticonvulsants and corticosteroids can participate, suggesting some medications may be allowed.

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

Research shows that Sacituzumab Govitecan, a drug that targets a protein on cancer cells, helps patients with advanced triple-negative breast cancer live longer without the disease getting worse. It is also well tolerated, with fewer side effects compared to similar treatments. ^{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, rash, decreased appetite, and abdominal pain. ^{1 2 5 6 7}

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 can lead to higher concentrations of the drug at the tumor site and potentially better outcomes for patients with metastatic triple-negative breast cancer who have already tried other treatments. ^{1 2 4 5 7}

What is the purpose of this trial?

Advanced hormone positive (HR+), HER2 negative breast cancer continues to pose a challenge when patients have progressed on CDK4/6 inhibitor and endocrine therapy leaving limited treatment options. Antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have changed practice due to significant improvement in progression free survival (PFS) and overall survival (OS) seen in this disease setting. There is a genuine interest to use SG sequentially after T-DXd, however there is no current prospectively curated evidence to support this strategy. Though the epitope is different, the payload are both topoisomerase I inhibitors. Thus, evidence is needed of both clinical efficacy and identification of mechanisms of sensitivity and resistance to sequential ADCs in HER-2 low MBC. It is hypothesized that performing whole genome and whole transcriptome sequencing in fresh tumour biopsies post progression of T-DXd and prior to SG in ER+/HER2 low metastatic breast cancer (MBC) will provide mechanistic insights into identifying biomarkers, and thus patients, sensitive to sequential SG.

Eligibility Criteria

This trial is for individuals with advanced hormone-positive, HER2-negative metastatic breast cancer who have already undergone treatment with CDK4/6 inhibitors and endocrine therapy. Participants will be selected based on their genetic makeup from tumor biopsies to find those likely to respond to the study drug.

Inclusion Criteria

Willing and able to provide signed informed consent approved by UBC/BC Cancer REB

My breast cancer is ER+ and HER2 low, and it has spread.

My tumor can be safely biopsied for genetic testing.

Exclusion Criteria

My tumor cannot be safely biopsied.

Pregnancy and breast feeding

I am not open to considering treatments that affect my whole body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Biopsy and Sequencing

Tumor specimens are collected from biopsies, and whole genome and transcriptome sequencing is performed

3 weeks

1 visit (in-person)

Treatment

Patients receive sacituzumab govitecan (SG) at an initial dose of 10 mg per kilogram intravenously on day 1 and 8 of 21 day cycles

Until disease progression or significant toxicity

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

Regular visits (in-person)

Treatment Details

Interventions

• Sacituzumab Govitecan

Trial Overview The trial tests Sacituzumab Govitecan (SG) in patients after they've progressed following Trastuzumab Deruxtecan (T-DXd) treatment. It aims to understand if SG can be effective when used sequentially and identify genomic markers predicting response.

Participant Groups

Group I: Sacituzumab Govitecan Experimental Treatment 1 Intervention

Patients will receive SG at an initial dose of 10 mg per kilogram intravenously on day 1 and 8 of 21 day cycles.

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?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

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]

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]

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]

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-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]

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]

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

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

4. 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]

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

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

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]

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

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