Sacituzumab Govitecan for Breast Cancer

(ASCENT-07 Trial)

Recruiting at 288 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must be taking: Antiretroviral therapy

Must not be taking: Investigational drugs, Topoisomerase I inhibitors

Disqualifiers: Active second malignancy, Serious infection, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 21-28 days per cycle, repeated until progression or unacceptable toxicity

654 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to see if sacituzumab govitecan-hziy (SG) can improve life spans of people with HR+/HER2- metastatic breast cancer and their tumor does not grow or spread when compared to currently available standard treatments, such as paclitaxel, nab-paclitaxel or capecitabine. The primary objective is to compare the effect of SG relative to the treatment of physician's choice (TPC) on progression-free survival (PFS).

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

The trial information does not specify if you need to stop taking your current medications. However, you cannot be enrolled in another clinical study or use investigational drugs close to the trial start date.

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, with a study reporting a 33.3% response rate and a median duration of response of 7.7 months. It was approved by the FDA based on these results, indicating it can help patients who have already tried other 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, skin rash, decreased appetite, and abdominal pain. These side effects occurred in 25% or more of patients. ^{1 2 3 5 6}

What makes the drug Sacituzumab Govitecan unique for treating breast cancer?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that specifically targets a protein called Trop-2 on cancer cells, delivering a chemotherapy agent directly to the tumor, which can lead to higher concentrations of the drug in the cancer cells and potentially better outcomes for patients with metastatic triple-negative breast cancer who have already tried other treatments. ^{1 2 3 7 8}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with HR+/HER2- metastatic breast cancer who've had disease progression despite endocrine therapy. They must have a sample of tumor tissue available, not be candidates for further endocrine treatment, and have adequate organ function. HIV-positive participants need controlled infection on ART. Participants must agree to use contraception and should not be eligible for curative intent therapy or have received certain prior treatments.

Inclusion Criteria

My breast cancer is hormone receptor positive and has spread, confirmed by a recent biopsy.

My organs are functioning well.

My cancer returned within 24 months while on hormone therapy, counting as one treatment line.

Exclusion Criteria

I haven't taken any experimental estrogen-blocking drugs in the last 14 days.

I am HIV positive with a history of Kaposi sarcoma or Multicentric Castleman Disease.

My breast cancer is advanced but considered treatable with the intent to cure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sacituzumab govitecan-hziy (SG) or treatment of physician's choice (TPC) based on randomization

21-28 days per cycle, repeated until progression or unacceptable toxicity

Visits on Days 1, 8, and 15 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 60 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Capecitabine
• Nab-paclitaxel
• Paclitaxel
• Sacituzumab Govitecan-hziy

Trial Overview The study tests if Sacituzumab Govitecan (SG) extends the time without cancer growth in patients with HR+/HER2- metastatic breast cancer compared to standard treatments like Paclitaxel, Nab-paclitaxel, or Capecitabine. It measures how long patients live without their disease getting worse.

Participant Groups

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

Participants will receive SG at a dose of 10 mg/kg infusion on Days 1 and 8 of a 21-day cycle.

Group II: Treatment of Physician's Choice (TPC) Active Control 3 Interventions

Participants will receive TPC determined prior to randomization to 1 of the 3 allowed regimens: * paclitaxel 80 mg/m\^2 over 1 hour (± 10 minutes) on Days 1, 8, and 15 of a 28-day cycle. * nab-Paclitaxel 100 mg/m\^2 over 30 minutes (± 10 minutes) on Days 1, 8, and 15 of a 28-day cycle. * capecitabine at 1000-1250 mg/m\^2 twice daily for 2 weeks followed by a 1-week rest period of a 21-day cycle.

Sacituzumab Govitecan-hziy 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
• Metastatic urothelial cancer
• Metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative 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?

Gilead Sciences

Lead 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]

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 (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-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]

Sacituzumab govitecan (SG) demonstrated effectiveness in treating relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC), with a median overall survival of 12.9 months and an objective response rate of 34% based on an analysis of 412 patients across three trials.

The treatment was associated with significant adverse effects, particularly myelosuppression, with 46% of patients experiencing grade ≥3 neutropenia, and there were four treatment-related deaths reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. Cheng, SX., Chen, QC., Lin, GH., 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]

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

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

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

Sacituzumab Govitecan: First Approval. [2021]

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

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

5. 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]

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

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

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

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. [2023]

8. 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]