Sacituzumab Govitecan for Triple-Negative Breast Cancer

(ASCENT-03 Trial)

Recruiting at378 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Gilead Sciences

Must not be taking: Topoisomerase inhibitors

Disqualifiers: Pregnancy, Active infection, Second malignancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called sacituzumab govitecan-hziy, which targets and kills cancer cells. It focuses on patients with advanced triple-negative breast cancer who have limited treatment options. The drug works by attaching to cancer cells and releasing a substance that kills them. Sacituzumab govitecan-hziy is an FDA-approved treatment for metastatic triple-negative breast cancer, especially for patients who have already tried other treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic anticancer treatment, you must have completed it at least 6 months before joining the trial.

What data supports the effectiveness of the drug Sacituzumab Govitecan-hziy for treating triple-negative breast cancer?

Sacituzumab Govitecan-hziy has shown effectiveness in treating metastatic triple-negative breast cancer, with a study reporting a 33.3% response rate among patients who had already tried at least two other treatments. The drug helps deliver high concentrations of a cancer-fighting substance directly to tumors, and it has been approved by the FDA based on these results. ^{1 2 3 4 5}

What safety data exists for Sacituzumab Govitecan in humans?

Sacituzumab Govitecan has been studied 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. ^{1 2 3 5 6}

What makes the drug sacituzumab govitecan unique for treating triple-negative 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 (SN-38) directly to the tumor, which can improve effectiveness and reduce side effects compared to standard chemotherapy. ^{1 3 4 5 7}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with previously untreated advanced or metastatic triple-negative breast cancer that doesn't show PD-L1, or those who've had anti-PD-(L)1 treatment if their tumors are PD-L1 positive. Participants must have good organ function, not be pregnant, and agree to use contraception. They can't join if they've had recent cancer treatments, active infections requiring antibiotics, another active cancer, or haven’t recovered from past treatment side effects.

Inclusion Criteria

My breast cancer was already at an advanced stage when first diagnosed.

I have triple-negative breast cancer that has not been treated and cannot be removed by surgery.

I agree to use birth control as required by the study.

Exclusion Criteria

Positive serum pregnancy test or women who are lactating

May not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Individuals participating in observational studies are eligible

I am HIV positive and have had Kaposi sarcoma or Multicentric Castleman Disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Sacituzumab Govitecan-hziy or Treatment of Physician's Choice in cycles

21-28 days per cycle, ongoing 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 57 months

Treatment Details

Interventions

• Sacituzumab Govitecan-hziy (Monoclonal Antibodies)

Trial Overview The study compares Sacituzumab Govitecan-hziy (SG), a new drug for breast cancer, against the physician's choice of standard treatments like Paclitaxel or nab-Paclitaxel combined with Gemcitabine and Carboplatin. The main goal is to see which option keeps the cancer from worsening longer (progression-free survival).

Participant Groups

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

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

Group II: Treatment of Physician's Choice (TPC) Active Control 4 Interventions

Participants will receive TPC determined prior to randomization from 1 of the 3 allowed regimens: * Paclitaxel 90 mg/m\^2 on Days 1, 8, and 15 of a 28-day cycle * Nab-paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of a 28-day cycle * Gemcitabine 1000 mg/m\^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of a 21-day cycle

Sacituzumab Govitecan-hziy is already approved in Canada for the following indications:

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]

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]

In a study of 43 patients with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan, the median overall survival was 13.1 months, indicating its effectiveness in a real-world setting.

Common adverse events included alopecia, diarrhea, and neutropenia, with 27.9% of patients experiencing Grade 3 neutropenia, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. Reinisch, M., Bruzas, S., Spoenlein, J., et al.[2023]

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 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 received full FDA approval after a phase III trial showed it significantly improves progression-free survival in patients with metastatic triple-negative breast cancer, achieving a median of 5.7 months compared to just 1.7 months with standard chemotherapy.

This treatment is an antibody-drug conjugate that targets the Trop-2 receptor and delivers the active metabolite of irinotecan, SN-38, directly to cancer cells, making it a promising option for patients who have already undergone at least two prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. Fleming, PJ., Karpio, S., Lombardo, N.[2021]

In a phase 3 trial involving 468 patients with metastatic triple-negative breast cancer, sacituzumab govitecan significantly improved progression-free survival (5.6 months) and overall survival (12.1 months) compared to standard chemotherapy (1.7 months and 6.7 months, respectively).

While sacituzumab govitecan showed better efficacy, it was associated with higher rates of certain adverse events, such as neutropenia (51% vs. 33% with chemotherapy) and diarrhea (10% vs. <1%), but no deaths were linked to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. Bardia, A., Hurvitz, SA., Tolaney, SM., 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

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

3. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. [2023]

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

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

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

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. [2021]

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

Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. [2022]