Sacituzumab Govitecan + Pembrolizumab for Triple Negative Breast Cancer

(ASCENT-05 Trial)

Recruiting at 252 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must not be taking: Endocrine therapy, HER2-directed agents

Disqualifiers: Stage IV breast cancer, BRCA mutations, 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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

1514 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug combination is effective and safe for individuals with triple-negative breast cancer that persists after surgery and initial treatments. Participants will receive either the experimental treatment of sacituzumab govitecan (Trodelvy) with pembrolizumab (KEYTRUDA) or a treatment chosen by the doctor, which could be pembrolizumab alone or with capecitabine (Xeloda). The trial aims to determine which option better prevents cancer from returning. Individuals whose triple-negative breast cancer was not fully removed by previous treatments and surgery might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on treatments like stimulatory or coinhibitory T-cell receptor agents, HER2-directed agents, endocrine therapy agents, topoisomerase 1 inhibitors, or antibody-drug conjugates containing a topoisomerase inhibitor, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of sacituzumab govitecan and pembrolizumab does not present any new safety concerns. Earlier studies did not reveal unexpected side effects, and participants tolerated it well. Studies also indicate that this combination can improve outcomes, such as delaying the progression of triple-negative breast cancer.

Pembrolizumab is already used for other health issues, which provides some confidence in its safety. Researchers are still studying sacituzumab govitecan with pembrolizumab for safety and effectiveness.

For those considering joining a trial, these findings suggest that the treatment is generally well-tolerated. However, discussing potential risks with a healthcare provider is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sacituzumab govitecan-hziy (SG) combined with pembrolizumab for treating triple-negative breast cancer because it offers a novel approach compared to existing therapies. While traditional treatments like chemotherapy attack rapidly dividing cells, SG uses an innovative mechanism by combining an antibody with a chemotherapy agent, specifically targeting cancer cells and delivering the drug directly to them. This targeted delivery can potentially reduce side effects and improve effectiveness. Additionally, pembrolizumab, an immune checkpoint inhibitor, works by enhancing the body’s immune response against cancer cells, which is different from typical chemotherapy's direct attack on cancer cells. Together, this combination has the potential to provide a more effective and precise treatment option for patients.

What evidence suggests that this trial's treatments could be effective for triple negative breast cancer?

Research has shown that combining sacituzumab govitecan with pembrolizumab can help treat triple-negative breast cancer. In this trial, some participants will receive this combination, which reduced the risk of the cancer worsening or causing death by 35% compared to pembrolizumab with standard chemotherapy. This suggests it might be more effective at slowing the cancer's progression. Another study showed early signs that it could help patients live longer. These findings make the treatment promising for those with this difficult-to-treat cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for adults over 18 with triple negative breast cancer that remains after pre-surgery treatment and surgery. They must have completed any needed radiotherapy, be in good physical condition (ECOG 0-1), and have proper organ function. Excluded are those with recurrent or stage IV cancer, prior treatments with certain drugs, known BRCA mutations, recent serious heart issues, severe infections, or previous immunotherapy.

Inclusion Criteria

My organs are functioning well.

I have completed radiotherapy and recovered before starting this study.

I am fully active or can carry out light work.

Exclusion Criteria

I am currently being treated for a serious infection.

I have not been treated with specific immune system drugs or HER2-targeted therapies before.

I haven't had a heart attack or severe heart issues in the last 6 months and my heart pumps well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sacituzumab govitecan-hziy and pembrolizumab or treatment of physician's choice for up to 8 cycles

24 weeks

8 cycles of 21 days each

Follow-up

Participants are monitored for recurrence-free survival, invasive disease-free survival, overall survival, and quality of life

Up to 96 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Pembrolizumab
• Sacituzumab govitecan-hziy (SG)

Trial Overview

The study compares the effectiveness of sacituzumab govitecan-hziy (SG) combined with pembrolizumab to the physician's choice of treatment post-surgery for patients with residual triple negative breast cancer. The physician's choice may include pembrolizumab alone or combined with capecitabine.

How Is the Trial Designed?

Group I: Sacituzumab govitecan-hziy (SG) + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive SG 10 mg/kg intravenously on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles. Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.

Group II: Treatment of Physician's Choice (TPC): Pembrolizumab or Pembrolizumab + Capecitabine Active Control 2 Interventions

Participants will receive one of the following TPC regimens determined prior to randomization: * Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles OR * Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles and capecitabine 1000 mg/m\^2 orally twice daily on Days 1 through 14 of 21-day cycles for 8 cycles. Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• 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

NSABP Foundation Inc

Collaborator

Trials

89

Recruited

140,000+

GBG Forschungs GmbH

Collaborator

Trials

50

Recruited

47,500+

Alliance Foundation Trials, LLC.

Collaborator

Trials

25

Recruited

27,200+

Published Research Related to This Trial

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 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 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 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 (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 (SG) has been approved in the EU for treating adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have undergone at least two prior systemic therapies, showing significant improvements in progression-free survival (4.8 months vs. 1.7 months) and overall survival (11.8 months vs. 6.9 months) compared to treatment of physician's choice.

The most common side effects of SG include diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation, and vomiting, occurring in more than 30% of patients, indicating that while SG is effective, it also has notable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. Michaleas, S., Moreno Oliver, A., Mueller-Berghaus, J., et al.[2022]

Citations

1.

merck.com

merck.com/news/keytruda-pembrolizumab-plus-trodelvy-sacituzumab-govitecan-hziy-reduced-risk-of-disease-progression-or-death-by-35-versus-keytruda-plus-chemotherapy-in-first-line-pd-l1-metastatic-tri/

KEYTRUDA® (pembrolizumab) Plus Trodelvy® ...

KEYTRUDA® (pembrolizumab) Plus Trodelvy® (sacituzumab govitecan-hziy) Reduced Risk of Disease Progression or Death by 35% Versus KEYTRUDA Plus Chemotherapy in ...

2.

gilead.com

gilead.com/news/news-details/2025/trodelvy-plus-keytruda-demonstrates-a-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-previously-untreated-pd-l1-metastatic-trip

Trodelvy® Plus Keytruda® Demonstrates a Statistically ...

Trodelvy Plus Keytruda shows an early trend in improvement for overall survival versus standard of care in patients with previously untreated PD-L1+ (CPS ≥10) ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05382286

NCT05382286 | Study of Sacituzumab Govitecan-hziy and ...

The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) and pembrolizumab versus ...

4.

esmoopen.com

esmoopen.com/article/S2059-7029(25)01177-9/fulltext

Effectiveness of sacituzumab govitecan and management ...

We describe the real-world effectiveness of SG as 2L+ mTNBC treatment and the proportion of patients with neutropenia and its management.

5.

gileadclinicaltrials.com

gileadclinicaltrials.com/study?id=GS-US-595-6184

Study of Sacituzumab Govitecan-hziy and Pembrolizumab ...

The goal of this study is to find out if the experimental product, sacituzumab govitecan-hziy (SG) in combination with pembrolizumab given after ...

6.

targetedonc.com

targetedonc.com/view/sacituzumab-govitecan-plus-pembrolizumab-improves-pfs-in-pd-l1-tnbc

Sacituzumab Govitecan Plus Pembrolizumab Improves ...

ASCENT-04 data showed sacituzumab govitecan plus pembrolizumab improved progression-free survival in PD-L1+ metastatic triple-negative breast ...

7.

cancernetwork.com

cancernetwork.com/view/sacituzumab-govitecan-combo-shows-pathologic-responses-in-early-stage-tnbc

Sacituzumab Govitecan Combo Shows Pathologic ...

Data from the NeoSTAR trial showed no new safety signals with sacituzumab govitecan plus pembrolizumab for early-stage triple-negative breast cancer.