Sacituzumab Govitecan + Pembrolizumab for Triple-Negative Breast Cancer

(ASCENT-04 Trial)

Not currently recruiting at 599 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must not be taking: Topoisomerase inhibitors

Disqualifiers: Pregnancy, Active infection, Autoimmune, 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

Compensation: Varies

Number of Visits: 1

Duration: Up to 35 cycles of 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with triple-negative breast cancer (TNBC) that has spread or cannot be surgically removed. The aim is to determine if combining sacituzumab govitecan-hziy, a targeted therapy, with pembrolizumab, an immunotherapy, controls the cancer more effectively than the standard treatment, which includes pembrolizumab and a doctor-chosen therapy. Participants should have TNBC that has not been treated for advanced stages, and their tumors must express a specific protein (PD-L1). This trial may suit those with TNBC who have not yet received treatment for advanced disease and whose previous cancer treatment concluded at least six months ago. As a Phase 3 trial, this study serves as the final step before potential FDA approval, offering participants an opportunity to contribute to advancing cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received systemic anticancer treatment (except endocrine therapy) within the last 6 months or radiation therapy within 2 weeks before joining the trial.

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

Research has shown that sacituzumab govitecan, a targeted cancer treatment, is approved for a specific type of advanced breast cancer. Studies have found that combining sacituzumab govitecan with pembrolizumab, another cancer treatment, significantly extended the time patients lived without their cancer worsening. Importantly, this combination revealed no new safety issues.

Pembrolizumab is a well-known treatment for many cancer types. It is generally well-tolerated, with its safety well-documented.

In summary, both sacituzumab govitecan and pembrolizumab have been widely studied. Recent studies report no unexpected side effects, confirming their safety for use in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine pembrolizumab, an immunotherapy, with sacituzumab govitecan-hziy, a targeted therapy, offering a potentially powerful duo for tackling triple-negative breast cancer. Pembrolizumab works by revving up the body's immune system to attack cancer cells, while sacituzumab govitecan-hziy delivers chemotherapy directly to the cancer, minimizing damage to healthy cells. This combination targets cancer cells more precisely and could enhance treatment effectiveness compared to standard chemotherapy options like paclitaxel or gemcitabine with carboplatin.

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

Research shows that combining the drugs sacituzumab govitecan and pembrolizumab may be promising for treating triple-negative breast cancer. In this trial, one group of participants will receive this combination. Studies have found that it significantly improves the time patients live without their cancer worsening, compared to standard chemotherapy with pembrolizumab. Specifically, it reduced the risk of disease progression or death by 35%. This combination also offers long-lasting benefits without new safety concerns. These findings suggest that this treatment could effectively manage triple-negative breast 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 with advanced triple-negative breast cancer that hasn't been treated yet and tests positive for PD-L1. They must have measurable disease, agree to use contraception if of childbearing potential, and have an ECOG performance status of 0 or 1. Those with HIV can join if it's well-controlled on ART.

Inclusion Criteria

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

I am fully active or restricted in physically strenuous activity but can do light work.

I finished my breast cancer treatment over 6 months ago and now have a recurrence.

Exclusion Criteria

I have been treated with drugs targeting immune cells before.

Positive serum pregnancy test or women who are lactating

I have an active hepatitis B or C infection.

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 and pembrolizumab

Up to 35 cycles of 21-day cycles

Visits on Days 1 and 8 of each cycle

Follow-up

Participants are monitored for progression-free survival and other outcomes

Up to approximately 53 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Govitecan-hziy

Trial Overview The study compares the effectiveness of Sacituzumab Govitecan-hziy (SG) combined with Pembrolizumab versus a physician-chosen treatment paired with Pembrolizumab in extending the time patients live without their cancer getting worse.

How Is the Trial Designed?

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

Participants will receive SG 10 mg/kg on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg on Day 1 of 21-day cycles Pembrolizumab will be administered for a maximum of 35 cycles.

Group II: Pembrolizumab + Treatment of Physician's Choice (TPC) Active Control 5 Interventions

Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens: * Paclitaxel 90 mg/m\^2 on Days 1, 8, and 15 of 28-day cycles * nab-Paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of 28-day cycles * Gemcitabine 1000 mg/m\^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

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, an antibody-drug conjugate, has shown activity against difficult-to-treat metastatic triple-negative breast cancer in a phase I/II trial.

A phase III trial is currently being conducted to evaluate the safety and efficacy of sacituzumab govitecan compared to standard chemotherapy, which will provide further insights into its potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Could Benefit Some with Breast Cancer. [2020]

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]

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]

Citations

1. 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) ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2511734

Sacituzumab Govitecan in Untreated, Advanced Triple- ... Sacituzumab govitecan monotherapy resulted in significantly longer progression-free survival than chemotherapy among patients who had undergone ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA109

Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs ... SG + pembro led to a statistically significant and clinically meaningful improvement in PFS vs chemo + pembro with durable responses, no new safety concerns ...

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05675579

NCT05675579 | A Phase II Study of Neoadjuvant ... To learn if sacituzumab govitecan and pembrolizumab, when given before surgery, can help to control early-stage triple negative breast cancer.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40361516/

The Clinical Outcomes and Safety of Sacituzumab ... Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting Trop-2, approved for use in metastatic triple-negative breast cancer (mTNBC)

7. dana-farber.org dana-farber.org/newsroom/news-releases/2025/adc-improves-outcomes-for-patients-with-advanced-triple-negative-breast-cancer-who-are-ineligible-for-immune-checkpoint-inhibitors

ADC Improves Outcomes for Patients with Advanced Triple ... "The data from ASCENT-03 are very compelling and support sacituzumab govitecan as a potential new standard of care for patients with previously ...