Sacituzumab Govitecan + Pembrolizumab for Triple Negative Breast Cancer

Recruiting at 14 trial locations

Overseen By Ana C Garrido-Castro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Anti-PD-1, PD-L1, PD-L2

Disqualifiers: Autoimmune disease, HIV, Hepatitis, 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

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

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks or longer

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments: sacituzumab govitecan (an antibody-drug conjugate) and pembrolizumab (an immunotherapy drug) for individuals with triple-negative breast cancer (TNBC) that has spread and is PD-L1-negative. The goal is to determine if these drugs can safely and effectively treat this cancer. Individuals diagnosed with this type of cancer, who have not received prior treatment in the metastatic setting, and whose tumors lack specific proteins like PD-L1, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received any prior chemotherapy or biologic therapy for metastatic breast cancer within 28 days before starting the study treatment. You can continue or start bisphosphonates or RANK ligand inhibitors if needed.

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

Earlier studies have linked sacituzumab govitecan to a high rate of side effects in breast cancer patients. Neutropenia, a common and potentially serious side effect, involves a low count of white blood cells that fight infections. Proper care can often manage these side effects.

Research shows that when sacituzumab govitecan is combined with pembrolizumab, the side effects remain similar to those seen when each drug is used alone.

This trial is in phase 2, indicating that while earlier studies have shown some safety, researchers are still carefully studying its effects to ensure it is safe for more people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sacituzumab Govitecan combined with Pembrolizumab for treating triple-negative breast cancer due to its unique dual approach. Unlike traditional chemotherapy, which broadly attacks fast-growing cells, Sacituzumab Govitecan is an antibody-drug conjugate that specifically targets cancer cells with the active ingredient SN-38, minimizing damage to healthy cells. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and destroy cancer cells. This combination offers a targeted and potentially more effective treatment option, making it a promising alternative to existing therapies for this challenging type of breast cancer.

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

Research has shown that sacituzumab govitecan, one of the treatments in this trial, effectively treats metastatic triple-negative breast cancer (TNBC). Studies have found that it reduces the risk of cancer progression or death by 38% compared to standard chemotherapy. Real-world evidence also supports its success in helping patients with advanced TNBC.

In this trial, some participants will receive sacituzumab govitecan alone, while others will receive a combination of sacituzumab govitecan and pembrolizumab. Research indicates that this combination reduces the risk of cancer worsening or leading to death by 35% compared to using pembrolizumab with chemotherapy. These findings highlight the potential of sacituzumab govitecan, both on its own and in combination with other treatments, for managing TNBC. ^{2 4 6 7 8}

Who Is on the Research Team?

Ana C. Garrido-Castro

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with PD-L1-negative metastatic triple-negative breast cancer (TNBC). Participants must have not received treatment for metastasis, be in good physical condition, and have normal organ/marrow function. They should agree to a research biopsy if possible. Pregnant women or those breastfeeding are excluded, as well as anyone with certain medical conditions or recent treatments that could interfere with the study.

Inclusion Criteria

My cancer can be measured or seen on scans, including if it's only in my bones.

I have had treatment for brain metastases.

I agree to use birth control during and for 3 months after my treatment.

Exclusion Criteria

I haven't had cancer treatment or experimental drugs in the last 4 weeks, except for bisphosphonates or RANK ligand inhibitors.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate

I have not had major surgery in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Sacituzumab Govitecan with or without Pembrolizumab in 21-day cycles

24 weeks or longer

Visits on days 1 and 8 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Regular follow-up visits

Second Course Phase

Participants who achieve CR after at least 24 weeks of treatment may receive additional therapy if they progress

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Govitecan

Trial Overview

The trial tests Sacituzumab Govitecan (Trodelvy) alone or combined with Pembrolizumab (Keytruda) in patients whose TNBC has spread and doesn't respond to PD-L1 targeting therapies. It aims to determine the safety and effectiveness of these drugs in managing advanced TNBC.

How Is the Trial Designed?

Group I: Sacituzumab Govitecan + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive Sacituzumab Govitecan + Pembrolizumab at a pre-determined dose during a 21 day cycle. Sacituzumab Govitecan will be given on days 1 and 8 of the 21 day cycle Pembrolizumab will be given on day 1 of the 21 day cycle.

Group II: Sacituzumab Govitecan Experimental Treatment 1 Intervention

Participants will receive Sacituzumab Govitecan at a pre-determined dose during a 21 day cycle. Sacituzumab Govitecan will be given on days 1 and 8 of a 21-day cycle

Group III: Retreatment Experimental Treatment 2 Interventions

Participants randomized to the combination arm (Sacituzumab Govitecan + Pembrolizumab) who stop with CR after at least 24 weeks of treatment may be eligible for additional pembrolizumab and/or sacituzumab govitecan therapy if they progress after stopping study treatment. This is termed the Second Course Phase and is only available if the study remains open and the subject meets conditions. .

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

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, 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]

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 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]

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]

Citations

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nejm.org

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Sacituzumab govitecan (SG) is approved for the treatment of metastatic triple-negative breast cancer (mTNBC). We report the real-world clinical effectiveness ...

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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.

4.

gilead.com

gilead.com/news/news-details/2025/trodelvy-reduces-risk-of-disease-progression-or-death-by-38-versus-chemotherapy-as-first-line-therapy-in-patients-with-metastatic-triple-negative-breast-cancer-in-ascent-03-study

Trodelvy Reduces Risk of Disease Progression or Death ...

Trodelvy® Reduces Risk of Disease Progression or Death by 38% Versus Chemotherapy as First-Line Therapy in Patients With Metastatic Triple-Negative Breast ...

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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 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11648803/

Safety profile of sacituzumab govitecan in patients with breast ...

This systematic review and meta-analysis provides extensive data on the safety and management of SG toxicity in BC patients across clinical trials.

7.

trodelvyhcp.com

trodelvyhcp.com/mtnbc/safety/safety

TRODELVY® (sacituzumab govitecan-hziy) Safety Profile

Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer. 2022;8(1):98. 2. TRODELVY ...

8.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13106

Safety profile of sacituzumab govitecan in patients with ...

In this systematic review and meta-analysis, SG was associated with a high incidence of AEs. Neutropenia is a notable and potentially serious adverse event.