Sacituzumab Govitecan + Pembrolizumab for Triple Negative Breast Cancer

Recruiting at 11 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 research study involves testing the safety and efficacy of an investigational intervention for patients with triple-negative breast cancer (TNBC) that has spread, or metastasized, to other parts the body and is PD-L1-negative. The names of the study interventions involved in this study are: * Sacituzumab govitecan (Trodelvy™;IMMU-132) * Pembrolizumab (Keytruda®; MK-3475)

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.

What is known about the safety of Sacituzumab Govitecan and Pembrolizumab for human use?

Sacituzumab Govitecan has been studied in patients with advanced solid tumors, showing common side effects like nausea, fatigue, and diarrhea, but is generally well tolerated. Pembrolizumab, also known as KEYTRUDA, is widely used in various cancers and has a known safety profile, but specific safety data for the combination with Sacituzumab Govitecan in triple-negative breast cancer is not detailed in the provided research. ^{1 2 3 4 5}

How is the drug Sacituzumab Govitecan + Pembrolizumab unique for treating triple-negative breast cancer?

This drug combination is unique because Sacituzumab Govitecan is an antibody-drug conjugate that targets a specific protein (Trop-2) on cancer cells and delivers a potent chemotherapy agent (SN-38) directly to the tumor, while Pembrolizumab is an immunotherapy that helps the immune system attack cancer cells. This combination offers a novel approach by combining targeted therapy with immunotherapy for treating triple-negative breast cancer. ^{1 2 4 5 6}

What data supports the effectiveness of the drug Sacituzumab Govitecan for treating triple-negative 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 response duration of 7.7 months. It is well tolerated and has been approved by the FDA for patients who have tried at least two other treatments. ^{1 2 3 4 7}

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 (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 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 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-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, 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 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]

Citations

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

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

2. 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]

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

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

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

ADC Could Benefit Some with Breast Cancer. [2020]

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