Sacituzumab Govitecan +/- Pembrolizumab for Breast Cancer

Not currently recruiting at 8 trial locations

Overseen By Ana Garrido-Castro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ana C Garrido-Castro

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

Disqualifiers: Untreated brain metastases, Autoimmune disease, HIV, Hepatitis B/C, 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: 1

Duration: 24 weeks or longer

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of two treatments, Sacituzumab Govitecan (a targeted therapy) and Pembrolizumab (an immunotherapy), for individuals with metastatic HR+/HER2- breast cancer. The researchers aim to assess how these drugs perform both individually and in combination in managing the disease. Participants should have breast cancer that has spread and not responded to previous hormone treatments. This trial may suit those with advanced breast cancer that hasn't improved with prior therapies and are open to exploring new treatment options. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must stop any strong UGT1A1 inhibitors or inducers and discontinue any biologic, targeted, or chemotherapy treatments at least 14 days before starting the study treatment. You can continue bisphosphonates or RANK ligand inhibitors if needed.

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

Research has shown that sacituzumab govitecan, a treatment for certain types of breast cancer, has been used safely in past studies. The FDA has already approved it for other breast cancers, indicating it is generally well-tolerated. Common side effects include nausea and low blood cell counts, but medical help can manage these.

Pembrolizumab, often used in cancer treatments, has also proven safe for many patients in previous studies. Its FDA approval for various cancers reflects confidence in its safety. Some people might experience side effects like tiredness or a rash, but these are usually mild and manageable by healthcare providers.

When used together, sacituzumab govitecan and pembrolizumab have shown safety in studies, with side effects similar to when used separately. This combination has reduced the risk of disease progression in some cases, suggesting it can be an effective and safe option for patients. Always consult a healthcare provider to understand the potential risks and benefits for specific situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sacituzumab Govitecan and Pembrolizumab for breast cancer because they bring new strategies to the table. Sacituzumab Govitecan targets the TROP-2 protein found in many breast cancer cells and delivers a potent chemotherapy directly to them, which can minimize harm to healthy cells. Pembrolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells. This combination could offer a powerful one-two punch by both directly attacking cancer cells and boosting the body's natural defenses, setting it apart from standard chemotherapy or hormonal therapies.

What evidence suggests that this trial's treatments could be effective for metastatic HR+/HER2- breast cancer?

Research has shown that sacituzumab govitecan can significantly improve outcomes for individuals with metastatic hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer. It extends the time patients live without their cancer worsening compared to standard chemotherapy. In this trial, some participants will receive sacituzumab govitecan alone, while others will receive it with pembrolizumab, a treatment that enhances the immune system's ability to fight cancer. When combined with pembrolizumab, this regimen reduced the risk of cancer progression or death by 35% compared to pembrolizumab with chemotherapy. These findings suggest that sacituzumab govitecan, either alone or with pembrolizumab, can effectively treat this type of breast cancer. ^{5 6 7 8 9}

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 advanced or metastatic HR+/HER2- breast cancer who have seen their disease progress after hormone therapy. They should have measurable disease, be able to undergo biopsies, and not exceed one prior chemo treatment for metastasis. Participants need normal organ function and must agree to contraception if applicable.

Inclusion Criteria

My cancer worsened during or after hormone therapy, and I am now considered suitable for chemotherapy.

My breast cancer is advanced and cannot be removed by surgery.

I agree to have two biopsies: one now and another 3-6 weeks after starting treatment.

Exclusion Criteria

I am on long-term steroids or other drugs that weaken my immune system.

You had an allergic reaction to the ingredients in pembrolizumab or sacituzumab govitecan therapy before.

Participants who are breast-feeding are not eligible for enrollment

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. Each cycle is 21 days, with Sacituzumab Govitecan administered twice per cycle and Pembrolizumab once per cycle.

24 weeks or longer

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations and follow-up visits.

3 years

Regular follow-up visits

Second Course Phase

Participants who have attained a confirmed complete response and meet protocol-specified conditions may be eligible for additional treatment if they progress after stopping study treatment.

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Govitecan

Trial Overview

The study tests the effectiveness of Sacituzumab Govitecan alone or combined with Pembrolizumab in treating certain breast cancers. It assesses safety, how well tumors respond, and compares outcomes between the two approaches.

How Is the Trial Designed?

Group I: Sacituzumab Govitecan + Pembrolizumab Experimental Treatment 2 Interventions

The research study procedures include: screening for eligibility, research blood collections, at least two research biopsies, paired research stool collections, and study treatment including evaluations and follow up visits. Each Cycle =21 Days * Sacituzumab Govitecan (iv) fixed dose, administered twice per cycle * Pembrolizumab (iv) fixed dose administered once per cycle

Group II: Sacituzumab Govitecan Experimental Treatment 1 Intervention

The research study procedures include: screening for eligibility, research blood collections, at least two research biopsies, paired research stool collections, and study treatment including evaluations and follow up visits. \- Sacituzumab Govitecan (iv) fixed dose, administered twice per cycle

Group III: Retreatment Experimental Treatment 2 Interventions

Participants who have attained a confirmed complete response (CR) who have been treated for at least 24 weeks on protocol therapy and had at least three cycles (with pembrolizumab and sacituzumab govitecan (Arm A) or sacituzumab govitecan alone (Arm B)) beyond the date when the initial CR was declared may be eligible for additional sacituzumab govitecan and/or pembrolizumab therapy if they progress after stopping study treatment. This retreatment is termed the Second Course Phase of this study and is only available if the study remains open and the subject meets protocol-specified 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?

Ana C Garrido-Castro

Lead Sponsor

Trials

1

Recruited

110+

Ana C Garrido-Castro, MD

Lead Sponsor

Trials

2

Recruited

470+

Sara Tolaney

Lead Sponsor

Trials

1

Recruited

110+

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

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

Published Research Related to This Trial

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) in patients with endocrine-resistant HR+/HER2- metastatic breast cancer, showing a 34% reduction in the risk of progression or death compared to standard chemotherapy.

The safety profile of SG was manageable, with notable grade ≥ 3 adverse events including neutropenia and diarrhea, but it still represents a promising treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. Rugo, HS., Bardia, A., Marmé, F., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

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 (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]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2511734

Sacituzumab Govitecan in Untreated, Advanced Triple- ...

Here, we report the primary results from the ASCENT-03 trial of sacituzumab govitecan as compared with chemotherapy for the first-line treatment ...

2.

gilead.com

gilead.com/news/news-details/2025/ascent-03-trodelvy-demonstrates-highly-statistically-significant--clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-first-line-metastatic-triple-negative-breast

ASCENT 03 Trodelvy Demonstrates Highly Statistically ...

The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12173046/

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.

nature.com

nature.com/articles/s41591-024-03269-z

Sacituzumab govitecan in HR+HER2− metastatic breast ...

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in hormone receptor-positive ...

5.

trodelvy.com

trodelvy.com/patient/mtnbc/clinical-trial-results

Clinical trial results in mTNBC

What is TRODELVY? TRODELVY® (sacituzumab govitecan-hziy) is a prescription medicine used to treat adults with triple-negative breast cancer (negative for ...

6.

trodelvyhcp.com

trodelvyhcp.com/mtnbc/safety/safety

TRODELVY® (sacituzumab govitecan-hziy) Safety Profile

TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2021/761115s009lbl.pdf

sacituzumab govitecan-hziy - accessdata.fda.gov

TRODELVY is indicated for the treatment of adult patients with unresectable locally advanced or metastatic triple- negative breast cancer (mTNBC) who have ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S096097762400184X

Safety profile of sacituzumab govitecan in patients with ...

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

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01631552

Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults ...

The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day ...