Sacituzumab Govitecan + Pembrolizumab for Breast Cancer

Overseen By Clinton Yam, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Pembrolizumab

Must not be taking: Immunosuppressants

Disqualifiers: Stage IV cancer, Autoimmune disease, 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: Unknown

Duration: Approximately 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two drugs, sacituzumab govitecan and pembrolizumab, in controlling early-stage triple-negative breast cancer that hasn't responded to other treatments. The goal is to determine if these drugs can shrink the tumor before surgery. Suitable candidates for this trial have early-stage breast cancer that hasn't reduced in size after initial treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that the combination of sacituzumab govitecan and pembrolizumab has been well-tolerated in clinical trials for breast cancer. These studies have demonstrated that this combination significantly helps control the disease in patients with triple-negative breast cancer. Researchers compared this combination to other treatments like chemotherapy and found it lowered the risk of disease progression or death.

While specific details on side effects aren't available, testing this combination in multiple trials suggests it is considered safe enough for further study. Since both drugs are already used in treatments, their history provides some reassurance about their safety when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sacituzumab Govitecan combined with Pembrolizumab for breast cancer because it takes a novel dual-action approach. Sacituzumab Govitecan is an antibody-drug conjugate that specifically targets cancer cells and delivers a chemotherapy agent directly to them, reducing harm to healthy cells. Meanwhile, Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells more effectively. Unlike traditional breast cancer treatments like hormone therapies or standard chemotherapies, this combination aims to enhance effectiveness by both directly killing cancer cells and boosting the body's own defenses against them.

What evidence suggests that sacituzumab govitecan and pembrolizumab might be effective for early-stage triple negative breast cancer?

Research shows that combining sacituzumab govitecan with pembrolizumab yields promising results for certain breast cancers. In this trial, participants will receive this combination, which earlier studies found helped patients with advanced cancer live longer without disease progression. It outperformed traditional chemotherapy with pembrolizumab alone, offering lasting benefits. Importantly, researchers found no new safety issues, indicating it is as safe as current treatments. These findings suggest this combination could be effective for early-stage triple-negative breast cancer, especially for those not responding to other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinton Yam, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with early-stage triple-negative breast cancer that hasn't improved with initial treatment. Participants must have specific tumor characteristics, agree to biopsies, and use effective birth control if of childbearing potential. Exclusions include prior treatments for the current cancer, certain health conditions, pregnancy, or active infections.

Inclusion Criteria

My breast cancer is in the early stages and has been confirmed by a lab test.

My cancer is either not responsive to hormones or barely responsive, and does not have too much HER2.

My tumor size hasn’t changed or has grown after starting the KN-522 treatment.

Exclusion Criteria

I have not had any live vaccines in the last 30 days.

I have an autoimmune disease needing treatment or need medicine to suppress my immune system.

I have HIV or hepatitis but meet the specific conditions for treatment eligibility.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan and pembrolizumab therapy. Sacituzumab govitecan is administered on Days 1 and 8 of Cycles 1-4, and pembrolizumab is administered on Days 1, 8, and 15 of each cycle.

Approximately 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of pathological complete response and survival rates.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Govitecan

Trial Overview The study tests whether sacituzumab govitecan and pembrolizumab given before surgery can manage early-stage triple-negative breast cancer resistant to initial therapy. It's a phase II trial focusing on patients who didn't respond well to first-line immunochemotherapy.

How Is the Trial Designed?

Group I: Sacituzumab Govitecan and Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive drug on Days 1 and 8 of Cycles 1-4, Participants will receive sacituzumab govitecan by vein. Participants will receive drug on Days 1, 8, and 15 of each cycle, Participants will receive pembrolizumab by vein.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

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 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]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

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]

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]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

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 (SG) demonstrated effectiveness in treating relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC), with a median overall survival of 12.9 months and an objective response rate of 34% based on an analysis of 412 patients across three trials.

The treatment was associated with significant adverse effects, particularly myelosuppression, with 46% of patients experiencing grade ≥3 neutropenia, and there were four treatment-related deaths reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. Cheng, SX., Chen, QC., Lin, GH., et al.[2023]

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]

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]

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 (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]

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 ... It has now demonstrated improved outcomes in three Phase 3 breast cancer trials and is being studied in several ongoing clinical trials ...

2. 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 ...

3. 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® ... These data from the pivotal Phase 3 ASCENT-04/KEYNOTE-D19 study will be presented today as a late-breaking oral presentation at the 2025 American Society of ...

4. 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.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04468061?term=Sacituzumab&rank=2

Sacituzumab Govitecan +/- Pembrolizumab in Metastatic ... This research study involves testing the safety and efficacy of an investigational intervention for patients with triple-negative breast cancer (TNBC) that ...

7. onclive.com onclive.com/view/sacituzumab-govitecan-plus-pembrolizumab-improves-pfs-in-pd-l1-positive-mtnbc

Sacituzumab Govitecan Plus Pembrolizumab Improves ... The combination of sacituzumab govitecan and pembrolizumab improved PFS vs pembrolizumab plus chemotherapy in PD-L1–positive mTNBC.

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

Sacituzumab Govitecan Plus Pembrolizumab Improves ... The combination of sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) significantly improved progression-free survival (PFS)