Sacituzumab Govitecan + Pembrolizumab for Breast Cancer

(NeoSTAR Trial)

Recruiting at 4 trial locations

Overseen By Laura Spring, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Antiretrovirals

Disqualifiers: Inflammatory breast cancer, Heart disease, HIV, 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: 11

Duration: 12 weeks

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medications, sacituzumab govitecan and pembrolizumab, to evaluate their effectiveness for individuals with triple-negative breast cancer (TNBC). Researchers aim to determine if these drugs, either alone or in combination, can treat this specific cancer that resists some standard treatments. Suitable participants have localized breast cancer diagnosed as triple-negative, meaning their cancer is not driven by certain hormones or proteins. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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

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

Research shows that sacituzumab govitecan (SG) is generally safe, though it can cause some side effects. In earlier studies, common side effects included low white blood cell count, nausea, and diarrhea. These affected more than half of the patients, with low white blood cell count occurring in about 70% of cases, nausea in 62%, and diarrhea in 54%. However, only about 5% of patients stopped treatment due to these side effects.

For the combination of sacituzumab govitecan and pembrolizumab, studies have shown promising safety results. This combination reduced the risk of disease progression or death compared to other treatments. While specific side effects of this combination aren't detailed, the individual drugs have known safety records. Pembrolizumab, for example, is already used to treat other cancers, providing some reassurance about its safety.

This trial is in Phase 2, indicating early evidence of safety, but more data is still needed. The treatment has shown potential, but as with any trial, it's important to weigh possible side effects against potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine Sacituzumab Govitecan and Pembrolizumab, offering a unique approach to treating breast cancer. Unlike traditional chemotherapy, which broadly targets rapidly dividing cells, Sacituzumab Govitecan is an antibody-drug conjugate that specifically targets the Trop-2 protein found on breast cancer cells, delivering chemotherapy directly to the tumor. Pembrolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and fight cancer cells more effectively. This combination aims to enhance treatment precision and effectiveness, providing a more targeted and potentially less toxic alternative to standard therapies.

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

Research has shown that sacituzumab govitecan, which participants in this trial may receive as part of the monotherapy cohort, holds promise for treating triple-negative breast cancer (TNBC). Studies have found it can significantly extend the time patients live without their cancer worsening, compared to traditional chemotherapy. One study showed it lowered the risk of the cancer spreading or causing death by 38% for patients whose cancer had metastasized.

In this trial, another group of participants will receive a combination of sacituzumab govitecan and pembrolizumab. This combination also appears effective, as studies suggest it reduced the risk of the cancer spreading or causing death by 35% compared to using pembrolizumab with chemotherapy. These findings indicate that sacituzumab govitecan, both alone and with pembrolizumab, could be strong options for managing TNBC. ^{3 6 7 8 9}

Who Is on the Research Team?

Laura M Spring, M.D.

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with a specific breast cancer type called triple negative (no ER, PR, HER2 receptors), who haven't been treated yet. They must have a tumor of at least 1 cm without spread to distant parts of the body and be in good health overall. Pregnant or breastfeeding individuals, those with other cancers within 3 years, uncontrolled illnesses, HIV on antiretrovirals or certain heart conditions can't join.

Inclusion Criteria

My cancer has spread to nearby lymph nodes but not beyond.

My breast cancer is not driven by estrogen, progesterone, or HER2.

My blood tests show my organs and bone marrow are working well.

Exclusion Criteria

I do not have uncontrolled heart disease or abnormal heart rhythms.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am not on systemic therapy for another cancer nor have I been in the last 3 years.

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 for up to 12 weeks, with evaluations and follow-up visits

12 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

2 visits (in-person)

Long-term follow-up

Participants are monitored for disease-free survival and overall survival

up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Sacituzumab Govitecan

Trial Overview

The study is testing Sacituzumab Govitecan alone and in combination with Pembrolizumab for treating localized triple negative breast cancer. It aims to see how well these drugs work before any standard treatments like surgery or radiation are given.

How Is the Trial Designed?

Group I: Sacituzumab Govitecan and Pembrolizumab (combination cohort) Experimental Treatment 2 Interventions

\- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Sacituzumab govitecan via iv, predetermined dosage per protocol, IV, 2 days per each 21-day cycle, for 4 cycles. * Pembrolizumab via iv, predetermined dosage per protocol, IV, 1 day per each 21-day cycle, for 4 cycles. * This can be followed by standard chemotherapy at the discretion of treating physician.

Group II: Sacituzumab Govitecan (monotherapy cohort) Experimental Treatment 1 Intervention

\- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Sacituzumab govitecan via iv, predetermined dosage per protocol, IV, 2 days per each 21-day cycle, for 4 cycles. * This can be followed by standard chemotherapy at the discretion of treating physician.

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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Aditya Bardia

Lead Sponsor

Trials

1

Recruited

260+

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

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]

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 (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 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]

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]

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]

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 (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]

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]

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