Sacituzumab Govitecan for Salivary Gland Cancer

Overseen By Renata Ferrarotto, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, others

Disqualifiers: Active CNS disease, uncontrolled infections, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6-12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether sacituzumab govitecan, a cancer treatment, can help manage salivary gland cancer. The study includes two groups: one for individuals with adenoid cystic carcinoma (ACC), a rare type of salivary gland cancer, and another for those with other specific types. Participants should have salivary gland cancer that cannot be treated with surgery or radiation and has shown measurable progression. This trial suits individuals whose daily life is affected by this advanced cancer and who have tried other treatments without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had prior anticancer therapy within 4 weeks before starting the trial treatment.

Is there any evidence suggesting that sacituzumab govitecan is likely to be safe for humans?

Research has shown that sacituzumab govitecan is undergoing testing in several studies to assess its safety and effectiveness. In earlier studies, patients generally tolerated the treatment well. The most common side effects included low blood cell counts, nausea, and tiredness, which can be managed with supportive care. The FDA has also approved sacituzumab govitecan for treating another type of cancer, indicating a known safety record. However, this does not mean it is without side effects. Prospective participants should consult a healthcare provider about potential risks and benefits before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for salivary gland cancer?

Sacituzumab govitecan is unique because it targets a protein called Trop-2, which is often overexpressed in salivary gland cancers, including adenoid cystic carcinoma (ACC) and non-ACC forms. Most traditional treatments for salivary gland cancer involve surgery, radiation, or chemotherapy, which can affect both cancerous and healthy cells. Unlike these standard options, sacituzumab govitecan is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, potentially reducing side effects and improving effectiveness. Researchers are excited about its potential to offer a more targeted approach, which could lead to better outcomes for patients.

What evidence suggests that sacituzumab govitecan might be an effective treatment for salivary gland cancer?

Research shows that sacituzumab govitecan targets a protein called Trop-2, found in many cancer cells. This treatment has shown promise in other cancers by delivering chemotherapy directly to these cells, helping to shrink tumors. Studies have demonstrated that sacituzumab govitecan can assist patients with various solid tumors, including breast cancer. In trials with these cancers, it slowed disease progression and improved survival rates. This trial will evaluate sacituzumab govitecan in two separate cohorts for salivary gland cancer: one for ACC and another for non-ACC. Although data for salivary gland cancer is limited, its similar mechanism suggests potential benefits for this condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with recurrent/metastatic salivary gland cancer, not suitable for surgery or radiotherapy. Must have good performance status (ECOG 0 or 1), adequate blood counts, liver and kidney function. Men and women must use effective contraception. Excludes those who've had recent cancer treatments, other active cancers (with some exceptions if disease-free for a year), known drug hypersensitivity, brain metastases, recent transfusions or therapies, ongoing serious infections, heart failure, pregnancy/breastfeeding.

Inclusion Criteria

I am 18 or older with confirmed recurrent/metastatic salivary gland cancer.

Patients must meet all of the following inclusion criteria to be eligible for participation in this study:

Patients must have measurable disease per RECIST 1.1

Exclusion Criteria

Current participation in another interventional clinical study

I haven't had radiation or similar treatments in the last 2 weeks.

Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan by vein on Days 1 and 8 of each cycle. The first dose is given over about 3 hours, and subsequent doses over 1-2 hours.

6-12 weeks

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan

Trial Overview

The trial is testing Sacituzumab Govitecan to see if it can control salivary gland cancer better than current treatments. It's given to patients who may have tried other treatments without success or are treatment-naïve in certain cases. The study will monitor the effectiveness by measuring tumor size changes according to RECIST criteria.

How Is the Trial Designed?

Group I: Cohort 2: Non-ACC Experimental Treatment 1 Intervention

Paritcipants will receive sacituzumab govitecan by vein on Days 1 and 8 of each cycle. The first dose will be given over about 3 hours. All other doses will be given over about 1-2 hours. Premedication for prevention of infusion reactions will be administered prior to each sacituzumab govitecan infusion.

Group II: Cohort 1: ACC Experimental Treatment 1 Intervention

Paritcipants will receive sacituzumab govitecan by vein on Days 1 and 8 of each cycle. The first dose will be given over about 3 hours. All other doses will be given over about 1-2 hours. Premedication for prevention of infusion reactions will be administered prior to each sacituzumab govitecan infusion.

Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer
• Locally advanced or metastatic urothelial cancer (withdrawn)
• Metastatic HR+/HER2- breast cancer

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer

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

Nectin-4 is expressed in a significant majority of primary salivary gland carcinomas (80.3%) and their lymph node metastases (90.0%), indicating its potential as a therapeutic target for these cancers.

Patients with salivary duct carcinomas showing higher Nectin-4 expression tended to have better disease-free survival, suggesting that targeting Nectin-4 could improve outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nectin-4 is frequently expressed in primary salivary gland cancer and corresponding lymph node metastases and represents an important treatment-related biomarker. Mayer, M., Nachtsheim, L., Prinz, J., et al.[2023]

Fam-trastuzumab deruxtecan has shown a complete response in a 67-year-old man with HER2-positive metastatic parotid gland carcinoma after previous treatments failed, indicating its potential efficacy in this type of cancer.

This novel antibody-drug conjugate appears to be well-tolerated and effective in patients with HER2-positive salivary gland carcinoma, suggesting it could be a promising treatment option that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic Parotid Gland Carcinoma With ERBB2 Amplification With Complete Response to Fam-Trastuzumab Deruxtecan. Shukla, ND., Chiang, RS., Colevas, AD.[2022]

A total of 1,884 adverse event reports related to sacituzumab govitecan were analyzed, identifying 114 adverse event signals, with most occurring within 30 days of treatment initiation, highlighting the importance of monitoring for early reactions.

Risk factors for hospitalization due to adverse events included being male and experiencing conditions like colitis, febrile neutropenia, and sepsis, indicating specific patient profiles that may require closer observation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). Li, X., Zhang, L., Hu, S., 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]

This case presents the first documented instance of a metastatic salivary duct carcinoma (SDC) that is HER2-positive, which is a rare and challenging condition to diagnose and treat.

The patient was successfully treated using a combination of dual anti-HER2 therapy along with chemotherapy, showcasing a potential effective treatment strategy for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-positive metastatic, parotid salivary duct carcinoma treated with a trastuzumab/pertuzumab-based chemotherapy: A case report. Longo, R., Legros, PO., Talbi, M., et al.[2020]

In a study of six patients with metastatic salivary gland carcinoma treated with trastuzumab and a taxane, the therapy was well tolerated and resulted in five partial responses and a median progression-free survival of 10.8 months, indicating its efficacy.

One patient achieved a complete and durable remission, and trastuzumab showed greater activity than androgen deprivation therapy when both HER-2 and androgen receptors were co-expressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic HER-2-positive salivary gland carcinoma treated with trastuzumab and a taxane: a series of six patients. De Block, K., Vander Poorten, V., Dormaar, T., et al.[2017]

In a study of 13 patients with recurrent or metastatic HER2-positive salivary duct carcinoma, the combination treatment of docetaxel, trastuzumab, and pertuzumab (DTP) resulted in a 58% objective response rate, indicating that this regimen is effective as a first-line therapy.

Following progression, the second-line treatment with ado-trastuzumab emtansine (T-DM1) also showed promising results, with a 57% response rate, and the overall survival after starting DTP was a median of 42 months, suggesting a favorable long-term outcome with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case series of docetaxel, trastuzumab, and pertuzumab (DTP) as first line anti-HER2 therapy and ado-trastuzumab emtansine (T-DM1) as second line for recurrent or metastatic HER2-positive salivary duct carcinoma. Uijen, MJM., Lassche, G., van Engen-van Grunsven, ACH., et al.[2022]

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 (SG) is an FDA-approved antibody-drug conjugate that has shown significant efficacy in treating metastatic triple-negative breast cancer, improving health-related quality of life and prolonging progression-free and overall survival in patients who have undergone multiple prior therapies.

Ongoing clinical trials are exploring the potential of SG for broader applications, including neoadjuvant and adjuvant therapies, combinations with immunotherapy, and treatment of various solid tumors, indicating its promise as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. Veeraballi, S., Khawar, Z., Aslam, HM., et al.[2023]

Citations

1.

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 ...

2.

aetna.com

aetna.com/cpb/medical/data/900_999/0971.html

Sacituzumab Govitecan-hziy (Trodelvy) - Medical Clinical ...

The recommended dose is 10 mg/kg once weekly on Days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity.

3.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2020/761115Orig1s000MultidisciplineR.pdf

761115Orig1s000 - accessdata.fda.gov

No integrated efficacy analysis was performed during this review. Based on the data submitted from IMMU-132-01, sacituzumab govitecan demonstrates evidence.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8633075/

Trophoblast Cell Surface Antigen 2 (Trop-2) Protein is ...

Sacituzumab govitecan (IMMU-132), an Anti-Trop-2/SN-38 antibody-drug conjugate: characterization and efficacy in pancreatic, gastric, and other cancers.

5.

askgileadmedical.com

askgileadmedical.com/docs/trodelvy/trodelvy-use-in-patients-with-head-and-neck-cancer

Trodelvy® (sacituzumab govitecan-hziy) Use in Patients ...

TROPiCS-03 is a phase 2 study evaluating the efficacy and safety of SG in adult patients with metastatic solid tumors, including patients with R/R advanced ...

6.

ichgcp.net

ichgcp.net/clinical-trials-registry/NCT06923826

Sacituzumab govitecan in Thyroid Cancer and Salivary Gland ...

The goal of this clinical trial is to learn if the drug, sacituzumab govitecan, works to treat:Salivary gland cancers that have spread to other parts of the ...