Sacituzumab Govitecan for Salivary Gland Cancer

Overseen by Renata Ferrarotto

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, others

Disqualifiers: Active CNS disease, uncontrolled infections, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

To learn if sacituzumab govitecan can help to control salivary gland cancer.

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 Sacituzumab Govitecan generally safe for humans?

Sacituzumab Govitecan has been used for treating breast cancer and urothelial carcinoma, with some reported side effects. Common side effects include neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). Most side effects occur within 30 days of starting treatment, and close monitoring is recommended. ^{1 2 3 4 5}

What makes the drug Sacituzumab Govitecan unique for treating salivary gland cancer?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that targets Trop-2, a protein often overexpressed in various cancers, delivering a potent chemotherapy directly to cancer cells. This targeted approach may offer a new option for salivary gland cancer, which lacks many effective treatments. ^{6 7 8 9 10}

Research Team

Renata Ferrarotto

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

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

Patients must have measurable disease per RECIST 1.1

Exclusion Criteria

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

Current participation in another interventional clinical study

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

Trial Timeline

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

Treatment Details

Interventions

• Sacituzumab Govitecan (Monoclonal Antibodies)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

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

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. 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]

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

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). [2023]

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

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. [2023]

6. Netherlands 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. [2023]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Metastatic HER-2-positive salivary gland carcinoma treated with trastuzumab and a taxane: a series of six patients. [2017]

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

Metastatic Parotid Gland Carcinoma With ERBB2 Amplification With Complete Response to Fam-Trastuzumab Deruxtecan. [2022]

10. England pubmed.ncbi.nlm.nih.gov

HER2-positive metastatic, parotid salivary duct carcinoma treated with a trastuzumab/pertuzumab-based chemotherapy: A case report. [2020]