Sacituzumab Govitecan for Endometrial Cancer

Overseen By Alessandro Santin

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Alessandro Santin

Must not be taking: Antiretrovirals, Antiarrhythmics

Disqualifiers: Active second malignancy, Cardiac disease, COPD, CNS metastases, 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: Unknown

Duration: Until disease progression or unacceptable toxicity

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a non-randomized Phase 2 study of sacituzumab govitecan (IMMU-132) in subjects with persistent or recurrent endometrial carcinoma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you need to be at least 2 weeks beyond any prior treatments like chemotherapy, investigational drugs, or high-dose corticosteroids before starting the trial.

What data supports the effectiveness of the drug Sacituzumab Govitecan for endometrial cancer?

Sacituzumab Govitecan has shown promising results in laboratory studies for uterine serous carcinoma, a type of endometrial cancer, by targeting a specific protein on cancer cells to deliver a cancer-fighting substance. Additionally, it has been effective in treating other cancers like triple-negative breast cancer, which suggests potential benefits for endometrial cancer as well. ^{1 2 3 4 5}

What safety data exists for Sacituzumab Govitecan in humans?

Sacituzumab Govitecan has shown acceptable safety in clinical trials for various cancers, including breast cancer, with a well-defined and manageable toxicity profile. Rapid recognition and proactive management of side effects are important to optimize treatment and maintain quality of life. ^{3 4 6 7 8}

What makes the drug Sacituzumab Govitecan unique for treating endometrial cancer?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that specifically targets the Trop-2 protein, which is often overexpressed in aggressive forms of endometrial cancer, to deliver a potent chemotherapy agent directly to cancer cells, potentially improving treatment effectiveness. ^{3 4 5 6 9}

Research Team

Alessandro Santin

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults with persistent or recurrent endometrial carcinoma that worsened after platinum-based chemotherapy. They must have measurable disease, adequate organ function, and an ECOG performance status of 0 or 1. Participants need to be at least two weeks past prior treatments and recovered from acute toxicities. Pregnant women are excluded, as well as those with active second cancers, significant heart conditions, unstable medical issues, CNS metastases, certain viral infections, bleeding disorders or a history of severe reactions to similar drugs.

Inclusion Criteria

My liver functions are within the required range.

Patients must have signed an approved informed consent.

I can provide a sample of my tumor for TROP-2 testing.

Exclusion Criteria

I have stable brain metastases, not on high steroids, and no carcinomatous meningitis.

I have HIV with a high viral load and take medication that could affect my treatment.

I do not have an active second cancer, or it has been in remission for over 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Sacituzumab govitecan is administered at 10 mg/kg weekly as an infusion for 2 consecutive weeks followed by 1 week without treatment, representing a 3-week cycle. Treatment continues in the absence of disease progression or unacceptable toxicity.

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including adverse events and survival outcomes.

6 years

Treatment Details

Interventions

• Sacituzumab Govitecan

Trial Overview The study tests Sacituzumab Govitecan (IMMU-132) in patients with endometrial cancer that has returned or persisted despite previous treatment. It's a Phase 2 trial where all participants receive the drug without being randomly assigned to different groups.

Participant Groups

Group I: Sacituzumab Govitecan Experimental Treatment 1 Intervention

Sacituzumab govitecan will be administered at 10 mg/kg weekly as an infusion for 2 consecutive weeks (2 weekly doses plus 1 week without treatment represents a single 3 week cycle). Treatment can be continued without a rest period in the absence of progression of disease or unacceptable toxicity.

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?

Alessandro Santin

Lead Sponsor

Trials

4

Recruited

140+

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

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

Findings from Research

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 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]

Trop-2 was found to be expressed in 95.1% of uterine serous carcinoma (USC) samples, indicating that targeting this protein with sacituzumab govitecan (SG) could be a promising treatment strategy for most USC patients.

In preclinical studies, SG demonstrated significant anti-tumor activity against Trop-2 positive USC cell lines and xenografts, leading to growth inhibition and increased survival in treated mice, suggesting its potential efficacy in advanced or recurrent USC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Han, C., Perrone, E., Zeybek, B., et al.[2020]

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]

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]

Sacituzumab govitecan (TRODELVY) is an effective treatment for metastatic triple-negative breast cancer, showing promising results in a phase I/II study and receiving accelerated FDA approval for patients who have undergone at least two prior therapies.

The drug has a well-defined and manageable toxicity profile, and proactive management of adverse events is crucial for optimizing treatment duration and maintaining patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. Spring, LM., Nakajima, E., Hutchinson, J., et al.[2021]

Sacituzumab govitecan (SG) showed promising efficacy in treating advanced epithelial cancers, with partial response rates of 22.2% in endometrial cancer and 17.7% in small-cell lung cancer, indicating its potential as a treatment option.

The safety profile of SG was consistent with previous studies, with common treatment-related adverse events including neutropenia (57.8%) and nausea (62.6%), and a notable incidence of grade ≥3 neutropenia in patients with specific genetic variations (UGT1A1∗28 homozygotes).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Bardia, A., Messersmith, WA., Kio, EA., et al.[2021]

A study analyzing 1072 cases from the FDA Adverse Event Reporting System identified significant safety concerns with Sacituzumab Govitecan, particularly related to blood and lymphatic system disorders, gastrointestinal issues, and severe infections like neutropenic sepsis and colitis.

Unexpected serious safety signals were also noted, including large intestine perforation and hepatic failure, with geriatric patients being at a notably higher risk for several adverse events, highlighting the need for careful monitoring and management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing real-world safety concerns of Sacituzumab govitecan: a disproportionality analysis using spontaneous reports in the FDA adverse event reporting system. Gui, X., Zhao, J., Ding, L., et al.[2023]

In a phase II study involving 113 patients with metastatic urothelial carcinoma who had previously progressed on platinum-based chemotherapy and checkpoint inhibitors, sacituzumab govitecan (SG) demonstrated an objective response rate of 27%, indicating significant efficacy in this difficult-to-treat population.

SG was associated with a manageable safety profile, with the most common severe side effects being neutropenia (35%) and diarrhea (10%), leading to a 6% discontinuation rate due to treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. Tagawa, ST., Balar, AV., Petrylak, DP., et al.[2022]

References

1. United States 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. [2018]

2. 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]

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

In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. [2020]

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

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Assessing real-world safety concerns of Sacituzumab govitecan: a disproportionality analysis using spontaneous reports in the FDA adverse event reporting system. [2023]

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

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. [2022]