Sacituzumab Govitecan for Endometrial Cancer

(ASCENT-GYN-01 Trial)

Recruiting at 214 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must not be taking: Trop-2 ADCs

Disqualifiers: Uterine leiomyosarcoma, Active second malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 1

Duration: 21-28 days per cycle, up to approximately 47 months

640 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called sacituzumab govitecan to determine if it helps people with endometrial cancer live longer without disease progression. It compares sacituzumab govitecan with other treatments, such as doxorubicin or paclitaxel, chosen by the doctor. The trial seeks participants with endometrial cancer that has recurred or persisted after platinum-based chemotherapy and immunotherapy. Those previously treated with these therapies and ineligible for curative treatment may qualify for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial 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 well-tolerated by patients. Studies have found that SG is safe for individuals who have undergone previous treatments, even those with difficult-to-treat cancers. While some side effects occurred, they were typically expected with cancer treatments.

In some trials, patients experienced side effects, but these were often mild to moderate. The most common side effects included nausea, tiredness, and low blood cell counts, which are typical for many cancer treatments.

Overall, the safety profile of SG suggests it is reasonably safe, especially for those who have already received other treatments. However, potential participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

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

Sacituzumab Govitecan is unique because it targets a specific protein called Trop-2, which is often overexpressed in endometrial cancer cells. Unlike standard treatments such as Doxorubicin and Paclitaxel, which are traditional chemotherapy drugs, Sacituzumab Govitecan is an antibody-drug conjugate, combining a targeted antibody with a potent chemotherapy agent. Researchers are excited because this targeted approach aims to deliver the chemotherapy directly to the cancer cells, potentially increasing effectiveness while minimizing damage to healthy cells.

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

In this trial, participants will receive either sacituzumab govitecan (SG) or a treatment of physician's choice (TPC). Studies have shown that SG could effectively treat endometrial cancer, especially in patients who haven't responded well to treatments like platinum-based chemotherapy and immunotherapy. Research indicates that SG works well against difficult-to-treat, chemotherapy-resistant forms of endometrial cancer. Specifically, earlier trials showed promising results for SG in terms of effectiveness and safety, offering hope for those with advanced or spreading endometrial cancer. Overall, these findings suggest SG could improve outcomes for patients with limited treatment options. ^{1 3 4 5 6}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent or persistent endometrial cancer who have already undergone platinum-based chemotherapy and immunotherapy. They should be fit enough for treatment, as indicated by a performance status score of 0 or 1, and must have disease that can be measured by scans. Participants should not have had more than three prior systemic treatments.

Inclusion Criteria

I am eligible for treatment with doxorubicin or paclitaxel.

My organs are working well.

I have had up to 3 treatments for endometrial cancer, including platinum-based and anti-PD-1/PD-L1 therapies.

Exclusion Criteria

I have been diagnosed with a specific type of uterine cancer.

I am currently being treated for a serious infection with medication.

My doctor thinks I can try platinum-based chemotherapy again.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sacituzumab govitecan or treatment of physician's choice

21-28 days per cycle, up to approximately 47 months

Visits on Days 1 and 8 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 47 months

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan

Trial Overview The study compares the effectiveness of sacituzumab govitecan (SG), a new drug, against the physician's choice of standard treatments like doxorubicin or paclitaxel in extending the time patients live without their disease getting worse (PFS) and overall survival (OS).

How Is the Trial Designed?

Group I: Sacituzumab Govitecan (SG) Experimental Treatment 1 Intervention

Participants will receive SG at a dose of 10 mg/kg on Days 1 and 8 of a 21-day cycle.

Group II: Treatment of Physician's Choice (TPC) Active Control 2 Interventions

Participants will receive one of the following TPC, regimens determined prior to randomization. * Doxorubicin 60 mg/m\^2 IV on Day 1 of a 21-day cycle * Paclitaxel 80 mg/m\^2 IV on Days 1, 8, and 15 of a 28-day cycle

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?

Gilead Sciences

Lead 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

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Asia-Pacific Gynecologic Oncology Trials Group (APGOT)

Collaborator

Trials

3

Recruited

1,200+

Published Research Related to This Trial

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) is an effective treatment for locally advanced and metastatic urothelial cancer, showing a 27% objective response rate in the TROPHY-U-01 phase II trial.

While SG has common side effects like diarrhea and neutropenia, these can be managed with supportive care, and it has received accelerated approval for patients who have previously undergone platinum-based chemotherapy and PD-1 or PD-L1 inhibitor treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. Mathew Thomas, V., Tripathi, N., Agarwal, N., et al.[2022]

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 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]

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]

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 (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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11458108/

Efficacy and Safety of Sacituzumab Govitecan in Patients With ... Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have poor prognosis.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04251416

NCT04251416 | A Study of Sacituzumab Govitecan (IMMU- ... This is a non-randomized Phase 2 study of sacituzumab govitecan (IMMU-132) in subjects with persistent or recurrent endometrial carcinoma. Detailed Description.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5599

Preliminary results of a phase II trial with sacituzumab ... Sacituzumab govitecan shows remarkable clinical activity against some of the most historically challenging and chemotherapy-resistant endometrial pathologies.

4. askgileadmedical.com askgileadmedical.com/docs/trodelvy/trodelvy-use-in-endometrial-cancer

Trodelvy® Use in Patients With Endometrial Cancer Efficacy and safety of sacituzumab govitecan in patients with advanced/metastatic endometrial cancer: updated results from TROPiCS-03 (Poster #733P). Presented ...

5. international-journal-of-gynecological-cancer.com international-journal-of-gynecological-cancer.com/article/S1048-891X(25)01774-8/fulltext

A randomized, phase III study of sacituzumab govitecan ... In the phase II TROPiCS-03 trial, sacituzumab govitecan demonstrated encouraging efficacy and manageable safety in heavily pretreated patients ...

6. 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 ...