Sacituzumab Govitecan for Ovarian Cancer

Overseen By Valentina Bolanos, R.N.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: UGT1A1 inhibitors, Topoisomerase 1 inhibitors

Disqualifiers: Other malignancies, Brain 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

Compensation: Varies

Number of Visits: 10

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether the drug sacituzumab govitecan (SG) can treat ovarian, endometrial, or cervical cancers that have returned after at least two standard treatments. Researchers have already used SG in other cancers and now want to determine its effectiveness for these types. The trial involves receiving SG infusions in 21-day cycles. Individuals whose cancer has returned after two rounds of treatment and who have measurable disease might be suitable candidates. Participants will undergo various tests, including imaging scans and biopsies, to monitor progress throughout the study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of 3 weeks for prior cancer-directed therapy and 4 weeks for prior cancer-directed immunotherapy before starting the study treatment. If you are on other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that sacituzumab govitecan (SG) is generally well-tolerated by patients with various types of cancer. In a study with 495 participants, only 8.3% stopped treatment due to side effects. This indicates that while side effects can occur, they typically do not lead most patients to discontinue treatment.

Another study focused on ovarian cancer patients who had previously tried several treatments. It found that sacituzumab govitecan might be a viable option for those whose cancer did not respond to standard chemotherapy.

This drug is already approved for other types of cancer, which can reassure patients about its safety. However, like any treatment, potential risks and side effects can vary from person to person. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sacituzumab govitecan is unique because it combines a targeted antibody with chemotherapy, specifically designed to attack cancer cells more precisely. While most treatments for ovarian cancer, like platinum-based chemotherapy, work by attacking rapidly dividing cells indiscriminately, sacituzumab govitecan targets the Trop-2 protein, which is often overexpressed in ovarian cancer cells. This targeted approach not only aims to enhance the destruction of cancer cells but also potentially reduces damage to healthy cells, making it an exciting development in the fight against ovarian cancer.

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

Studies have shown that sacituzumab govitecan (SG), the treatment tested in this trial, could be a promising option for some difficult-to-treat cancers. Research indicates it has effectively targeted several solid tumors, including ovarian and endometrial cancers. Specifically, in patients with ovarian cancer, SG stabilized the disease in about 25% of cases, offering a potential option for those unresponsive to other treatments. SG targets a protein called Trop-2, found on many cancer cells, to deliver chemotherapy directly to the cancer. While results can vary, these findings suggest SG might offer new hope for patients with recurring ovarian cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Kevin C Conlon, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with ovarian, endometrial, or cervical cancer that has returned after at least two standard treatments. Participants must have completed prior therapies and be able to provide tissue samples from their tumors.

Inclusion Criteria

I have recurrent ovarian cancer that is resistant to platinum-based treatments.

I have endometrial cancer that hasn't responded to standard treatments and have tried or can't try anti-PD-1/PD-L1 therapy.

I have cervical cancer that has come back and doesn't respond to standard treatments.

Exclusion Criteria

Participants who are receiving any other investigational agents

My ovarian cancer did not respond to initial platinum-based chemotherapy.

I have a history of serious GI or lung-related issues.

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 (SG) intravenously on Days 1 and 8 of each 21-day cycle

Up to 5 years

Days 1 and 8 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 6 months (phone contact)

End-of-Treatment

Participants have an end-of-treatment visit within 2 weeks and a safety visit about 30 days after they stop treatment

6 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan

Trial Overview The trial is testing Sacituzumab Govitecan (SG), a drug approved for other cancers, on those with relapsed ovarian, endometrial, or cervical cancers. Patients will receive SG infusions in cycles of 21 days for up to five years if beneficial.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

Treatment with sacituzumab govitecan (SG)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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, 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]

Sacituzumab govitecan (SG) showed a clinically significant advantage over chemotherapy for treating HR+/HER2- metastatic breast cancer, providing an increase of 0.284 life years and 0.217 quality-adjusted life years (QALYs).

However, SG was not considered cost-effective at the current pricing, with an incremental cost-effectiveness ratio (ICER) of $612,772/QALY, indicating that substantial price reductions would be necessary for it to be deemed cost-effective from a third-party payer perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Shi, D., Li, Y., Liang, X., et al.[2023]

A study analyzing 2069 reports of sacituzumab govitecan (SG) from the FDA Adverse Event Reporting System found that SG is significantly associated with increased risks of blood lymphatic system disorders and hepatobiliary disorders, indicating important safety concerns for patients.

In addition to common adverse events like anemia and neutropenia, the study identified unexpected significant adverse events such as colitis and meningitis, highlighting the need for ongoing monitoring and safety management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety surveillance of sacituzumab govitecan: an observational, pharmacovigilance study leveraging FAERS database. Liu, W., Du, Q., Guo, Z., et al.[2023]

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 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]

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]

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 (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]

Sacituzumab-govitecan (SG) demonstrated significant antitumor activity in carcinosarcoma (CS) models, particularly in tumors expressing the Trop-2 marker, with a notable improvement in overall survival at 90 days compared to control groups.

In vitro studies showed that Trop-2 positive cell lines were more sensitive to SG, indicating that Trop-2 expression could be a key factor in determining the efficacy of this treatment for patients with carcinosarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Lopez, S., Perrone, E., Bellone, S., et al.[2022]

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/NCT06028932

NCT06028932 | A Study of Sacituzumab Govitecan (IMMU- ... This is an open-label, Phase 2 study designed to assess the clinical activity of sacituzumab govitecan in subjects with recurrent or persistent platinum- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11300917/

Sacituzumab govitecan in heavily pretreated, platinum- ... Sacituzumab govitecan may represent a treatment option for platinum-resistant/recurrent HGSOC that have previously failed prior lines of chemotherapy.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS5623

A single-center, open-label, single-arm, phase I study with ... Sacituzumab govitecan has demonstrated in vitro and in vivo activity against multiple solid tumors, including ovarian cancer and endometrial ...

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

(sacituzumab govitecan-hziy) - Use in Ovarian Cancer The ORR in patients with EOC was 0%. Stable disease was achieved by 2 patients (25% of patients with EOC). The median DOR, median OS, median PFS, and CBR were ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2821%2900883-8/fulltext

Sacituzumab govitecan, a Trop-2-directed antibody-drug ... Here, we presented study results on the efficacy of SG in different cohorts (CRC, esophageal, endometrial, CRPC, pancreatic, and SCLC) that have ...