Sacituzumab Govitecan for Ovarian Cancer

Overseen By Jung-Min Lee, M.D.

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

95 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Cancers of the female reproductive organs often come back after treatment. A drug called sacituzumab govitecan (SG) has been approved for use in other types of cancers. Researchers want to see if SG can also help people with ovarian, endometrial, or cervical cancers. Objective: To test SG in people with ovarian, endometrial, or cervical cancers. Eligibility: People aged 18 years and older with ovarian, endometrial, or cervical cancer. Their cancers must have returned after at least 2 rounds of standard treatments. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and a test of their heart function. They also will have biopsies to get new tissues samples taken from their tumors. SG is infused through a tube attached to a needle inserted into a vein in the arm. Treatment will be given in 21-day cycles. Participants will receive SG on days 1 and 8 of each cycle. Each infusion takes 1 to 3 hours. Participants may receive SG for up to 5 years. They can continue as long as the drug is helping them. Imaging scans and other tests will be repeated throughout the study period. Participants will have an end-of-treatment visit within 2 weeks and a safety visit about 30 days after they stop treatment. Physical exams, blood tests, and imaging scans may be repeated. Participants will then be contacted by phone every 6 months for up to 10 years after their first dose of SG. Sponsoring Institution: National Cancer Institute

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.

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

Sacituzumab Govitecan has shown antitumor activity in various cancers, including aggressive uterine and ovarian carcinosarcomas, and has demonstrated effectiveness in other epithelial cancers and metastatic triple-negative breast cancer, suggesting potential benefits for ovarian cancer. ^{1 2 3 4 5}

What safety information is available for Sacituzumab Govitecan?

Sacituzumab Govitecan has been associated with some safety concerns, including blood disorders like anemia (low red blood cell count) and neutropenia (low white blood cell count), as well as diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). Most side effects occur within the first month of treatment, and it's important for doctors to monitor these reactions closely. ^{3 6 7 8 9}

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

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate (ADC) that specifically targets a protein called Trop-2 on cancer cells, delivering a potent chemotherapy agent (SN-38) directly to the tumor, which may enhance its effectiveness and reduce side effects compared to traditional chemotherapy. ^{1 3 4 10 11}

Research Team

Jung-Min Lee, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 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 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]

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]

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]

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]

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]

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 (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]

References

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

Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. [2022]

2. United States 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. [2022]

3. 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]

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. 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]

6. 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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Post-marketing safety surveillance of sacituzumab govitecan: an observational, pharmacovigilance study leveraging FAERS database. [2023]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. [2023]

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

Sacituzumab Govitecan: First Approval. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. [2023]