Sacituzumab Govitecan for Ovarian Cancer

Overseen By Lisa Baker, R.N.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: UGT1A1 inhibitors

Disqualifiers: Pregnancy, Cardiac disease, 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: 21

Duration: Until progression or adverse effects

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called sacituzumab govitecan, an antibody-drug conjugate, for women with certain types of ovarian cancer that have not responded to standard platinum-based chemotherapy. The goal is to determine if this treatment can control the cancer or reduce its size. Women with ovarian, fallopian tube, or primary peritoneal cancer that has recurred or persisted after treatment and does not respond to platinum drugs may be suitable candidates. Participants must have a tumor that doctors can measure to track changes during the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be at least 2 weeks beyond prior treatments like chemotherapy or radiation, and a 4-week washout period is required if you had prior immunotherapy. Some medications, like UGT1A1 inhibitors, are prohibited.

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

Research shows that sacituzumab govitecan is generally safe and well-tolerated. Studies, particularly those involving cancer patients, have found no unexpected safety issues. For example, a study with patients who had heavily treated, platinum-resistant ovarian cancer found sacituzumab govitecan to be a promising treatment with manageable side effects.

Additionally, early results from another study indicate that the treatment was well-tolerated, with no new or surprising safety concerns. The side effects were similar to those seen in previous research, allowing doctors to predict and manage them effectively.

Overall, existing research suggests that sacituzumab govitecan is reasonably safe for treating certain cancers. ^{1 2 3 4 5}

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

Unlike the standard treatments for ovarian cancer, which often include chemotherapy and targeted therapies, sacituzumab govitecan is unique because it is an antibody-drug conjugate. This means it combines an antibody specifically designed to target cancer cells with a potent chemotherapy drug. This targeted approach allows the treatment to deliver the chemotherapy directly to the cancer cells, potentially minimizing harm to healthy cells and reducing side effects. Researchers are excited about sacituzumab govitecan because it has the potential to be more effective and have fewer side effects than traditional chemotherapy, offering new hope for patients with ovarian cancer.

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

Research suggests that sacituzumab govitecan, which participants in this trial will receive, could treat ovarian cancer that doesn't respond to platinum-based chemotherapy. Some studies indicate it might be an option for patients who haven't had success with other chemotherapy treatments. However, the results are mixed. In one study, no patients experienced tumor shrinkage, but two patients maintained stable disease, meaning their cancer did not worsen. While the results aren't very strong, they suggest that sacituzumab govitecan might help some patients manage their cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Alessandro Santin

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with platinum-resistant ovarian cancer, including fallopian tube or primary peritoneal cancers, who have had no more than two prior chemotherapies for recurrent disease. Participants must be in good health otherwise, not pregnant or breastfeeding, and able to use contraception. They should have recovered from previous treatments and surgeries and have adequate organ function.

Inclusion Criteria

My surgery removed most or all of my tumor.

Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the study entry and must agree to use protocol-specific method(s) of contraception.

My cancer has come back and can be measured.

Exclusion Criteria

You have Gilbert's disease.

I have an uncontrolled seizure disorder or an active neurological disease.

I am not currently taking, nor have I previously taken, any medications that are not allowed in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan, 10 mg/kg for the first 2 weeks of a 21-day cycle until progression or adverse effects prohibit further treatment

Until progression or adverse effects

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab govitecan

Trial Overview The study tests Sacituzumab Govitecan (IMMU-132) on patients with specific types of ovarian cancer that are resistant to platinum-based chemotherapy. It's a Phase 2 trial focusing on those whose disease has returned after treatment. The drug's effectiveness will be measured against the size of tumors over time.

How Is the Trial Designed?

Group I: Sacituzumab govitecan, 10 mg/kg Experimental Treatment 1 Intervention

Sacituzumab govitecan, 10 mg/kg for the first 2 weeks of 21-day cycle until progression or adverse effects prohibit further treatment

Sacituzumab govitecan is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease
• Locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor
• Unresectable locally advanced or metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting

Approved in European Union as Trodelvy for:

• Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease

Approved in Canada as Trodelvy for:

• Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Alessandro Santin

Lead Sponsor

Trials

4

Recruited

140+

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

Published Research Related to This Trial

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]

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]

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]

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, 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]

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]

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 (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]

Citations

1. onclive.com onclive.com/view/sacituzumab-govitecan-upholds-efficacy-and-safety-in-real-world-mtnbc-population

Sacituzumab Govitecan Upholds Efficacy and Safety in ... Sacituzumab govitecan demonstrated consistent efficacy and safety in real-world mTNBC patients, with median OS of 11.3 months and PFS of 5.0 ...

2. 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- ...

3. 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.

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 summarize the final safety results from the full safety population in the IMMU-132-01 study, along with additional efficacy data from ...

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 ...

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

Preliminary results of a phase II trial with sacituzumab ... The treatment was well-tolerated with no new or unexpected safety signals reported. Conclusions: Sacituzumab govitecan shows remarkable clinical ...