Sacituzumab Govitecan for Glioblastoma

Recruiting at 5 trial locations

Overseen By Kelly Juniper

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Bevacizumab, Warfarin, Enzyme-inducing antiepileptics

Disqualifiers: Hypertension, Cardiac arrhythmias, Infection, 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: 2

Duration: 6 months

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called Sacituzumab Govitecan, an antibody-drug conjugate, for individuals with recurring brain tumors known as glioblastoma. The goal is to determine if this treatment extends survival compared to the older treatment, lomustine. It includes participants whose tumors exhibit high levels of a specific protein called Trop-2. Those who have previously undergone radiation and chemotherapy and experienced tumor progression may be suitable candidates. Participants must be willing to forgo certain other treatments during the study. As a Phase 2 trial, this 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 does not specify if you must stop all current medications, but you cannot take certain medications like enzyme-inducing anti-epileptic drugs within 14 days of the study drug. If you're on warfarin, you need to switch to low molecular weight heparin before starting the trial.

Is there any evidence suggesting that Sacituzumab Govitecan is likely to be safe for humans?

Previous studies have generally found Sacituzumab Govitecan to be well-tolerated by patients with epithelial cancers, including some brain tumors. Research shows that common side effects include nausea, tiredness, and low blood cell counts. However, these side effects are often manageable and do not affect everyone.

In patients with recurrent glioblastoma (a type of brain tumor), early studies have shown promising safety results. Dr. William Kelly noted that the treatment's safety aligns with observations in other cancers, indicating no unexpected or severe safety issues specific to glioblastoma patients.

Sacituzumab Govitecan combines an antibody with a drug to target cancer cells more precisely. This targeted approach usually reduces side effects compared to more traditional therapies.

Overall, while any treatment can have risks, the safety data for Sacituzumab Govitecan is promising, especially given its success in other cancers. ^{1 2 3 4 5}

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

Sacituzumab govitecan is unique because it combines a targeted therapy with a potent chemotherapy agent, specifically aiming at a protein called Trop-2, which is overexpressed in many cancers, including glioblastoma. Unlike traditional treatments for glioblastoma, which primarily rely on surgery, radiation, and the chemotherapy drug temozolomide, sacituzumab govitecan delivers its chemotherapy payload directly to cancer cells, potentially enhancing effectiveness while minimizing damage to healthy cells. Researchers are excited about this approach as it promises a more precise attack on cancer cells, which could lead to improved outcomes for patients with this aggressive brain tumor type.

What evidence suggests that Sacituzumab Govitecan might be an effective treatment for Glioblastoma?

Research has shown that Sacituzumab Govitecan (SG), the treatment under study in this trial, may effectively treat cancers with high levels of the protein TROP-2, often found in tumor cells. In early studies with patients who have recurrent glioblastoma (a type of brain tumor), SG demonstrated positive results in terms of safety and effectiveness. This treatment has already proven effective in other cancers, such as breast cancer that has spread to the brain. These findings suggest that SG targets and attacks cancer cells, potentially improving survival rates for glioblastoma patients. While more research is needed, the initial results are promising for those with tumors exhibiting high levels of TROP-2. ^{1 3 4 5 6}

Who Is on the Research Team?

William Kelly, MD

Principal Investigator

Mays Cancer Center, UT Health San Antonio

Are You a Good Fit for This Trial?

Adults with confirmed IDH wild-type glioblastoma that has progressed after standard treatment, including radiation and chemotherapy. Participants must have stable vital signs, acceptable blood counts, liver and kidney function, agree to use contraception, and not be pregnant or breastfeeding. They should not have had certain recent treatments or surgeries and must be willing to stop using tumor treatment field therapy.

Inclusion Criteria

I have recovered from previous treatment side effects, except for mild neuropathy or hair loss.

My biological samples are available for further testing.

I understand the study's risks and have signed the consent form.

Exclusion Criteria

I have a serious health condition like uncontrolled high blood pressure or heart issues.

I am taking warfarin or similar drugs and cannot switch to LMWH before starting the study drug.

The subject is unable to undergo MRI scan (eg, has pacemaker).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Sacituzumab Govitecan at 10 mg/kg on days 1 and 8 of a 21-day cycle

6 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan

Trial Overview The trial is testing Sacituzumab Govitecan as a single agent in an open-label setting for recurrent glioblastoma patients. Everyone in the study will receive this investigational drug to evaluate its effectiveness against this type of brain cancer.

How Is the Trial Designed?

Group I: Sacituzumab govitecan Experimental Treatment 1 Intervention

Dosing will be at 10 mg/kg on days 1 and 8 of a 21-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?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Published Research Related to This Trial

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 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) 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, shows promise in treating malignant pleural mesothelioma (MPM), particularly in TROP-2-positive cell lines, as it effectively induces cell cycle arrest and cell death.

TROP-2 was expressed in 6 out of 17 MPM cell lines, and sensitivity to the drug SN38 was observed in 10 of these lines, suggesting that TROP-2 expression could serve as a biomarker for selecting patients who may benefit from sacituzumab govitecan therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROP2 expression and SN38 antitumor activity in malignant pleural mesothelioma cells provide a rationale for antibody-drug conjugate therapy. Hegedüs, L., Okumus, Ö., Mairinger, F., 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 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 (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) 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/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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11306739/

Sacituzumab Govitecan in patients with breast cancer brain ... Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers.

3. askgileadmedical.com askgileadmedical.com/docs/trodelvy/trodelvy-use-in-patients-with-recurrent-glioblastoma

Trodelvy® Use in Patients with Recurrent GBM Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of- opportunity trial. Nat Commun. 2024;15( ...

4. onclive.com onclive.com/view/dr-kelly-on-early-efficacy-signals-and-safety-with-sacituzumab-govitecan-in-recurrent-glioblastoma

Dr Kelly on Early Efficacy Signals and Safety With ... William Kelly, MD, discusses the safety and efficacy signals seen with sacituzumab govitecan in a phase 2 study of patients with recurrent glioblastoma.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/761115Orig1s000MultidisciplineR.pdf

761115Orig1s000 - accessdata.fda.gov evidence of effectiveness. The effectiveness of sacituzumab govitecan (IMMU-132) was demonstrated in study IMMU-132-01, single-arm trial. An overall response ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0923753421008838

Sacituzumab govitecan, a Trop-2-directed antibody-drug ... This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously ...