Sacituzumab Govitecan + Nivolumab for Bladder Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Nataliya Mar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of California, Irvine

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Active malignancy, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a phase 2 study, single-arm study of adjuvant combination therapy with Sacituzumab Govitecan and Nivolumab in patients with muscle-invasive urothelial carcinoma of the bladder, ureter, or upper tract, who are high risk for cancer recurrence post curative-intent surgery based on surgical pathology.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on high-dose corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment.

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

Sacituzumab govitecan has shown preliminary activity in patients with metastatic urothelial carcinoma (a type of bladder cancer) who have limited treatment options after other therapies. It is an antibody-drug conjugate that targets a protein called Trop-2, which is often found in high amounts in these cancers. ^{1 2 3 4 5}

What safety information is available for Sacituzumab Govitecan in humans?

Sacituzumab Govitecan has been associated with side effects like neutropenia (low white blood cell count), diarrhea, colitis (inflammation of the colon), and sepsis (a severe infection). These side effects often occur within 30 days of starting treatment, and some can lead to hospitalization, especially in males. ^{2 3 4 6 7}

How is the drug Sacituzumab Govitecan + Nivolumab unique for bladder cancer?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate that targets Trop-2, a protein found in many cancers, and delivers a chemotherapy agent directly to cancer cells. This approach is different from traditional chemotherapy as it aims to reduce side effects by specifically targeting cancer cells. Nivolumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells, making this combination a novel approach for treating bladder cancer. ^{1 2 3 6 8}

Eligibility Criteria

This trial is for individuals with muscle-invasive urothelial carcinoma, which includes cancers of the bladder, ureter, or upper tract. It's specifically for those at high risk of cancer coming back after surgery meant to cure them.

Inclusion Criteria

I am 18 years old or older.

My cancer started in the bladder, ureter, or renal pelvis and is not small cell carcinoma.

Radiographic disease-free status as determined by imaging within 28 days of C1 D1 of study treatment

Exclusion Criteria

I haven't had any cancer except for certain types in the last 3 years.

I have or might have an autoimmune disease.

I have had radiation therapy for urinary cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with Sacituzumab Govitecan and Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles

15 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Nivolumab (Monoclonal Antibodies)
• Sacituzumab Govitecan (Monoclonlonal Antibodies)

Trial Overview The study is testing a combination therapy using two drugs: Sacituzumab Govitecan and Nivolumab. As it's a phase 2 single-arm study, all participants will receive this combo treatment to see how effective it is in preventing cancer recurrence.

Participant Groups

Group I: Sacituzumab Govitecan PLUS Nivolumab Experimental Treatment 2 Interventions

Patients eligible for this study treatment will receive combination therapy with Sacituzumab Govitecan with Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Chao Family Comprehensive Cancer Center, University of California, Irvine Orange, CA

Who Is Running the Clinical Trial?

University of California, Irvine Lead Sponsor

Gilead Sciences Industry Sponsor

References

1. 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] Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2-directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

2. England pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. [2022] Despite rapid advances in the treatment landscape of urothelial cancer, there is a substantial unmet need for safe and effective therapies for patients with locally advanced and metastatic urothelial cancer. Sacituzumab govitecan (SG) is an antibody-drug conjugate, consisting of a Trop-2 directed monoclonal antibody linked to SN-38, the active metabolite of irinotecan. Trop-2 is a glycoprotein overexpressed in various carcinomas, including urothelial carcinomas.

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

Sacituzumab Govitecan: First Approval. [2021] Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.

4. England pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. [2023] The antibody-drug conjugates sacituzumab govitecan (SG) and enfortumab vedotin (EV) are standard monotherapies for metastatic urothelial carcinoma (mUC). Given the different targets and payloads, we evaluated the safety and efficacy of SG + EV in a phase I trial in mUC (NCT04724018).

5. England pubmed.ncbi.nlm.nih.gov

The role of enfortumab vedotin and sacituzumab govitecan in treatment of advanced bladder cancer. [2022] The treatment landscape of advanced bladder cancer continues to evolve with novel therapeutics approved in recent years and many in the pipeline. Here we review the role of the novel agents enfortumab vedotin and sacituzumab govitecan in treatment of advanced disease.

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021] To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease.

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

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). [2023] Sacituzumab govitecan(SG)is wide used for the treatment of breast cancer and urothelial carcinoma, but available information regarding AEs is limited. We aim to explore the AE induced by SG by mining the FAERS database.The association between SG and adverse events (AEs) were evaluated using the information component (IC). A multivariate logistic regression analysis was conducted for all identified signals to explore the risk factors associated with AEs leading to hospitalization.In total1884 reports related to SG were retrieved, and 114 AE signals involving 20 systems were identified. The median time for onset of AEs was around 6-7 days after initiating treatment with SG, with over 80% of AEs occurring within 30 days. Subgroup analysis revealed that 14 signals were reported in the males and 110 in the females. There were 58 signals reported in patients under 65 following the use of SG, 59 signals in patients over 65, and 31 signals were present in both groups. Multivariable analysis showed that the males and the occurrence of Colitis, Pneumonitis, Febrile Neutropenia, Pyrexia, Sepsis, Dehydration, and Diarrhea were risk factors leading to hospitalization with an AUC of 0.89. Additionally, sensitivity analysis revealed that this study had good robustness.This is the first retrospective analysis based on FAERS to review the safety of SG. The results highlight the need to closely monitor adverse reactions such as neutropenia, diarrhea, colitis, and sepsis when using SG.

8. 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] Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. This phase I trial evaluated this ADC as a potential therapeutic for pretreated patients with a variety of metastatic solid cancers.