Sacituzumab + Atezolizumab for Urologic Cancers
Recruiting in Palo Alto (17 mi)
Overseen byAndrea B Apolo, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Immune checkpoint therapies
Disqualifiers: Autoimmune disease, Brain metastases, Cardiovascular disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?Background:
Rare tumors of the genitourinary (GU) tract can appear in the kidney, bladder, ureters, and penis. Rare tumors are difficult to study because there are not enough people to conduct large trials for new treatments. Two drugs-sacituzumab govitecan (SG) and atezolizumab-are each approved to treat other cancers. Researchers want to find out if the two drugs used together can help people with GU.
Objective:
To test SG, either alone or combined with atezolizumab, in people with rare GU tumors.
Eligibility:
Adults aged 18 years and older with rare GU tumors. These may include high grade neuroendocrine carcinomas; squamous cell carcinoma of the bladder; primary adenocarcinoma of the bladder; renal medullary carcinoma; or squamous cell carcinoma of the penis.
Design:
Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of heart function. They will have imaging scans. They may need a biopsy: A small needle will be used to remove a sample of tissue from the tumor.
Both SG and atezolizumab are given through a tube attached to a needle inserted into a vein in the arm.
All participants will receive SG on days 1 and 8 of each 21-day treatment cycle. Some participants will also receive atezolizumab on day 1 of each cycle.
Blood and urine tests, imaging scans, and other exams will be repeated during study visits.
Treatment may continue for up to 5 years.
Follow-up visits will continue for 5 more years.
...
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) for prior treatments like chemotherapy, radiotherapy, and certain immunosuppressive medications before starting the trial. It's best to discuss your current medications with the study team to understand any potential interactions.
What data supports the effectiveness of the drug combination Sacituzumab Govitecan and Atezolizumab for urologic cancers?
Atezolizumab has shown effectiveness in treating advanced bladder cancer, with response rates of up to 24% and improved survival in patients who are not eligible for certain chemotherapies. Sacituzumab Govitecan has also demonstrated preliminary activity in patients with metastatic urothelial carcinoma, offering a potential option for those who have limited treatment choices.
12345What safety information is available for Sacituzumab Govitecan and Atezolizumab?
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), with most adverse events occurring within 30 days of treatment. Atezolizumab has been approved for use in certain cancers, indicating it has undergone safety evaluations, but specific side effects are not detailed in the provided research.
23467How is the drug combination of Sacituzumab and Atezolizumab unique for treating urologic cancers?
This treatment combines Sacituzumab Govitecan, which delivers chemotherapy directly to cancer cells, with Atezolizumab, an immune therapy that helps the body's immune system attack cancer cells. This dual approach is novel because it targets cancer cells directly while also enhancing the immune response, potentially offering a more effective treatment for urologic cancers compared to existing options.
12589Eligibility Criteria
Adults over 18 with rare genitourinary tumors like small cell carcinoma of the bladder, squamous cell carcinoma of the bladder or penis, primary adenocarcinoma of the bladder, and renal medullary carcinoma. They must have measurable disease progression if previously treated, good physical function (ECOG <=1), adequate organ/marrow function, may have had any number of prior treatments or be treatment-naive.Inclusion Criteria
Pre-study treatment tissue availability (sufficient tissue for approximately 25 unstained slides is mandatory for enrollment)
Ability of participants to understand and the willingness to sign a written informed consent document
I am 18 years old or older.
+11 more
Exclusion Criteria
I have brain metastases that are causing symptoms or have not been treated.
I am unwilling to receive blood products even if needed for my treatment.
I have or had an autoimmune disease or immune deficiency.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive sacituzumab govitecan on days 1 and 8 of each 21-day cycle, with some also receiving atezolizumab on day 1
Up to 5 years
Visits on days 1 and 8 of each 21-day cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Every 9 weeks during follow-up
Participant Groups
The trial is testing Sacituzumab Govitecan (SG) alone or combined with Atezolizumab in treating rare GU cancers. Participants will receive SG on specific days within a 21-day cycle; some will also get Atezolizumab. The study includes regular blood/urine tests and scans for up to 5 years with an additional follow-up period.
2Treatment groups
Experimental Treatment
Group I: Arm 2Experimental Treatment2 Interventions
Treatment with sacituzumab govitecan and atezolizumab
Group II: Arm 1Experimental Treatment1 Intervention
Treatment with sacituzumab govitecan
Atezolizumab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
🇪🇺 Approved in European Union as Tecentriq for:
- Melanoma
- Hepatocellular carcinoma
- Small cell lung cancer
- Non-small cell lung cancer
- Urothelial carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq®) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.
Atezolizumab: First Global Approval. [2019]Atezolizumab (Tecentriq™)-a monoclonal antibody targeting programmed death ligand 1 (PD-L1 or CD274 antigen)-is being developed by Genentech as treatment for a variety of haematological malignancies and solid tumours. It been approved in the US as a second-line therapy for urothelial carcinoma and is awaiting approval as a second-line therapy for non-small cell lung cancer. This article summarizes the milestones in the development of atezolizumab leading to this first approval for urothelial carcinoma.
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.
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.
Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]Atezolizumab (Tecentriq, MPDL3280A; Genentech/Roche) is an FcγR binding-deficient, fully humanized IgG1 mAb designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironment and, consequently, increases T-cell-mediated immunity against the tumor. Atezolizumab has been FDA approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase II trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses. In subjects whose tumors progressed on first-line platinum-based chemotherapy, the objective response rate was 15%, the complete response rate was 5%, and 1-year overall survival was 36%. In subjects that were chemotherapy naïve and cisplatin ineligible, the objective response rate was 24%, the complete response rate was 7%, and 1-year overall survival was 57%. Better responses were associated with higher PD-L1 expression on the tumor-infiltrating leukocytes. These data suggest that patients with advanced bladder cancer treated with atezolizumab have significantly better response rates and survival than historical controls treated with other second-line regimens. The toxicity profile of atezolizumab is also favorable. Trials are currently assessing whether atezolizumab is effective in earlier bladder cancer stages and in the first-line metastatic setting. Clin Cancer Res; 23(8); 1886-90. ©2016 AACR.
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.
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.
Atezolizumab in patients with renal insufficiency and mixed variant histology: analyses from an expanded access program in platinum-treated locally advanced or metastatic urothelial carcinoma. [2021]Atezolizumab is a treatment for locally advanced/metastatic urothelial carcinoma (mUC). However, its use in patients with renal insufficiency or UC with mixed variant histology (MVH) is not well characterized.
Primary Results from SAUL, a Multinational Single-arm Safety Study of Atezolizumab Therapy for Locally Advanced or Metastatic Urothelial or Nonurothelial Carcinoma of the Urinary Tract. [2020]Atezolizumab, a humanised monoclonal antibody targeting PD-L1, is approved for locally advanced/metastatic urothelial carcinoma. SAUL evaluated atezolizumab in a broader, pretreated population, including patients ineligible for the pivotal IMvigor211 phase 3 trial of atezolizumab.