Sacituzumab + Atezolizumab for Urologic Cancers

Overseen By Tzu-Fang Wang, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immune checkpoint therapies

Disqualifiers: Autoimmune disease, Brain metastases, Cardiovascular disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 11

Duration: Up to 5 years

60 Participants Needed

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. ^{1 2 3 4 5}

What 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. ^{2 3 4 6 7}

How 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. ^{1 2 5 8 9}

Research Team

Andrea B Apolo, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility 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 mostly self-sufficient and can carry out daily activities.

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.

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

Treatment Details

Interventions

• Atezolizumab
• Sacituzumab Govitecan

Trial Overview 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.

Participant Groups

Group I: Arm 2 Experimental Treatment 2 Interventions

Treatment with sacituzumab govitecan and atezolizumab

Group II: Arm 1 Experimental Treatment 1 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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq&#174;): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

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 (SG) is an effective treatment for locally advanced and metastatic urothelial cancer, showing a 27% objective response rate in the TROPHY-U-01 phase II trial.

While SG has common side effects like diarrhea and neutropenia, these can be managed with supportive care, and it has received accelerated approval for patients who have previously undergone platinum-based chemotherapy and PD-1 or PD-L1 inhibitor treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. Mathew Thomas, V., Tripathi, N., Agarwal, N., et al.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, 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]

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]

Atezolizumab showed some efficacy in patients with renal insufficiency, with objective response rates varying from 0% to 21% based on creatinine clearance levels, indicating potential benefits even in those with compromised kidney function.

The treatment was also effective in patients with mixed variant histology (MVH) urothelial carcinoma, showing a 33% response rate, while safety profiles were consistent across different patient subgroups, suggesting it can be safely administered to these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Hoffman-Censits, J., Pal, S., Kaiser, C., et al.[2021]

Atezolizumab, a PD-L1 targeting antibody, was found to be tolerable and effective in a real-world study involving 1004 patients with advanced urinary tract carcinoma, including those typically excluded from clinical trials.

The median overall survival for patients treated with atezolizumab was 8.7 months, with a 6-month survival rate of 60%, indicating that its efficacy aligns with previous clinical trial results, even in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Sternberg, CN., Loriot, Y., James, N., et al.[2020]

References

1. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq&#174;): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

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

Atezolizumab: First Global Approval. [2019]

3. 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]

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

Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma. [2022]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

6. 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]

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]

8. England pubmed.ncbi.nlm.nih.gov

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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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]