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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if two drugs, sacituzumab govitecan (SG) and atezolizumab (Tecentriq), can treat rare tumors in the urinary system, including the kidneys, bladder, ureters, and penis. Researchers will test SG alone or with atezolizumab to assess their effects on various types of these rare cancers. Individuals with unusual and aggressive forms of cancer in these areas, such as certain bladder or penile cancers, may be suitable for this trial. Participants will receive the treatments intravenously in cycles, with regular check-ups and tests to monitor progress. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that sacituzumab govitecan holds promise in treating various cancers, including breast and bladder cancers. Most patients tolerate it well, though some have experienced side effects such as low white blood cell counts and diarrhea. Monitoring these side effects is important, but they can be managed with care.

Atezolizumab, a medicine that helps the immune system fight cancer, is already approved for other cancers, indicating a well-understood safety profile. Common side effects include fatigue and some immune-related reactions, which are usually manageable.

Studies have examined the safety of combining sacituzumab govitecan and atezolizumab. The combination is generally considered tolerable, with reported side effects like low blood counts and diarrhea. These require monitoring but can typically be managed with medical support.

Overall, both treatments have been studied in patients and are known to have manageable safety profiles. Participants should discuss possible side effects and management strategies with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sacituzumab govitecan and atezolizumab for urologic cancers because these treatments offer a novel approach compared to current options like chemotherapy or surgery. Sacituzumab govitecan is an antibody-drug conjugate that specifically targets cancer cells with a unique mechanism by delivering chemotherapy directly to the tumor, potentially reducing side effects. Atezolizumab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells more effectively. Together, these treatments might enhance the body's ability to fight cancer while minimizing damage to healthy cells, offering new hope for patients with urologic cancers.

What evidence suggests that this trial's treatments could be effective for rare GU tumors?

Research has shown that sacituzumab govitecan (SG), which participants in this trial may receive, can be effective in treating advanced bladder cancer. Studies have found that about 27% of patients respond to SG, with an average survival time of around 10.9 months, surpassing some standard treatments. In this trial, some participants will receive SG alone, while others will receive a combination of SG and atezolizumab. Early research in different cancers suggests that combining SG with atezolizumab might enhance effectiveness, particularly for certain types like PD-L1-positive breast cancer. Atezolizumab alone has demonstrated a 23% response rate in some cancers and an average survival time of 15.9 months. These findings suggest that combining SG and atezolizumab could benefit the treatment of rare urologic cancers. ^{4 6 7 8 9}

Who Is on the Research Team?

Andrea B Apolo, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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, 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39934055/

Sacituzumab govitecan in advanced urothelial carcinoma Conclusions: SG did not result in a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00015-8/fulltext

Sacituzumab govitecan in advanced urothelial carcinoma Median PFS with SG and TPC was 4.2 months and 3.6 months, respectively (HR 0.86, 95% CI 0.72-1.03); ORR (95% CI) was 23% (18% to 27%) and 14% ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8315301/

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab ... The ORR of 27%, median duration of response of 7.2 months, and median overall survival of 10.9 months compare favorably with single-agent chemotherapy in this ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4591

First survival outcomes and biomarker results of SURE-01 Results: From 03/22 to 01/25, 37 pts were enrolled and 33 were efficacy-evaluable. Median age was 71y and 16 pts (48.5%) had cT3-4N0 stage.

5. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-bladder-cancer/160789-asco-2025-first-results-of-sure-02-a-phase-2-study-of-neoadjuvant-sacituzumab-govitecan-pembrolizumab-followed-by-response-adapted-bladder-sparing-and-adjuvant-pembrolizumab-in-patients-with-mibc.html

ASCO 2025: First Results of SURE-02: A Phase 2 Study ... Perioperative sacituzumab govitecan + pembrolizumab revealed a compelling clinical complete response rate (44%), with a manageable safety ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01631552

Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults ... Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10587566/

Assessing real-world safety concerns of Sacituzumab govitecan Sacituzumab govitecan (SG) is a novel ADC, which exhibits promising results for the treatment of solid tumors, including breast cancer and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11554802/

Efficacy and safety of sacituzumab govitecan Trop-2- ... Other cancers refer to ovarian, gastric cancer, UBC, NSCLC, HRPC, esophaegeal adenocarcinoma, RCC, squamous cell carcinoma of the tonsil. b ...

9. onclive.com onclive.com/view/sacituzumab-govitecan-does-not-significantly-improve-os-in-pretreated-urothelial-carcinoma

Sacituzumab Govitecan Does Not Significantly Improve ... Sacituzumab govitecan did not significantly improve OS or PFS over chemotherapy in advanced urothelial carcinoma patients. The antibody-drug ...