Sacituzumab Govitecan With or Without Atezolizumab Immunotherapy in Rare Genitourinary Tumors (SMART) Such as High Grade Neuroendocrine Carcinomas, Adenocarcinoma, and Squamous Cell Bladder/Urinary Tract Cancer, Renal Medullary Carcinoma and Penile C...

NCT06161532 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001535001535-C
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of the Bladder; Primary Adenocarcinoma of the Bladder; Primary Adenocarcinoma of the Urinary Tract; Squamous Cell Carcinoma of the Penis; Small Cell Carcinoma of the Bladder; Small Cell Carcinoma of the Urinary Tract; Renal Medullary Carcinoma; Squamous Cell Carcinoma of the Urinary Tract

Keywords

Urothelial carcinoma; Trophoblastic cell surface antigen 2; Programmed death-ligand 1; SN-38; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy

  On days 1 and 8 of each cycle and at every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD.

Secondary Outcomes (5)

• Duration of response (DoR)

  On days 1 and 8 of each cycle and at every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD.

• Overall survival (OS)

  Days 1 and 8 of each cycle, at EoT, at the Safety visit, at follow-up, and every 90 days for up to a total of 5 years after the end of therapy

• Progression-free survival (PFS)

  At every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD

• Clinical benefit rate (CBR)

  At every restaging (every 9 weeks) until the end of the study therapy and every 9 weeks during follow-up until PD

• Safety of sacituzumab govitecan with or without atezolizumab

  From first dose through 30 days after last treatment

Study Arms (2)

Arm 1

EXPERIMENTAL

Treatment with sacituzumab govitecan

Drug: Sacituzumab govitecan

Arm 2

EXPERIMENTAL

Treatment with sacituzumab govitecan and atezolizumab

Drug: Sacituzumab govitecan; Drug: Atezolizumab

Interventions

Sacituzumab govitecan DRUG

Sacituzumab govitecan is administered IV at 10 mg/kg on days 1 and 8 of each 21-day cycle.

Arm 1; Arm 2

Atezolizumab DRUG

Atezolizumab is administered IV at 1200 mg on day 1 each 21-day cycle.

Arm 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed diagnosis of a locally advanced unresectable or metastatic non-prostate genitourinary (GU) tumor of the following histologies:
• HGNEC, including, but not limited to, small cell carcinoma and large cell neuroendocrine carcinoma of the bladder or urinary tract
• Squamous cell carcinoma of the bladder or urinary tract
• Primary adenocarcinoma of the bladder or urinary tract (urachal or non-urachal)
• Renal medullary carcinoma
• Squamous cell carcinoma of the penis
• Note: For the purposes of enrollment, the urinary tract is defined as the renal pelvis, ureter, bladder, and urethra.
• Pre-study treatment tissue availability (sufficient tissue for approximately 25 unstained slides is mandatory for enrollment. If tissue is determined to be insufficient/unsuitable, a fresh biopsy prior to study therapy will be required.
• Locally advanced unresectable or metastatic disease. Participants who have received prior treatment must have evidence of progressive disease (PD; i.e., defined as new or progressive lesions evident on cross-sectional imaging).
• Prior treatment as follows:
• Cohort A: Participants must have received prior ICIs (PD-1 or PD-L1) or be ineligible for treatment with ICIs.
• For Cohort B: Participants must be ICI naive but eligible to receive them.
• Participants must have measurable disease, per RECIST 1.1.
• Age \>= 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky \>= 70%.

You may not qualify if:

• History of severe hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to SG, SN-38, irinotecan, or atezolizumab, or hypersensitivity to Chinese hamster ovary cell products.
• Symptomatic or untreated brain/CNS metastases.
• Positive serum or urine Beta-human chorionic gonadotropin (Beta-hCG) test at screening.
• Participants unwilling to accept blood products as medically indicated.
• For Cohort B: Active or history of autoimmune disease or immune deficiency that might recur, which might affect vital organ function or require immune suppressive treatment including systemic corticosteroids, when receiving atezolizumab. These conditions include myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Anticipation of need for a major surgical procedure during the study.
• Prior allogeneic stem cell or solid organ transplantation.
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during SG or atezolizumab treatment or within 5 months after the final dose of SG or atezolizumab. Note: Seasonal flu vaccines that do not contain a live virus and locally authorized/approved COVID-19 vaccines are permitted.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (1)

• Kydd AR, Chandran E, Simon NI, Atiq S, Ley L, Wang TF, Cordes L, Patel R, Smith E, Boudjadi S, Niglio SA, Yousefi-Rad A, Weng S, Stukes I, Banday AR, Akbulut D, Gurram S, Redd B, Steinberg S, Choo-Wosoba H, Apolo AB. A phase 2 study of sacituzumab govitecan with or without atezolizumab in rare genitourinary tumors (SMART) - design and rationale. Future Oncol. 2025 Aug;21(18):2261-2268. doi: 10.1080/14796694.2025.2516901. Epub 2025 Jun 23.

  PMID: 40548513 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

sacituzumab govitecan; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tzu-Fang Wang, R.N.

CONTACT

(240) 858-3236; tzu-fang.wang@nih.gov

Andrea B Apolo, M.D.

CONTACT

(301) 480-0536; apoloab@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2023
• First Posted: December 8, 2023
• Study Start: August 1, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-03-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers at least 3 years after the completion of the primary endpoint.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)