Adjuvant Sacituzumab Govitecan and Nivolumab in Muscle-Invasive Urothelial Carcinoma at High-Risk Recurrence

Adjuvant Sacituzumab Govitecan Plus Nivolumab in Patients With Muscle-Invasive Urothelial Carcinoma at High-Risk for Recurrence

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.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma; Muscle-invasive Bladder Cancer
• Intervention / Treatment: Drug: Nivolumab; Drug: Sacituzumab Govitecan (SG)

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chao Family Comprehensive Cancer Center University of California, Irvine; Phone Number: 1-877-827-8839; Email: ucstudy@uci.edu
• Study Contact Backup: Name: University of California Irvine Medical

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Chao Family Comprehensive Cancer Center, University of California, Irvine
      • Contact: Nataliya Mar, MD; Phone Number: 877-827-8839; Email: ucstudy@uci.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years at the time of study consent.
• ECOG Performance Status of 0, 1 or 2 (see Appendix A).
• Histologically confirmed muscle-invasive UC originating in the bladder, ureter, or renal pelvis. Variant histology, except small cell carcinoma, is allowed.
• Underwent curative-intent surgery (i.e. RC or nephroureterectomy), performed within 180 days prior to study treatment initiation.
• Radiographic disease-free status as determined by imaging within 28 days of C1D1 of study treatment.
• Prior platinum-based NAC is allowed. If chemotherapy-naive, patient must be Cisplatin-ineligible (based on Galsky et al 2011 [10]) or refuse platinum AC.
• Prior treatment with neoadjuvant investigational agents is allowed (except PD-1/PD-L1 inhibitors or sacituzumab govitecan). No washout from neoadjuvant therapy is required.
• If NAC was given, patient must be considered at high risk for cancer recurrence due to having pathologic T2, T3, T4, or N+ disease on RC or nephroureterectomy surgical spec-imen.
• If no NAC was given, patient must be considered at high risk for cancer recurrence due to having pathologic T3, T4, or N+ disease on RC or nephroureterectomy surgical speci-men.
• Adequate organ and marrow function as defined below:
• ANC ≥ 1000/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 × institutional ULN (or ≤ 3.0 × ULN for subjects with Gilbert's disease)
• AST/ALT ≤ 3 × institutional ULN
• Alkaline phosphatase ≤ 3 × institutional ULN
• Serum albumin ≥ 2.8 g/dL
• Creatinine Creatinine clearance of ≥30 mL/min (calculated with Cockroft-Gault formula)
• Hemoglobin ≥ 9.0 g/dL
• aPTT ≤ 1.5 × institutional ULN
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (i.e. barrier methods including male condom, female condom, or diaphragm with spermicidal gel, etc.) that are approved by the Investigator. Contra-ception must be used during the course of the treatment and for 6 months after the last dose of study treatment.
• Female subjects of childbearing potential must not be pregnant following signing the study consent form. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal sta-tus (defined as at least 12 months of amenorrhea in a woman ≥ 45 years-of-age in the ab-sence of other biological or physiological causes).
• Recovery to ≤ Grade 1 of CTCAE version 5 toxicities related to any prior treatment for UC, unless the AE(s) is clinically non-significant and/or stable on supportive therapy as per discretion of the Investigator.
• Subjects with any type of genitourinary catheters (i.e. nephrostomy, Foley, etc) are al-lowed.
• Ability to understand and the willingness to sign a written informed consent. Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, hard of hearing, and illiterate individuals are eligible for this trial.

Exclusion Criteria

• Underwent a partial cystectomy or partial nephrectomy.
• History of adjuvant platinum-based chemotherapy or any other type of adjuvant therapy, including investigational agents, following surgical removal of UC.
• History of treatment with PD-1/PD-L1 inhibitors or sacituzumab govitecan prior to study treatment initiation.
• History of previous radiation therapy for treatment of UC.
• Radiographic evidence of metastasis.
• Receipt of or planning to receive any other concurrent investigational agents.
• History of active, known, or suspected autoimmune disease.
• Conditions requiring treatment with either systemic high-dose corticosteroids (e.g. prednisone dose of ≥ 10 mg or equivalent) or other immunosuppressive medications within 14 days of study treatment initiation.
• Inhaled or topical steroids are permitted in the absence of active autoimmune dis-ease.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Major surgery within 28 days or minor surgery within 14 days before the first dose of study treatment. Subjects must have complete wound healing and resolution from complications of major or minor surgery before first dose of study treatment.
• Active malignancy within 3 years of study entry, except treated localized non-melanoma skin cancer, Gleason 6 prostate cancer on active surveillance, or curatively treated in situ cancer of the breast or cervix.
• Patients who do not have adequate organ and marrow function, as defined in Section 4.1 above.
• Uncontrolled intercurrent illness including, but not limited to, the following conditions:
• Active and/or uncontrolled bacterial, viral, or fungal infection within 7 days of study treatment initiation.
• History of HIV infection with detectable viral load.
• History of Hepatitis B or C infection with detectable viral load.
• History of severe liver impairment (Child-Pugh C liver cirrhosis).
• History of active tuberculosis (Bacillus tuberculosis).
• Congestive heart failure New York Heart Association (NYHA) Class 3 or 4, unstable angina pectoris, or serious uncontrolled cardiac arrhythmias.
• Stroke (including transient ischemic attack (TIA), myocardial infarction (MI), or other ischemic arterial event within 90 days before first dose of study treatment.
• Severe, uncontrolled bleeding within 14 days before first dose of study treatment.
• Uncontrolled diarrheal illness ≥ Grade 3 in severity within 14 days before first dose of study treatment.
• History of inflammatory bowel disease (i.e. ulcerative colitis, Crohn's disease, etc.) or any other condition that puts patients at high risk of developing severe diarrhea.
• Psychiatric illness/social situations causing inability to comply with study proce-dures or follow up.
• Pregnancy at the time of or following study consent.
• Breastfeeding at the time of or following study consent.
• Received a live vaccine within 28 days prior to the first dose of study treatment.
• Known or suspected severe hypersensitivity (Grade ≥ 3) to nivolumab, sacituzumab govitecan, irinotecan, and/or any of their components.
• History or current evidence of any condition, therapy, or laboratory/radiographic abnormal-ity that might confound the results of the study, interfere with the patient's ability to participate for the full duration of the study, or is not in the best interest of the patient to partici-pate in the study, in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacituzumab Govitecan PLUS Nivolumab; 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.	Drug: Nivolumab; Given IV; Drug: Sacituzumab Govitecan (SG); Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Objective	To determine investigator-assessed disease-free survival (DFS) at 6 months.	6 months after last patient enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary (1)	To determine investigator-assessed DFS (i.e. time from Cycle 1 Day 1 (C1D1) of study treatment to first occurrence of a DFS event), defined as any of the following: Local (pelvic) recurrence of UC (including regional lymph nodes); Urinary tract recurrence of UC (including all pathological stages and grades); Distant metastasis of UC; Death from any cause	Time from Cycle1 Day 1 of study treatment to first occurrence of a disease free survival event, up to 5 years.
Secondary (2)	To determine investigator-assessed distant metastasis-free survival (MFS) (i.e. time from Cycle 1 Day 1 of study treatment to diagnosis of distant metastases or death from any cause).	Time from Cycle 1 Day 1 of study treatment to diagnosis of distant metastases or death from any cause, up to 5 years.
Secondary (3)	To determine overall survival (OS) (i.e. time from Cycle 1 Day 1 of study treatment to death of any cause).	Time from C1D1 of study treatment to death of any cause, up to 5 years.
Secondary (4)	To determine incidence of Grade 3 or higher AEs.	Up to 5 years
Secondary (5)	To determine rate of ctDNA clearance in ctDNA positive patients (i.e. conversion from positive ctDNA to negative at any point from baseline assessment).	Conversion from positive ctDNA to negative at any point from baseline assessment, up to 5 years.
Secondary (6)	To perform exploratory biomarker analysis.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: Gilead Sciences
• Investigators: Principal Investigator: Nataliya Mar, MD, Chao Family Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 1, 2024
• First Submitted That Met QC Criteria: November 8, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma; nivolumab; UC; sacituzumab govitecan; MIBC; muscle-invasive urothelial carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; sacituzumab govitecan
• Other Study ID Numbers: 4473; UCI 23-59 (Other Identifier: UCI CFCCC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes