Sacituzumab Govitecan Before Radical Cystectomy for the Treatment of Non-Urothelial Muscle Invasive Bladder Cancer

NCT05581589 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1122399NCI-2022-0452810996
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests whether sacituzumab govitecan given before radical cystectomy works in treating patients with non-urothelial bladder cancer. Sacituzumab govitecan contains a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers govitecan to kill them. Giving sacituzumab govitecan before radical cystectomy may make the surgery more effective in patients with muscle invasive bladder cancer.

Conditions

Muscle Invasive Bladder Carcinoma; Stage II Bladder Cancer AJCC v8; Stage IIIA Bladder Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR Defined as ypT0N0)

  Percentage of patients with no histologic evidence of tumor at time of cystectomy (ypT0N0)

  At radical cystectomy (Radical cystectomy is expected to occur within 2-6 weeks after the last neoadjuvant trial therapy dose)

Secondary Outcomes (5)

• Recurrence-free Survival at the 2-year Time Point

  Up to 2 years from time of study enrollment

• Overall Survival (OS) at the 2-year Time Point

  Up to 2 years from time of study enrollment

• Frequency of Any Adverse Event According to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) Related to Study Therapy.

  Up to 2 years from time of study enrollment

• Frequency of Grade 3 or Greater Adverse Events According to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) Related to Study Therapy.

  Up to 2 years from time of study enrollment

• Pathologic Downstaging to <ypT2N0 at Time of Radical Cystectomy

  At radical cystectomy (radical cystectomy occured within 6 weeks after the last neoadjuvant trial therapy dose)

Study Arms (1)

Treatment (sacituzumab govitecan)

EXPERIMENTAL

Patients receive sacituzumab govitecan IV over 3 hours on days 1 and 8 of each cycle. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks after last dose, patients undergo radical cystectomy and pelvic lymph node dissection.

Procedure: Lymphadenectomy; Procedure: Radical Cystectomy; Biological: Sacituzumab Govitecan

Interventions

Lymphadenectomy PROCEDURE

Undergo pelvic lymph node dissection

Also known as: excision of the lymph node, Lymph Node Dissection, Lymph Node Excision

Treatment (sacituzumab govitecan)

Radical Cystectomy PROCEDURE

Undergo radical cystectomy

Also known as: Complete Cystectomy

Treatment (sacituzumab govitecan)

Sacituzumab Govitecan BIOLOGICAL

Given IV

Also known as: hRS7-SN38 Antibody Drug Conjugate, IMMU-132, RS7-SN38, Sacituzumab Govitecan-hziy, Trodelvy

Treatment (sacituzumab govitecan)

Eligibility Criteria

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

You may qualify if:

• Participants must be at least 18 years of age on the day of signing informed consent. Participant (or legally acceptable representative if applicable) provides written informed consent for trial
• Participants must have either histologically or by clinical consensus (based on imaging and/or exam under anesthesia) confirmed diagnosis of muscle invasive bladder cancer (cT2-T4aN0-N1M0 or cT1-4aN1M0 clinical stage per American Joint Commission on Cancer \[AJCC\]). Patients with clinical node-positive (N1) stage are eligible provided the lymph node (LN) is confined to the true pelvis and is within the planned surgical LN dissection template; cN1 is defined as a lymph node with \>= 15 mm short axis or biopsy-positive for carcinoma
• Must have clinical non-metastatic bladder cancer (M0) determined by cross-sectional Computed tomography (CT) chest, abdomen and pelvis (CAP) or magnetic resonance imaging (MRI)
• Review of pathology by local expert genitourinary (GU) pathologist is required. Any component (%) of non-conventional urothelial (variant histology) noted on transurethral resection of bladder tumour (TURBT) is allowed, for histologic types not listed below. However, for the variant histologic types listed below, the following parameters need to be met:
• Squamous cell carcinoma / squamous cell features need to be pure or predominant (\>= 1 variant histologic with total non-conventional urothelial component \> 50%).
• Adenocarcinoma / glandular features need to be pure or predominant (\>= 1 variant histologic total non-conventional urothelial component \> 50%).
• Any % of neuroendocrine / small cell histology is excluded.
• Patients must be considered unfit for cisplatin based on the Galsky et al. criteria or refuse cisplatin despite adequate counseling in cisplatin-fit patients. Especially, for tumors containing squamous cell or glandular features, every effort should be made to discuss the benefit of neoadjuvant cisplatin-based chemotherapy shown in the S8710 trial
• Participants must be deemed eligible for radical cystectomy (RC) and pelvic lymph node dissection (PLND) by both urologist and medical oncologist
• TURBT that showed muscularis propria (or lamina propria for cT1N1 tumors) invasion should be within 12 weeks prior to beginning study therapy. Patients must have available tumor tissue from either initial or repeat TURBT, prior to starting study therapy. Archival and/or fresh tumor tissue sample of a tumor lesion (TURBT specimen) should be provided and must contain muscle invasive component, at least \>= T2 tumor (for cT2 tumors), unless clinical stage is cT1N1M0 (in that case muscle invasive component is not necessary). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory, preferably within 14 days from the date slides are cut if possible. Patient must be willing to provide tumor tissue for research. Research samples will not be used for unrelated studies
• A male participant must agree to use a contraception during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Patients with ECOG PS 2 may be permitted only after discussion with the trial primary investigator (PI) (Dr. Grivas). Evaluation of ECOG PS is to be performed within 7 days prior to the date of enrollment.

You may not qualify if:

• Patients with any % of neuroendocrine / small cell histology
• Patients considered to be medically unfit for SG, TURBT or radical cystectomy (per investigator discretion)
• Prior systemic anti-cancer therapy, including investigational agent/device within 4 weeks or prior radiation therapy within 2 weeks. Intravesical therapies are allowed without specified treatment interval
• Known locally advanced (unresectable, e.g. cT4b) or metastatic (cN2-3, M1) cancer on baseline radiographic imaging (CT or MRI) obtained within 28 days prior to registration
• Active infection requiring systemic antibiotic therapy at the time of trial initiation. Human immunodeficiency virus (HIV)-positive patients on active therapy are eligible as long as their viral load is undetectable and CD4 count is within normal parameters during the time of trial therapy initiation
• Known history of active hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] detected or positive hepatitis B virus \[HBV\] polymerase chain reaction \[PCR\] test) or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA) \[qualitative\] detected) infection. Note: no testing for hepatitis B and hepatitis C is required if there is no clinical suspicion of such infection
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Known personality, psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
• Patients may not have concurrent upper urinary tract (i.e., ureter, renal pelvis) invasive urothelial carcinoma. Patients with history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that have been definitively treated with at least one post-treatment disease assessment (i.e., cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible. Previously treated or concurrent non-invasive (Ta, Tis) urethra carcinoma is allowed, but history of or concurrent invasive urethra carcinoma is excluded
• Patients may not have another malignancy that could interfere with the evaluation of safety or efficacy of of SG. Patients with prior malignancy will be allowed without PI approval in the following circumstances:
• Not currently active and completed therapy at least 2 years prior to the date of registration.
• Non-invasive cancer, such as low risk cervical cancer or any carcinoma in situ.
• Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy), and in which no systemic chemotherapy was indicated (e.g., low/intermediate risk prostate cancer, non-melanoma skin cancer, etc.). Low/intermediate risk prostate cancer on active surveillance or watchful waiting is allowed. Other cancers not meeting these criteria must be discussed with trial PI (Dr. Grivas)
• Patients may not have undergone major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =\< 3 weeks prior to starting SG, or who have not recovered from side effects of such procedure or injury
• Have active (based on symptoms, endoscopic or biopsy findings) chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) at time of trial therapy initiation or history of GI perforation within 6 months of enrollment

Sponsors & Collaborators

• University of Washington: lead
• Gilead Sciences: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Lymph Node Excision; Cystectomy; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Results Point of Contact

• Title: Dr. Petros Grivas
• Organization: University of Washington

pgrivas@uw.edu

2066061943

Study Officials

• Petros Grivas

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 14, 2022
• Study Start: June 15, 2023
• Primary Completion: October 15, 2024
• Study Completion: March 6, 2026
• Last Updated: April 27, 2026
• Results First Posted: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)