PeRioperative Immunotherapy Combined With Sacituzumab Govitecan in Muscle Invasive blAdder Cancer

NCT06133517 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: PRISMA-12023-504420-26-00
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 6

Brief Summary

The main objective of this trial is to evaluate the efficacy of the combo Sacituzumab govitecan (SG) + Zimberelimab (AB 122) (ZIM) + Domvanalimab (AB 154) (DOM), measured as pathologic complete response (pCR) rates, in the perioperative setting in patients with Muscle Invasive Bladder Cancer (MIBC) who are either unfit for platinum-based chemotherapy or unwilling to receive that therapy.

Conditions

Urothelial Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy measured as pathologic complete response rates of the combo SG+ZIM+DOM in the perioperative setting in patients with MIBC who are either unfit for platinum-based chemotherapy or unwilling to receive that therapy.

  Efficacy of the combination of sacituzumab govitecan, zimberelimab and domvanalimab measured as pathologic complete response (pCR) rates. pCR is defined as absence of residual viable tumor (ypT0) in the radical cystectomy specimen and in the resected lymph nodes (ypN0) (post-treatment).

  42 months

Secondary Outcomes (6)

• To evaluate the downstaging rate induced by the combo

  42 months

• To measure overall survival (OS) and disease-free survival (DFS) in the study population

  42 months

• To evaluate the safety of the combo

  42 months

• To identify predictive biomarkers associated with response to SG + ZIM + DOM.

  42 months

• To gain knowledge about the role of ctDNA in the perioperative setting

  42 months

Study Arms (1)

Single Arm

EXPERIMENTAL

Patients who are eligible to participate in the study will receive 3 cycles of sacituzumab govitecan, zimberelimab and domvanalimab every 3 weeks prior to cystectomy, unless there are signs of unacceptable toxicity, progressive disease, or the patient requests withdrawal from the study. Patients who do not achieve a pCR or that achieving a pCR still have positive ctDNA will also complete an adjuvant phase of the study consisting of 12 additional cycles of zimberelimab and domvanalimab after cystectomy.

Drug: Sacituzumab govitecan; Drug: Zimberelimab; Drug: Domvanalimab

Interventions

Sacituzumab govitecan DRUG

Sacituzumab govitecan is administered at 10 mg/kg as an intravenous (IV) infusion on Days 1 and 8 of a 21-day cycle.

Also known as: Trodelvy

Single Arm

Zimberelimab DRUG

ZIM is administered at 360 mg every 3 weeks as an intravenous (IV) infusion on Day 1 of a 21-day cycle.

Single Arm

Domvanalimab DRUG

DOM is administered at 1200 mg every 3 weeks as an intravenous (IV) infusion on Day 1 of a 21-day cycle.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent.
• Ability to comply with the study procedures and requirements and restrictions in this protocol.
• Age ≥ 18 years.
• Muscle invasive urothelial carcinoma stage cT2-T4cN0-1cM0. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) urothelial carcinoma pattern.
• Fit and planned for cystectomy (according to local guidelines).
• Refusal of neoadjuvant cisplatin-based chemotherapy or patients in whom neoadjuvant cisplatin-based therapy is not appropriate. (This will be determined by the investigator and not solely based in Galsky Criteria).
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site. Patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with the PI of the study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Adequate hematologic and end-organ function tests defined by the following:
• White Blood Cell (WBC) ≥ 2.0x109/L,
• Neutrophils ≥1.5x109/L,
• Platelets ≥100 x109/L,
• Hemoglobin ≥ 10 g/dL,
• Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation
• Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal(ULN),

You may not qualify if:

• Concurrent enrollment in another interventional clinical trial, unless in a follow-up period or it is an observational study.
• Having received previous anticancer therapy including:
• Any investigational anticancer therapy received within 28 days or 5 half-lives (whichever is longer) of first dose of study treatment.
• Any previous intravenous chemotherapy specific for bladder cancer.
• Previous systemic treatment with topoisomerase 1 inhibitors.
• Prior Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or Programmed death-1(PD-1)/ programmed death-ligand 1(PD-L)1-targeting immunotherapy.
• Previous treatment with high dose chemotherapy and bone marrow transplant
• Previous radiotherapy specific for bladder cancer
• Underlying medical conditions that might make the administration of study drugs hazardous or that might obscure the interpretation of adverse events including:
• Known or suspected autoimmune disease. Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) are excluded from this study; Patients with other autoimmune disorders such as a history of Hashimoto's thyroiditis \[only requiring hormone replacement\], type I diabetes, psoriasis \[not requiring systemic treatment\], or conditions not expected to recur in the absence of an external trigger are allowed to participate.
• History of primary immunodeficiency.
• HIV positive patients are allowed as far as they have the disease controlled according to their treating physicians based on lymphocyte counts and viral load.
• \- 3.4 Medical conditions requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) will be allowed.
• Patient receiving treatment with inhibitors or inducers of UGT1A1 at the time of enrollment.
• Patient receiving treatment with high dose systemic corticosteroids (\>10 mg of prednisone or its equivalent) within 2 weeks of C1D1.

Sponsors & Collaborators

• Fundación para el Progreso de la Oncología en Cantabria: lead
• Apices Soluciones S.L.: collaborator

Study Sites (6)

Hospital Duran i Reynals (ICO L´Hospitalet)

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Location

Hospital Universitario de Navarra

Pamplona, Navarre, Spain

Location

Hospital Virgen de la Salud

Toledo, Toledo, Spain

Location

Hospital Clinico Universitario de Valladolid

Valladolid, Valladolid, Spain

Location

MeSH Terms

Interventions

sacituzumab govitecan; zimberelimab

Study Officials

• Ignacio Duran, MD

  Hospital Universitario Marqués de Valdecilla

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2023
• First Posted: November 15, 2023
• Study Start: January 20, 2025
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 16, 2026

Record last verified: 2025-03

Locations

ES (6)