Overview

PeRioperative Immunotherapy Combined With Sacituzumab Govitecan in Muscle Invasive blAdder Cancer

Status:
Not yet recruiting
Trial end date:
2030-12-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Fundación para el Progreso de la Oncología en Cantabria
Collaborator:
Apices Soluciones S.L.
Treatments:
Sacituzumab govitecan
Criteria
Inclusion Criteria:

1. Willing and able to provide written informed consent.

2. Ability to comply with the study procedures and requirements and restrictions in this
protocol.

3. Age ≥ 18 years.

4. 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.

5. Fit and planned for cystectomy (according to local guidelines).

6. 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).

7. 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.

8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

9. Adequate hematologic and end-organ function tests defined by the following:

1. White Blood Cell (WBC) ≥ 2.0x109/L,

2. Neutrophils ≥1.5x109/L,

3. Platelets ≥100 x109/L,

4. Hemoglobin ≥ 10 g/dL,

5. Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation

6. Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal(ULN),

7. Alanine aminotransferase (ALT) ≤2.5 x ULN,

8. Bilirubin ≤1.5 X ULN.

10. Adequate coagulation (Prothrombin Time [PT]) or International Normalized Ratio [INR]
and Activated Partial Thromboplastin Time [aPTT]) ≤ 1.5 x ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of
intended use of anticoagulants.

11. Negative pregnancy test within 3 days of Day 1 Cycle 1 for female patients of
childbearing potential.

12. Male patients and female patients of childbearing potential who engage in heterosexual
intercourse must agree to use protocol-specified method(s) of contraception.

Exclusion Criteria:

1. Concurrent enrollment in another interventional clinical trial, unless in a follow-up
period or it is an observational study.

2. Having received previous anticancer therapy including:

1. Any investigational anticancer therapy received within 28 days or 5 half-lives
(whichever is longer) of first dose of study treatment.

2. Any previous intravenous chemotherapy specific for bladder cancer.

3. Previous systemic treatment with topoisomerase 1 inhibitors.

4. Prior Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or Programmed death-1(PD-1)/
programmed death-ligand 1(PD-L)1-targeting immunotherapy.

5. Previous treatment with high dose chemotherapy and bone marrow transplant

6. Previous radiotherapy specific for bladder cancer

3. Underlying medical conditions that might make the administration of study drugs
hazardous or that might obscure the interpretation of adverse events including:

- 3.1 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.

- 3.2 History of primary immunodeficiency.

- 3.3 A positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic
acid (RNA), active tuberculosis, or other active infection requiring therapy at
the time of inclusion.

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.

4. Patient receiving treatment with inhibitors or inducers of UGT1A1 at the time of
enrollment.

5. Patient receiving treatment with high dose systemic corticosteroids (>10 mg of
prednisone or its equivalent) within 2 weeks of C1D1.

6. Patients who have received a vaccination within 30 days prior to inclusion (examples
include, but are not limited to, intranasal influenza vaccines, typhoid [oral]
vaccines, and Bacillus Calmette-Guerin [BCG]). Patients are allowed to receive the
COVID-19 vaccine to reduce the risk and complications of COVID-19 infection. The study
visits should continue as planned if vaccination occurs while the patient is on the
study.

7. Malignancy, other than urothelial cancer, in the previous 2 years. Patients with
low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and Prostatic
specific antigen (PSA) ≤ 10 ng/mL) appropriately treated or that are treatment-naive
and undergoing active surveillance are eligible. Also, noninvasive malignancies such
as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal
carcinoma in situ of the breast, that have undergone potentially curative therapy are
not excluded.

8. Major surgical procedure within 4 weeks prior to enrollment or anticipation of need
for a major surgical procedure during the course of the study other than for diagnosis
or treatment of its urothelial cancer.

9. Severe infection within 4 weeks prior to enrollment in the study including but not
limited to hospitalization for complications of infection, bacteremia, or severe
pneumonia.

10. Met any of the following criteria for cardiac disease:

1. Myocardial infarction or unstable angina pectoris within 6 months of enrollment.

2. History of serious ventricular arrhythmia (ie, ventricular tachycardia or
ventricular fibrillation), high-grade atrioventricular block, or other cardiac
arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation
that is well controlled with antiarrhythmic medication).

3. History of QT interval prolongation.

11. Patient currently on dialysis.

12. Gastrointestinal perforation within 6 months of enrollment.

13. Patients who have organ allografts.

14. Other concurrent medical or psychiatric conditions that, in the Investigator's
opinion, may be likely to confound study interpretation or prevent completion of study
procedures and follow-up examinations.

15. Known allergy or hypersensitivity to study drugs formulations.

16. Patients who have invasive catheters that under the investigator criteria might put
the patient at risk of developing severe complications due to neutropenia development.

17. Females who are pregnant, lactating, or intend to become pregnant during their
participation in the study.