Durvalumab Plus Tremelimumab With Concurrent Radiotherapy for Localized Muscle Invasive Bladder Cancer Treated With a Selective Bladder Preservation Approach

Inclusion Criteria

• Patients must have signed the informed consent prior to undergoing any study procedure.
• Patients must be 18 years of age or older.
• Patients must have Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
• A paraffin-embedded tumor sample must be available for the associate molecular study.
• Body weight >30 Kg.
• Adequate normal organ and marrow function.
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients.
• Patient is willing and able to comply with the protocol for the duration of the study.

Exclusion Criteria

• Involvement in the planning and/or conduct of the study (applies to both Sponsor staff and/or staff at the study site).
• Participation in another clinical study with an investigational product during the last 30 days.
• Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Previous treatment with radiotherapy to the bladder, systemic chemotherapy or immune checkpoint inhibitors. Prior intravesical Bacillus Calmette-Guérin (BCG) treatment for non-muscle invasive bladder cancer is allowed, 28 days prior to study.
• Presence of regional lymph node or metastatic extension of the disease.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) >.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.

• Any concurrent chemotherapy, investigational product (IP) other than studied in this protocol, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders.
• Uncontrolled intercurrent illness.
• History of another primary malignancy.
• History of active primary immunodeficiency.
• Active infection.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of the investigational medical products (IMP).
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study.
• Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
• Known allergy or hypersensitivity to IP or any excipient.