A Study of Durvalumab Alone and Durvalumab+Olaparib in Advanced, Platinum-Ineligible Bladder Cancer (BAYOU)

A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer

This is a Phase II, randomized, double-blind, placebo controlled, multi-center, comparative global study to determine the efficacy and safety of durvalumab + olaparib combination therapy versus durvalumab + placebo (durvalumab monotherapy) as first-line treatment in patients ineligible for platinum-based chemotherapy with unresectable Stage IV urothelial cancer (UC).

Eligibility Criteria:
Inclusion criteria:

1. Provision of signed and dated, written ICF
2. Histologically or cytologically documented TCC/UC of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) also meeting the following: Unresectable, Stage IV disease; No prior systemic therapy for unresectable, Stage IV disease.
3. Ineligible for platinum-based chemotherapy defined as (i) in the opinion of the Investigator, unfit for carboplatin-based chemotherapy and (ii) meeting one of the following criteria: CrCl \<60 mL/min calculated by Cockcroft-Gault equation; Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss (25 dB in 2 consecutive wave ranges); CTCAE Grade ≥2 peripheral neuropathy; New York Heart Association Class III heart failure; ECOG 2.
4. Known tumor HRR mutation status prior to randomization.
5. World Health Organization (WHO)/ECOG performance status of 0, 1, or 2.
6. Patients with at least 1 RECIST 1.1 target lesion at baseline.
7. Ability to swallow oral medications.
8. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Exclusion criteria

1. Active or prior documented autoimmune or inflammatory disorders.
2. Other invasive malignancy within 5 years before the first dose of the IP.
3. Major surgical procedure within 28 days prior to the first dose
4. Brain metastases or spinal cord compression unless the patient's condition is stable and off steroid for at least 14 days
5. History of active primary immunodeficiency.
6. Active infection including tuberculosis (TB)
7. History of allogenic organ transplantation.
8. Uncontrolled intercurrent illness
9. Prior exposure to a PARP inhibitor or immune-mediated therapy.
10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
11. Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP.
12. No radiation therapy is allowed, unless it is (1) definitive radiation that had been administered at least 12 months prior; (2) palliative radiation to the brain, with associated criteria for stability or lack of symptoms; or (3) palliative radiation to painful bony lesions (this must comprise less than 30% of the bone marrow) or symptomatic pelvic soft tissue mass(es).
13. Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP.
14. Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products.
15. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and 6 months for participants taking also Olaparib in case of female participants, 90 days after receipt of the last dose of the IP in case of male participants.