Durvalumab + Olaparib for Bladder Cancer

(BAYOU Trial)

Not currently recruiting at 49 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, PARP inhibitors

Disqualifiers: Autoimmune disorders, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

Duration: 31 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two treatments, Durvalumab (an immunotherapy drug) and Olaparib (a PARP inhibitor), for individuals with advanced bladder cancer that cannot be surgically removed. It targets those unable to undergo standard platinum-based chemotherapy. The trial aims to determine if combining these drugs can slow cancer growth or improve symptoms. Individuals with stage IV bladder cancer who have not received prior treatment and cannot undergo platinum chemotherapy may be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any immunosuppressive medication within 14 days before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Durvalumab is generally well-tolerated. In studies, most patients did not experience severe side effects. However, about 7% of patients encountered serious issues such as blood in urine, lung infection, and skin rash, which were considered manageable.

For Olaparib, research indicates it is also well-tolerated, particularly in patients with BRCA1/2 mutations. It has been used safely in other cancers, such as ovarian cancer, and has helped patients live longer without their cancer worsening. These findings suggest that both Durvalumab and Olaparib have manageable safety profiles, though some side effects may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Durvalumab and Olaparib for bladder cancer because they offer a novel approach compared to standard treatments like chemotherapy and immunotherapy alone. Durvalumab is an immunotherapy that works by blocking the PD-L1 protein, helping the immune system to better attack cancer cells. Olaparib, on the other hand, is a PARP inhibitor that interferes with cancer cell DNA repair, potentially enhancing the effectiveness of Durvalumab. This combination aims to boost the immune response while directly targeting cancer cell survival mechanisms, providing a potentially more effective treatment option for bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that using Durvalumab and Olaparib together may help treat bladder cancer. In this trial, one group of participants will receive Durvalumab with a placebo, while another group will receive the combination of Durvalumab and Olaparib. Some studies have indicated that this combination more than doubled the time patients responded to treatment compared to standard chemotherapy for certain cancers. One study found that this treatment prevented cancer progression for 15 months, longer than with a placebo. Specifically for bladder cancer, the NEODURVARIB trial demonstrated that this combination is active in treating the disease. These findings suggest that using Durvalumab and Olaparib together could effectively manage advanced bladder cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan Rosenberg, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Mark Lanasa, MD

Principal Investigator

One MedImmune Way,Gaithersburg,Maryland,United States

Are You a Good Fit for This Trial?

This trial is for adults with advanced bladder cancer that can't be surgically removed and who haven't had systemic therapy. They must not qualify for platinum-based chemotherapy, have a certain performance status, and be able to take oral meds. Pregnant or breastfeeding individuals, those with autoimmune diseases, recent major surgery, uncontrolled illnesses, or prior treatments with similar drugs are excluded.

Inclusion Criteria

I cannot receive platinum-based chemotherapy due to certain conditions.

I am post-menopausal or not currently pregnant.

My bladder cancer is advanced and hasn't been treated with systemic therapy.

Exclusion Criteria

I am not currently on any cancer treatments like chemotherapy or hormone therapy.

I have not received a live vaccine in the last 30 days.

I have or had an autoimmune or inflammatory disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab 1500 mg IV every 4 weeks and either Olaparib or placebo orally twice a day

31 months

IV administration every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

31 months

Tumor assessments every 8 weeks for the first 48 weeks, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Olaparib

Trial Overview The BAYOU study is testing the effectiveness of Durvalumab alone versus its combination with Olaparib against bladder cancer in patients ineligible for platinum chemo. It's a phase II trial where participants are randomly assigned to receive either both drugs or one drug plus a placebo without knowing which they're getting.

How Is the Trial Designed?

Group I: Arm 2: Durvalumab/Olaparib Experimental Treatment 2 Interventions

Durvalumab 1500 mg IV q4w starting on week 1 day 1/Olaparib PO 300 mg BID adjusted based on patient's creatinine clearance.

Group II: Arm 1: Durvalumab/Placebo Experimental Treatment 2 Interventions

Durvalumab 1500 mg intravenous (IV) every 4 weeks (q4w) starting on week 1 day 1/Placebo orally (PO) twice a day (BID) starting on week 1 day 1.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

The combination of durvalumab and cabozantinib was found to be safe in a phase 2 study with 16 patients, showing no severe treatment-related adverse events in the first two cycles, although common mild side effects included fatigue and diarrhea.

Preliminary results indicated that 37.5% of patients experienced objective responses, including two complete responses, suggesting that this combination therapy may be effective for patients with advanced metastatic urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib Plus Durvalumab in Patients With Advanced Urothelial Carcinoma After Platinum Chemotherapy: Safety and Preliminary Activity of the Open-Label, Single-Arm, Phase 2 ARCADIA Trial. Marandino, L., Raggi, D., Calareso, G., et al.[2021]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

In a study involving 34 patients with BRCA1 or BRCA2 mutated metastatic breast cancer, the combination of olaparib and durvalumab demonstrated promising antitumor activity, with 80% of patients showing disease control at 12 weeks.

The treatment was generally safe, with 32% of patients experiencing grade 3 or worse adverse events, but no treatment-related deaths were reported, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Domchek, SM., Postel-Vinay, S., Im, SA., et al.[2021]

In a phase I study involving 26 women with recurrent cancers, the combination of the PD-L1 inhibitor durvalumab with olaparib or cediranib was found to be tolerable and showed promising anti-tumor activity, with an 83% disease control rate for the durvalumab plus olaparib group.

The recommended phase II doses were established as durvalumab 1,500 mg every 4 weeks with olaparib 300 mg twice daily, or cediranib 20 mg on an intermittent schedule, indicating that these combinations could be viable options for further investigation in treating recurrent women's cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escalation, Phase I Study. Lee, JM., Cimino-Mathews, A., Peer, CJ., et al.[2022]

In a phase II study involving 61 patients with muscle-invasive urothelial carcinoma, the addition of neoadjuvant durvalumab to standard chemotherapy resulted in a high event-free survival (EFS) rate of 76% at 2 years, indicating promising efficacy in this treatment approach.

The study also reported an overall survival (OS) rate of 85% at 2 years, although 42% of patients experienced grade 3 or 4 treatment-related adverse events during the neoadjuvant phase, highlighting the need to balance efficacy with safety in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17. Cathomas, R., Rothschild, SI., Hayoz, S., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Neoadjuvant immunotherapy using immune checkpoint inhibitors (ICIs) like anti-PD-(L)1 and anti-CTLA-4 antibodies shows promising efficacy in localized muscle-invasive bladder cancer, with pathological complete response rates between 31% and 46%.

The safety profile of these treatments is generally acceptable, with severe adverse events reported in 6% to 41% of patients, indicating that while there are risks, the potential benefits warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer. Peyrottes, A., Ouzaid, I., Califano, G., et al.[2021]

Citations

1. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/imfinzi-regimen-reduced-risk-of-disease-recurrence-death-32-percent-high-risk-non-muscle-invasive-bladder-cancer-in-the-potomac-phase-iii-trial.html

Imfinzi regimen reduced the risk of disease recurrence or ... The results of POTOMAC showed that adding one year of durvalumab to BCG bladder instillation treatment reduced the risk of recurrence by 32 per ...

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/lynparza-olaparib-and-imfinzi-durvalumab-demonstrated-strong-clinical-benefit-and-more-than-doubled-median-duration-of-response-vs-chemotherapy-in-patients-with-mismatch-repair-proficient-advanced-or-recurrent-endometrial-cancer.html

LYNPARZA® (olaparib) and IMFINZI® (durvalumab) ... LYNPARZA (olaparib) and IMFINZI (durvalumab) demonstrated strong clinical benefit and more than doubled median duration of response vs. chemotherapy.

3. myastrazeneca.co.uk myastrazeneca.co.uk/imfinzi/endometrial-cancer/clinical-trial.html

DUO-E (Imfinzi (durvalumab) & Lynparza (olaparib)) The Imfinzi + Lynparza regimen offers a PFS of 15 months (vs 9.7 months in placebo arm) for advanced and recurrent pMMR endometrial cancer (P-value not tested).

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40298406/

The NEODURVARIB Trial Conclusions: The combination of neoadjuvant durvalumab and olaparib shows therapeutic activity in bladder cancer. Resistance mechanisms seem ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04538378

Study Details | NCT04538378 | Olaparib (LYNPARZA) Plus ... This is an open label Phase II study evaluating the combination of durvalumab and olaparib in participants with EGFR-mutated non-small-cell lung carcinoma.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27269937/

Safety and Efficacy of Durvalumab (MEDI4736), an ... - PubMed Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.67.9761

Safety and Efficacy of Durvalumab (MEDI4736), an Anti– ... Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with UBC, many of whom were heavily ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04349-7/fulltext

273MO DURANCE: A phase Ib/II study to assess the safety ... Three serious AEs (haematuria, lung infection, and maculopapular rash) were observed in 1/14 patients (7.1%) during DLT period, all of which were considered ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.778

Feasibility and safety results from RAD-IO Recent phase 3 results with peri-operative durvalumab show a 25% reduction in the risk of death compared to standard of care. Methods: RADIO is ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT03528694

Study Details | NCT03528694 | Assessment of Efficacy and ... Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer (POTOMAC).