Durvalumab + Olaparib for Bladder Cancer

(BAYOU Trial)

Recruiting at 36 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

154 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of two drugs, durvalumab and olaparib, for patients with advanced bladder cancer who can't receive standard chemotherapy. Durvalumab helps the immune system attack cancer, while olaparib makes it harder for cancer cells to repair themselves. The goal is to see if this combination is more effective than using durvalumab alone.

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.

What data supports the effectiveness of the drug Durvalumab + Olaparib for bladder cancer?

Research shows that Durvalumab, when used alone or with other drugs, has been effective in treating bladder cancer, especially in patients who have not responded well to previous chemotherapy. Additionally, combining Durvalumab with Olaparib, which targets specific genetic mutations in cancer cells, has shown promise in treating metastatic urothelial carcinoma, a type of bladder cancer. ^{1 2 3 4 5}

What is known about the safety of Durvalumab and Olaparib in humans?

Durvalumab and Olaparib have been studied together in various cancers, including breast and urothelial carcinoma, and have shown to be generally safe with no dose-limiting toxicities reported. Common side effects include fatigue and hypertension (high blood pressure), but these were not severe enough to limit dosing in trials. ^{2 4 6 7 8}

How is the drug combination of Durvalumab and Olaparib unique for bladder cancer?

The combination of Durvalumab, an immune checkpoint inhibitor, and Olaparib, a PARP inhibitor, is unique for bladder cancer because it targets both the immune system and DNA repair mechanisms, potentially enhancing antitumor activity in patients with specific genetic mutations that make tumor cells more sensitive to this approach. ^{1 2 3 5 6}

Research Team

Jonathan Rosenberg, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Mark Lanasa, MD

Principal Investigator

One MedImmune Way,Gaithersburg,Maryland,United States

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU). [2023]

3. United States 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. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer. [2021]

6. England 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. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

8. United States 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. [2022]