NCT03498196

A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer

A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer (BL-AIR: Bladder Cancer-Avelumab for Invasive Resectable Disease)

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a pilot study of avelumab in patients with non-metastatic, muscle invasive bladder cancer who are eligible for radical cystectomy (RC), but are ineligible for cisplatin based neoadjuvant therapy. The target recruitment is 10 evaluable patients for this window of opportunity study. Pre- and post-treatment tumor samples from transurethral resection of the bladder tumor and RC will be used for study endpoints.

Detailed description

Avelumab is a fully human monoclonal PD-L1 antibody of the immunoglobulin G1 (IgG1) subclass. It works by binding to PD-L1 on tumor cells, immune cells and/or stromal cells. This prevents PD-L1 from interacting with PD-1. Inhibition of this interaction increases activation/survival of antitumor lymphocytes. It also increases innate immunity by resulting in decreased PD-1 suppression of NK cell function and bolsters antibody production by B cells due to less PD-L1 binding of PD-1 on B-cells. Additionally, avelumab has been suggested to have another mechanism involving antibody dependent cellular cytotoxicity (ADCC). ADCC in these cases involves NK cell recognition and lysis of tumor cells that have antibody bound to PD-L1. By blocking PD-L1, avelumab leads to less CD80 binding by PD-L1 and more CD80-CD28 binding in response to antigen presentation to T-cells. This results in increased costimulatory signaling and is another mechanism by which avelumab may enhance T-cell activation. Avelumab has been shown to be efficacious across multiple metastatic tumor types, including urothelial cancer. The phase Ib study has reported survival and safety outcomes with \>12 months followup using pooled data on 249 patients with metastatic UC (Apolo et al, ESMO Sept 2017). Patients had been treated with a median of 2 prior therapies in the metastatic setting and 13 patients who were cisplatin-ineligible were evaluated for safety alone. PD-L1 expression was not a criterion for enrollment. The confirmed objective response rate (ORR) was 16.1%, with 5% complete responses and 11.2% partial responses. The 6-month progression-free survival was 27%. The ORR was better than or comparable to chemotherapy in historical controls. Among responders, 70.3% were maintained \> 12 months. Treatment-related adverse events (AE) occurred in 70%, with 10.7% of the total with AE's of grade \>3. Immune-mediated AE's occurred in 18.5%, of which 4% were grade \>3. There is currently a phase III clinical trial ongoing comparing avelumab to standard of care chemotherapy in the second line setting or beyond for metastatic UC. Two other checkpoint inhibitors have been approved in the last 2 years for first line treatment of patients with metastatic UC who are ineligible for cisplatin-based therapy.

Conditions

• Bladder Cancer
• Metastatic Bladder Cancer
• Invasive Bladder Cancer

Interventions

Type	Name	Description
DRUG	Avelumab	avelumab 10 mg/kg intravenously every 2 weeks for 3 cycles or 42 days.

Timeline

• Start date: 2018-12-14
• Primary completion: 2019-12-09
• Completion: 2019-12-09
• First posted: 2018-04-13
• Last updated: 2020-08-24
• Results posted: 2020-08-24

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study