NCT05241340

Neoadjuvant Sasanlimab With Radiation as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer

A Phase II Clinical Trial of Neoadjuvant Sasanlimab and Stereotactic Body Radiation Therapy as an in Situ Vaccine for Cisplatin-ineligible Muscle Invasive Bladder Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: The Methodist Hospital Research Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, single-institution, single-arm, phase II clinical trial that tests a novel strategy of neoadjuvant Sasanlimab, an immune checkpoint inhibitor (ICI), in combination with stereotactic body radiation therapy as an in-situ vaccination in patients, who are ineligible to receive cisplatin-based chemotherapy and undergoing radical cystectomy for muscle-invasive bladder cancer.

Detailed description

Patients with cT2-T4a, N0, M0 urothelial bladder carcinoma (UBC) after transurethral resection of the bladder will receive 2 doses of sasanlimab (PF-06801591) at the dose of 300mg subcutaneously, followed by 3 doses of radiation (8Gy x 3) prior to surgery (radical cystectomy). Cystectomy will be planned to be done within 6 weeks of the last dose of sasanlimab. Pathologic complete response (pT0) is the primary endpoint, in addition to a safety lead-in endpoint consisting of a composite outcome of feasibility and safety. Exploratory biomarker analysis on tissue/blood samples will include genomic and immune-system profiling in tumor and blood before and after sasanlimab/radiation therapy, and after radical cystectomy.

Conditions

• Urothelial Carcinoma Bladder

Interventions

Type	Name	Description
DRUG	Sasanlimab	Sasanlimab (PF-06801591) is a recombinant humanized monoclonal antibody (immunoglobulin gamma-4 with kappa light chains, IgG4 kappa) directed against programmed death 1 (PD-1). Manufactured by Pfizer, Inc.
RADIATION	Stereotactic Body Radiation Therapy	This current study is designed to deliver a biologically equivalent dose of 43.2Gy using a strategy of HD hypo-fractionated radiation therapy 8Gy x 3 in combination with Sasanlimab
PROCEDURE	Radical Cystectomy + pelvic lymph node dissection + urinary diversion	This will include a cysto-prostatectomy in males or a radical cystectomy with anterior exenteration in females, bilateral pelvic lymph node dissection, and creation of a urinary diversion (ileal conduit, Indiana pouch or orthotopic neo-bladder). Robotic assisted or open surgery will be permitted. Because there is currently equipoise regarding standard or extended template pelvic lymph node dissection, the limits of node dissection will not be protocol mandated. In the standard template, nodal packets will include the common iliac, external iliac, internal iliac (or hypogastric) and obturator nodes. Patients receiving an extended template will have the standard nodes with the addition of the para-aortic, para-caval, pre-sacral, and pre-sciatic node packets. The decision for urinary diversion is multifactorial involving patient factors (e.g., adequate renal function) and preference; thus, it will be made on a case-by-case basis.

Timeline

• Start date: 2022-02-15
• Primary completion: 2025-08-01
• Completion: 2027-04-01
• First posted: 2022-02-15
• Last updated: 2025-10-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study