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

NCT05241340 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: PRO00032433
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Urothelial Carcinoma Bladder

Keywords

Bladder Cancer; Muscle Invasive Bladder Cancer; Immune Checkpoint Inhibitor; Immunotherapy; Urothelial Carcinoma of the Bladder; Urologic neoplasms; Neoadjuvant therapy; Radiation; Stereotactic Body Radiation Therapy; Urinary Bladder Diseases; Urologic Diseases; Sasanlimab; Antineoplastic agents; Antineoplastic agents, Immunological

Outcome Measures

Primary Outcomes (2)

• Composite outcome for Feasibility and Safety

  Combination of Sasanlimab and SBRT will be deemed both feasible and safe (composite outcome) if, after the treatment of 10 patients, ≥ 7 of 10 patients meet all of the following feasibility criteria: 1. Receive at least 1 dose of 2 of Sasanlimab 2. Receive at least 2 of 3 fractions SBRT 3. Undergo radical cystectomy RC within 4 weeks of completing therapy (after end of cycle 2) and meet all of the safety criteria, defined as not experiencing any following Common Terminology Criteria for Adverse Events (CTCAE) toxicities up to 4 weeks after the completion of radical cystectomy: 1. Hematologic toxicity ≥ Grade 4 2. Non-hematologic toxicity ≥ Grade 3 3. Non-hematologic toxicity ≥ Grade 2 lasting \>1 week (except alopecia, emesis, and laboratory abnormalities)

  From date of registration to date of death due to any cause, assessed up to 4 weeks after radical cystectomy

• Clinical benefit rate defined as pathologic complete response (pT0)

  Proportion of patients experiencing pathologic complete response (pT0) after the study treatment followed by radical cystectomy.

  At time of radical cystectomy

Secondary Outcomes (5)

• Incidence of adverse events graded by NCI CTCAE version 5.0

  From date of registration to date of death due to any cause, assessed up to 12 weeks after radical cystectomy

• Incidence of major surgical complications graded by Clavien-Dindo Scale

  From date of radical cystectomy to date of death, assessed up to 30 days following surgery

• Health Related Quality of Life for Patients with T2-T4 muscle invasive bladder cancer

  From date of registration to date of death due to any cause, assessed up to 24 months after radical cystectomy

• Overall survival (OS)

  From date of registration to date of death due to any cause, assessed up to 24 months after radical cystectomy

• Recurrence free survival (RFS)

  From date of registration to date of death due to any cause, assessed up to 24 months after radical cystectomy

Study Arms (1)

Open arm

EXPERIMENTAL

All patients will receive study interventions (sasanlimab and SBRT) and standard-of-care radical cystectomy.

Drug: Sasanlimab; Radiation: Stereotactic Body Radiation Therapy; Procedure: Radical Cystectomy + pelvic lymph node dissection + urinary diversion

Interventions

Sasanlimab DRUG

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.

Also known as: PF-06801591, PD-1 Inhibitor

Open arm

Stereotactic Body Radiation Therapy RADIATION

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

Open arm

Radical Cystectomy + pelvic lymph node dissection + urinary diversion PROCEDURE

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.

Open arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent
• Age ≥ 18 years
• ECOG Eastern Cooperative Oncology Group performance status 0-2
• Predominant (\>50%) urothelial carcinoma histology
• Muscle-invasive bladder cancer (cT2-4a, cN0, cM0)
• Decline/refuse OR Ineligible to receive cisplatin-based Neoadjuvant Chemotherapy due to at least one of the following criteria:
• a. Creatinine clearance less than 60 mL/min b. Eastern Cooperative Oncology Group performance status of ≥ 2 c. Grade ≥ 2 hearing loss d. Grade ≥ 2 neuropathy
• Adequate Bone Marrow Function (without hematopoietic growth factor support within 14 days prior to study screening), defined as:
• a. Absolute neutrophil count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L b. Platelets ≥100,000/mm3 or 100 x 109/L c. Hemoglobin ≥9 g/dL (≥5.6 mmol/L)
• Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance.
• Adequate liver function, including:
• a. Aspartate and alanine aminotransferase (AST and ALT) ≤ 2.5 × the upper normal limit range (ULN) b. Total serum bilirubin ≤ 1.5 x ULN
• Able to give informed consent and patient is willing and able to comply with scheduled study visits and treatment plan
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
• Meeting the following criteria for sex specific considerations:

You may not qualify if:

• Lymphadenopathy (\>1cm short-axis measurement on CT/MRI Imaging or biopsy proven)
• Metastatic disease
• Prior systemic chemotherapy for bladder cancer (however, may have had intra-vesical chemotherapy such as gemcitabine, docetaxel or mitomycin-C)
• Prior treatment with systemic anti-cancer investigational agent
• Other malignancy within 2 years prior to study screening, or active malignancy except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration) or other concurrent malignancy felt by the investigator has a very low likelihood to become metastatic
• Previous radiation therapy to the bladder
• Active or history of autoimmune disease which may deteriorate when receiving immune checkpoint blockade.
• These autoimmune conditions include but are not limited to limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
• Participants with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Severe active infections (e.g., pulmonary tuberculosis) requiring systemic therapeutic oral or IV antibiotics within 2 weeks prior to study entry.
• Clinically significant, multiple or severe drug allergies, intolerance to topical corticosteroids
• Current unstable liver or biliary disease, defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
• NOTE: Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -e.g., presence of hepatitis B surface antigen \[HBsAg\] or positive hepatitis C antibody test result at screening) is acceptable.
• Active, uncontrolled HIV/AIDS infection (well-controlled HIV patients may be allowed).
• Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4) antibody. Note: prior intra-vesical BCG therapy is acceptable.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• Pfizer: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77006, United States

Location

Related Publications (1)

• Satkunasivam R, Lim K, Teh BS, Guzman J, Zhang J, Farach A, Chen SH, Wallis CJ, Efstathiou E, Esnaola NF, Sonpavde GP. A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible MIBC: the RAD VACCINE MIBC trial. Future Oncol. 2022 Aug;18(25):2771-2781. doi: 10.2217/fon-2022-0380. Epub 2022 Jun 15.

  PMID: 35703113 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases

Interventions

Immune Checkpoint Inhibitors; Radiosurgery; Cystectomy; Urinary Diversion

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Raj Satkunasivam, MD

  Houston Methodist Hospital, Houston Methodist Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 19, 2022
• First Posted: February 15, 2022
• Study Start: February 15, 2022
• Primary Completion: August 1, 2025
• Study Completion (Estimated): April 1, 2027
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)