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

NCT ID: NCT05241340

Last Updated: 2025-10-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-15
• Study Completion Date: 2027-04-01

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open arm

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

Group Type: EXPERIMENTAL

Sasanlimab

Intervention Type: 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.

Stereotactic Body Radiation Therapy

Intervention Type: 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

Radical Cystectomy + pelvic lymph node dissection + urinary diversion

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: RADIATION

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.

Intervention Type: PROCEDURE

Other Intervention Names

PF-06801591; PD-1 Inhibitor

Eligibility Criteria

Inclusion Criteria

1. Capable of giving signed informed consent

2. Age ≥ 18 years

3. ECOG Eastern Cooperative Oncology Group performance status 0-2

4. Predominant (>50%) urothelial carcinoma histology

5. Muscle-invasive bladder cancer (cT2-4a, cN0, cM0)

6. 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

7. 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)

8. 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.

9. 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

10. Able to give informed consent and patient is willing and able to comply with scheduled study visits and treatment plan

11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

12. Meeting the following criteria for sex specific considerations:

<!-- -->

1. Males - for the duration of study and for at least 6 months after the last dose of study drug (Sasanlimab):

1. Refrain from donating sperm and be abstinent from intercourse OR Agree to use male condom and also consider the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant

2. Females:

a) Eligible to participate if not pregnant or breast feeding AND Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and is using a contraceptive method that is highly effective (failure rate of < 1% per year), with low user dependency during the during the study treatment and for at least 6 months after the last dose of study drug (Sasanlimab) b) A WOCBP must have a negative, highly sensitive (at least 25 IU/mL) pregnancy test by urine or serum testing within 24 hours before the first dose of study drug (Sasanlimab). In cases where the urine test cannot be confirmed to be negative, a serum pregnancy test will be used.

Exclusion Criteria

1. Lymphadenopathy (>1cm short-axis measurement on CT/MRI Imaging or biopsy proven)

2. Metastatic disease

3. Prior systemic chemotherapy for bladder cancer (however, may have had intra-vesical chemotherapy such as gemcitabine, docetaxel or mitomycin-C)

4. Prior treatment with systemic anti-cancer investigational agent

5. 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

6. Previous radiation therapy to the bladder

7. Active or history of autoimmune disease which may deteriorate when receiving immune checkpoint blockade.

1. 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

2. Participants with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

8. Severe active infections (e.g., pulmonary tuberculosis) requiring systemic therapeutic oral or IV antibiotics within 2 weeks prior to study entry.

9. Clinically significant, multiple or severe drug allergies, intolerance to topical corticosteroids

10. 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.

11. Active, uncontrolled HIV/AIDS infection (well-controlled HIV patients may be allowed).

12. 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.

13. Prior treatment with immune-stimulatory agents including interleukin (IL)-2, IL-15, interferon (INF)- γ.

14. Vaccination within 4 weeks from study screening and while on study treatment unless administration of inactivated vaccines.

15. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

16. Clinically significant (active) cardiovascular disease including the following: cerebral vascular accident/stroke <6 months prior to screening; myocardial infarction <6 months prior to screening; unstable angina; congestive heart failure (≥New York Heart Association Classification Class III); or serious cardiac arrhythmia (uncontrolled, clinically significant) requiring medication.

17. Q-T interval corrected for heart rate (QTc) >450 msec for male participants or QTc >470 msec for female participants or QTc >480 msec in participants with right bundle branch block

18. Prior organ transplantation or allogenic stem cell transplantation.

19. Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis.

20. Patients with intolerance to or who have had a severe (Grade ≥3) allergic or anaphylactic reaction to antibodies or infused therapeutic proteins

21. Pregnant female patients; breastfeeding female patients; male patients able to father children and female patients of childbearing potential who are unwilling or unable to use a highly effective method(s) of contraception as outlined in this protocol for at least 6 months after the last dose of Sasanlimab (PF-06801591)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Raj Satkunasivam

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raj Satkunasivam, MD

Role: PRINCIPAL_INVESTIGATOR

Houston Methodist Hospital, Houston Methodist Research Institute

Locations

Houston Methodist Hospital

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35703113 (View on PubMed)

Other Identifiers

PRO00032433

Identifier Type: -

Identifier Source: org_study_id