Phase II Study of Sasanlimab and Sacituzumab Govitecan in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer Patients
- Trial ID
- 2024-518486-10-00
- Protocol
- APRO07-2022
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of the combination of sasanlimab and sacituzumab govitecan in patients with Bacillus Calmette-Guérin (BCG)-unresponsive **Non-Muscle Invasive Bladder Cancer (NMIBC)**. This will be assessed by the complete response (CR) rate of high-risk disease at 3 months. The clinical relevance of this objective lies in its potential to provide an effective treatment option for patients who do not respond to BCG therapy, which is a common first-line treatment for NMIBC.
Secondary objectives include:
- To further assess the safety and tolerability of the sasanlimab plus sacituzumab govitecan combination in patients with BCG-unresponsive NMIBC.
- To evaluate the efficacy of the combination in terms of complete response rate of high-risk disease at 6, 12, 18, and 24 months.
- To assess the duration of complete response (DOR) for high-risk disease and any disease as a sign of preliminary efficacy of the combination therapy.
- To evaluate progression-free survival (PFS) to worsening of grade or stage or death for the combination in patients with BCG-unresponsive NMIBC.
- To assess the efficacy of the combination in terms of 6-month, 12-month, 18-month, and 24-month rates of overall survival (OS) and PFS to worsening of grade or stage (progression to muscle-invasive or metastatic) or death.
Participants
The clinical trial involves participants diagnosed with **Non-Muscle Invasive Bladder Cancer**. The study population includes both male and female subjects, aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants are required to have adequate organ function and no other malignancy diagnosed within the last two years, except for adequately treated non-melanoma skin cancer and carcinoma in situ of the cervix. The trial population was selected based on a histologically confirmed diagnosis of BCG-unresponsive high-risk, non-muscle invasive urothelial carcinoma, and participants must have refused or be ineligible for radical cystectomy. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include the willingness to avoid pregnancy or fathering children during and after the study period. The trial includes a vulnerable population, and both genders are represented in the study cohort.
Plans and Procedures
The clinical trial is a **phase II** prospective, open-label, multi-centre, single-arm study designed to evaluate the efficacy of a combination therapy involving **sasanlimab** and **sacituzumab govitecan** in patients with **BCG-unresponsive non-muscle invasive bladder cancer**. The primary objective is to assess the complete response rate of high-risk disease at 3 months. The trial is expected to run from March 2023 to March 2025, with an estimated duration of 24 months. Participants will be involved in the study for a maximum treatment period of 104 weeks, depending on their response to the treatment.
The trial design includes an initial screening visit to confirm eligibility based on specific inclusion criteria, such as a histologically confirmed diagnosis of BCG-unresponsive high-risk non-muscle invasive urothelial carcinoma and adequate organ function. Following the screening, participants will undergo a series of study visits, including baseline assessments and regular follow-up visits to monitor treatment efficacy and safety. The follow-up visits will occur at 3, 6, 12, 18, and 24 months, with assessments including cystoscopy, urine cytology, and biopsy when applicable. The end-of-study visit will mark the conclusion of the participant's involvement, where final evaluations will be conducted to assess the overall treatment outcomes.
Participants may be withdrawn from the study early if they experience disease progression, unacceptable adverse events, or if they choose to withdraw consent. The study will also monitor secondary endpoints, such as adverse events, progression-free survival, and overall survival rates at various intervals. The trial is not categorized as low intervention and is conducted under rigorous scientific and ethical standards to ensure the safety and well-being of all participants.
Treatment
The clinical trial involves the administration of **sasanlimab**, a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody. Sasanlimab is provided in the form of a **solution for injection** and is administered subcutaneously. The maximum daily dose is 300 mg, with a total dose not exceeding 300 mg. The treatment period for sasanlimab is up to 104 weeks. This investigational product is developed by Pfizer Inc. and is identified by the sponsor product code PF-06801591. Participant compliance with the dosing schedule is monitored throughout the study.
Another investigational product used in the trial is **sacituzumab govitecan**, marketed under the name Trodelvy. This compound is a **powder for concentrate for solution for infusion** and is administered intravenously. The maximum daily dose is 10 mg, with a total dose not exceeding 10 mg. The treatment period for sacituzumab govitecan is up to 20 weeks. This product is developed by Gilead Sciences Ireland Unlimited Company. The administration and dosing schedules are carefully monitored to ensure participant compliance.
Both investigational products are utilized in a combination therapy to evaluate their efficacy in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). The trial is designed to assess the complete response rate of high-risk disease at 3 months. No non-experimental treatments, such as standard-of-care therapy or placebo, are used in this study. The trial is conducted in a controlled environment to ensure the accuracy and reliability of the results.
Efficacy
The efficacy of the combination treatment of **sasanlimab** and sacituzumab govitecan in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) will be assessed primarily through the Complete Response (CR) rate of high-risk disease at 3 months. This primary endpoint is defined as the absence of high-risk disease or progressive disease, evaluated by cystoscopy, urine cytology, and biopsy when applicable.
Secondary endpoints include the CR rate of high-risk disease at 6, 12, 18, and 24 months, median duration of complete response (DOR) in patients with a CR, progression-free survival (PFS) to worsening of grade, stage (muscle-invasive or metastatic disease), or death, and overall survival (OS). Additionally, 6-month, 12-month, 18-month, and 24-month OS and PFS will be measured. Adverse events (AEs) will also be monitored as part of the secondary endpoints.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent stating that he/she understands the purpose of the study and the procedures involved and agrees to participate in the study.
- Histological confirmed diagnosis of BCG-unresponsive high-risk, nonmuscle invasive urothelial carcinoma obtained via Transurethral resection of bladder tumour (TURBT) no later than 16 weeks prior to screening visit, defined as: a. Persistent or recurrent CIS alone or with recurrent high-grade Ta/T1 (non-invasive papillary disease/tumour invades the subepithelial connective tissue) disease within 16 months of completion of adequate BCG therapy. b. Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy. c. T1 high-grade disease at the first evaluation following an induction BCG. Patients should be allowed to enrol in the study even if more time has elapsed and/or if patient has tried another agent meantime since BCG unresponsiveness was established (on the basis that these situations do not change biology of the disease that initially classified the patient as BCG unresponsive).
- Have refused or are ineligible for radical cystectomy
- Pure or predominant (≥50%) urothelial carcinoma (UC) histology as determined at the local site.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate organ function prior to Cycle 1 Day 1, as specified below: a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without granulocyte colony stimulating factor (GCSF) support); platelet count ≥ 100 x 109/L; haemoglobin ≥ 9 g/dL without transfusion within 1-week preceding study drug administration; b. International normalized ratio (INR) or Prothrombin time (PT) ≤1.5 x upper limit of normal (ULN); c. Hepatic: total bilirubin ≤ 1.5 x ULN, transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/GOT and alanine aminotransferase/serum glutamic pyruvic transaminaseALT/GPT) ≤ 2.5 x ULN; d. Creatinine clearance ≥30 mL/min based either on Cockcroft-Gault estimate or based on urine collection (24 hour).
- No other malignancy (diagnosis within the last 2 years), except for adequately treated non-melanoma skin cancer (basal or squamous) and carcinoma in situ of cervix.
- Willingness to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 6 months after the last dose of study drugs, unless confirmed to be azoospermic (vasectomized or secondary to medical cause). Males must also refrain from donating sperm for the purposes of assisted reproduction during the same time-period. b. Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 6 months after the last dose of study drugs. Women of nonchildbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy or ≥ 12 months of amenorrhea) are eligible. Females must also refrain from donating egg (ovum) for the purposes of assisted reproduction during the same time period.
- Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion Criteria
- Evidence of muscle-invasive, locally advanced, or metastatic urothelial cancer or concurrent UC in upper urinary tracts (ureters or renal pelvis).
- Involvement of the prostatic urethra or invasive prostatic transitional cell carcinoma including T1 or greater disease.
- Any systemic or intravesical chemotherapy or immunotherapy from the time of most recent positive TURBT (confirming BCG-unresponsive high-risk, non-muscle invasive urothelial carcinoma) to initiation of study intervention. Intravesical chemotherapy treatment given as part of the most recent cystoscopy/TURBT as per local/regional practices, is acceptable. Limited intravesical chemo is acceptable after discussing with the sponsor.
- Prior immunotherapy with anti PD-1, anti PD-L1, anti PD-L2, or anti cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
- Prior treatment with immunostimulatory agents including interleukin (IL)-2, IL-15, interferon (INF).
- Prior radiation therapy to the bladder.
- Has tumour with any percentage of neuroendocrine or small cell component.
- Major surgical procedure within 28 days prior to the first dose or still recovering from prior surgery. Port placement or any type of central venous placement is not considered major. The same as for biopsy procedures.
- Severe infection within 2 weeks of the first use of study drug.
- Uncontrolled adrenal insufficiency
- True positive test results for active hepatitis B or C during screening.
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure (NyHA>class II), unstable angina pectoris cardiac arrhythmia requiring medication except for atrial fibrillation that is rate controlled with medication, myocardial infarction within 6 months of Cycle 1 Day 1, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
- Known allergy or hypersensitivity to study drug formulations.
- Known history of allergy to protein-based therapies or a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anaemia).
- Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
- Has an active autoimmune disease that has required systemic treatment in the past 6 months (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Pregnancy or breastfeeding.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 01 Mar 2023 | 42 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PF-06801591 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 300 | 104 | PRD7781023 |
Sasanlimab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 300 | 104 | PRD11167182 |
Trodelvy 200 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 10 | 20 | PRD9351384 |