A study, testing the safety and effectiveness of an experimental drug known as B-701, that binds to a protein receptor called FGFR3, and another type of anti-cancer drug known as Pembrolizumab in Subjects with bladder cancer that recurred or got worse following treatment with standard therapy.
- Conditions
- ocally advanced or Metastatic Urothelial CarcinomaMedDRA version: 20.0 Level: PT Classification code 10005005 Term: Bladder cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001292-23-NL
- Lead Sponsor
- Rainier Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 74
1. Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
For subjects in the Phase 2 MF cohort, tumors must have at least one of the following FGFR3 mutations: R248C, S249C, G370/2C, S371/3C, Y373/5C, G380/82R, F384/6L, K650/2X (X=E,T or M) or FGFR3- TACC3 fusion, as shown by tests performed by a CAP or CLIA certified laboratory (or equivalent outside of the US) on samples that were obtained at or after the time when the subject was found to have muscle invasive / metastatic disease or high grade papillary non-muscle invasive disease.
In the absence of pre-existing genetic test results, subjects can submit archival tissue (obtained at or after the time subject was found to have muscle invasive / metastatic disease) for genetic testing. If no suitable tissue is available, a blood sample may be used to determine FGFR3 genetic status. Subsequent to subject enrollment, blood samples used to determine FGFR3 status, or previous test results that were not provided by Foundation Medicine will be verified using archival tissue or the first biomarker tumor biopsy sample.
2. Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy OR Have a PD-L1 positive tumor (per label) at the time of metastatic disease, and are not eligible for cisplatin-containing chemotherapy defined as meeting any one of the criteria as specified in the protocol
3.Have available archival tumor or be willing to undergo diagnostic biopsy at screening. Sample must be of suitable quality and quantity to satisfy group assignment and biomarker endpoints (as described in the Sample Collection & Processing Manual).
4. Have measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
5. Male and female subjects, age = 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1 (see Appendix 1).
7. Willingness to avoid pregnancy or fathering children based on the criteria as described in study protocol.
8.Ability to understand and sign informed consent form:
(ICF) and comply with all study procedures
9. Have adequate hematologic and end organ function defined by the following laboratory results obtained within 2 weeks prior to the first dose of study treatment:
a) Absolute neutrophil count = 1,500/µL.
b) Platelet count = 100,000/µL.
c) Hemoglobin = 9.0 g/dL without transfusion.
d) Albumin = 2.5 g/dL.
e) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) = 2.5 × upper limit of normal (ULN), with the following exceptions:
- Subjects with documented bone metastases: ALP = 5 × ULN.
- Creatinine clearance = 30 mL/min on the basis of the Cockroft Gault glomerular filtration rate estimation: ((140-age)×(weight in kg)×(0.85 if female) )/(72×(serum creatinine in mg/dL))
f) Prothrombin time/international normalized
1. Participants with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on the Screening chest CT scan.
2. Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor or FGFR inhibitor.
3. Patients with autoimmune disease or medical conditions that required systemic corticosteroids (> 10 mg/day prednisone or its equivalent) or other immunosuppressive medications or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment. Note Replacement therapy (e.g. physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
4. Prior anti-cancer therapy (e.g. biologic or other targeted therapy, chemotherapy or hormonal therapy) within 14 days prior to the first dose of study medication.
A washout of less than 14 days may be allowed after discussion with the Medical Monitor, provided that the subject has recovered from any clinically relevant toxicity (Exception: participants with neuropathy of Grade 1 will be allowed study entry).
5. Acute clinical AEs, except for alopecia, from any previous treatments must have resolved to = Grade 1 or chronic defined as present for more than 6 months without worsening and not greater than Grade 2.
6. Laboratory AEs from any previous treatments must have resolved to = Grade 1 or to within 10% of baseline prior to the first dose of study treatment.
7. Participants who are receiving or have received any other investigational drugs or devices within in the 2 weeks prior to the first dose of study medications.
8. Participants with a diagnosis of immunodeficiency.
9. Primary central nervous system (CNS) malignancy or CNS metastases.
10. Participants with a history of allergic reactions attributed to monoclonal antibody therapy (or recombinant antibody-related fusion proteins).
11. History of major bleeding (requiring a blood transfusion = 2 units) not related to a tumor within the past 12 months.
12. History of clinically significant coagulation or platelet disorder in the past 12 months.
13. Participants who have not recovered adequately from the toxicity and/or complications from the interventions prior to starting therapy.
14. Incomplete healing from wounds from prior surgery (wounds larger than 2 cm in length) within 28 days prior to first dose of study treatment.
15. Participants with an active uncontrolled infection requiring systemic therapy (e.g., IV antibiotics or antifungal therapy).
Note: The use of oral anti-infectious agents for prophylaxis or treatment of resolving infections is not considered exclusionary under this rule.
16. Participants who have received a live vaccine within 30 days of planned start of study therapy.
Note: Seasonal influenza vaccines with inactivated flu vaccines are allowed; however, live attenuated vaccines such as intranasal influenza vaccines (e.g., Flu Mist®) are not allowed.
17. Participants with uncontrolled intercurrent illn
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method