The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.
This open-label (all people know identity of intervention) and multicenter (when more than one hospital or medical school team work on a medical research study) study to establish the recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have received any number of lines of prior therapy, and participants enrolled in Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination to further characterize safety and clinical activity. The study will be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and safety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
125
Participants will receive erdafitinib orally.
Participants will receive cetrelimab by intravenous infusion.
Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy.
Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy.
Rocky Mountain Cancer Centers
Aurora, Colorado, United States
Norton Cancer Institute
Louisville, Kentucky, United States
Maryland Oncology Hematology, PA
Rockville, Maryland, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Weill Cornell Medical College - NY Presbyterian Hospital
New York, New York, United States
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs)
Number of participants with DLTs were reported. The DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE version 5.0) are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) non-hematological toxicity or hematological toxicity.
Time frame: Up to 8 weeks
Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment
ORR is defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version1.1. As per RECIST version 1.1, CR: disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR: greater than or equal to (\>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.
Time frame: From Day 1 up to 36 months
Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
Number of participants with TEAEs were reported. An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as adverse events with onset or worsening on or after date of first dose of study treatment.
Time frame: From Day 1 up to 36 months
Phase 1b and Phase 2: Plasma Concentration of Erdafitinib
Time frame: Up to 6 years 1 month
Phase 1b and Phase 2: Serum Concentration of Cetrelimab
Time frame: Up to 6 years 1 month
Phase 1b: Plasma Concentration of Platinum (Cisplatin and Carboplatin) Chemotherapy
Time frame: Up to 6 years 1 month
Phase 1b and Phase 2: Number of Participants With Anti-Cetrelimab Antibodies
Time frame: Up to 6 years 1 month
Phase 2: Number of Participants With Serious Adverse Events (SAEs)
Time frame: Up to 6 years 1 month
Phase 2: Number of Participants With Abnormal Laboratory Values
Time frame: Up to 6 years 1 month
Phase 2: Duration of Response (DoR)
Time frame: Up to 6 years 1 month
Phase 2: Time to Response (TTR)
Time frame: Up to 6 years 1 month
Phase 2: Progression-free Survival (PFS)
Time frame: Up to 6 years 1 month
Phase 2: Overall Survival (OS)
Time frame: Up to 6 years 1 month
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White Plains Hospital Center for Cancer Care
White Plains, New York, United States
Levine Cancer Institute, Carolinas HealthCare System
Charlotte, North Carolina, United States
Toledo Clinic Cancer Centers
Toledo, Ohio, United States
Penn State Hershey Cancer Institute
Hershey, Pennsylvania, United States
Texas Oncology, P.A.
Fort Worth, Texas, United States
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