A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer

A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer

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.

Inclusion Criteria:

• Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
• Metastatic or locally advanced urothelial cancer
• Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
• Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2

Exclusion Criteria:

• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks
• Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation
• Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed
• Active malignancies requiring concurrent therapy other than urothelial cancer
• Symptomatic central nervous system metastases