A Dose Escalation Study in Solid Tumors and a Dose Expansion Study of PRN1371 in Adult Patients With Metastatic Urothelial Carcinoma

A Phase I Open-Label, Multicenter, Dose-Escalation Study of PRN1371, a FGFR 1-4 Kinase Inhibitor, in Adult Patients With Advanced Solid Tumors, Followed by an Expansion Cohort in Patients With Metastatic Urothelial Carcinoma With FGFR 1, 2, 3, or 4 Genetic Alterations

This is a multi-center, open label, non-randomized Phase 1 study, to be conducted in two parts, Part A, and Part B. Part A in solid tumors included the dose escalation phase for evaluating the safety and tolerability profile of PRN1371, a FGFR 1-4 Kinase inhibitor. Part B is the Cohort Expansion phase in patients with metastatic urothelial carcinoma to further evaluate safety and tolerability, preliminary activity, PK, and PD in patients with FGFR genetic alterations.

The protocol specifies rules for dose-limiting toxicity and a maximum tolerated dose (MTD). To gain further experience with the MTD, and/or at some lower optimal biologic dose level, an expansion cohort (Part B) enrolled patients with metastatic urothelial carcinoma with fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4 genetic alterations.

Inclusion Criteria:

• Age ≥ 18 years
• Histological or cytological documentation of an advanced solid tumor
• Subject must have metastatic or recurrent disease and have failed first-line systemic treatment, and if indicated, failed approved second-line therapy, and for whom no standard therapy options are anticipated to result in a durable remission
• Subject must have evaluable, progressive, and measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, Version 1.1
• Adequate bone marrow, liver, and renal function
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

For Part B (expansion) in subjects metastatic urothelial carcinoma:

• The patient's tumor has been evaluated and prospectively identified as having FGFR 1, 2, 3, or 4 genetic alterations.

Exclusion Criteria:

• Patients who have received adequate prior treatment with a highly selective FGFR inhibitor
• Patients with other major uncontrolled medical conditions, e.g., recent myocardial infarction, stroke, diabetes, active hepatitis
• Patients who have received prior systemic anticancer therapy ≤ 3 weeks prior to study start (6 weeks for nitrosourea, antibodies, or mitomycin-C)
• Patients diagnosed with another primary malignancy within 3 years prior to study start, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma, or other non-melanomatous skin cancer, or carcinoma in situ of the uterine cervix
• Patients with glioblastoma multiforme
• Patient has a primary neoplasm of the brain or known uncontrolled metastases to the central nervous system (CNS).