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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Solid Tumors, Metastatic Urothelial Carcinoma & Renal Pelvis & Ureter

Intervention / Treatment
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* Drug: PRN1371


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRN1371<br>Drug: PRN1371 | Drug: PRN1371<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment related Grade 3 and/or Grade 4 adverse events, defined as dose limiting toxicities, for the doses of PRN1371 |  | 28 days on average | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of PRN1371 including area under the serum concentration-time curve |  | Days 1 and 15 | 
| Pharmacokinetic profile of PRN1371 including maximum serum concentration |  | Days 1 and 15 | 
| Pharmacokinetic profile of PRN1371 including time to maximum serum concentration |  | Days 1 and 15 | 
| Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on phosphate levels |  | While being treated with PRN1371 (expected average of 16 weeks) | 
| Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on calcium levels |  | While being treated with PRN1371 (expected average of 16 weeks) | 
| Pharmacodynamic profile of PRN1371 including the effect of PRN1371 on serum FGF23 (Part A only) levels |  | While being treated with PRN1371 (expected average of 16 weeks) | 
| Objective response rate (ORR) as measured by RECIST v1.1 in patients treated with PRN1371 |  | Every 8 weeks while being treated with PRN1371 (expected average of 16 weeks) | 
| Duration of response in patients treated with PRN1371 |  | Every 8 weeks while being treated with PRN1371 (expected average 16 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FGFR