BGJ398 for Patients With Tumors With FGFR Genetic Alterations

Study Overview
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Brief Summary
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The purpose of this signal seeking study was to determine whether treatment with BGJ398 demonstrates sufficient efficacy in select FGFR pathway-regulated solid tumors and/or hematologic malignancies to warrant further study.

Official Title
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Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 6 - BGJ398 for Patients With Tumors With FGFR Genetic Alterations

Conditions
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Solid Tumor, Hematologic Malignancies

Intervention / Treatment
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* Drug: BGJ398


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has a confirmed diagnosis of a select solid tumor (except with a primary diagnosis of Urothelial cell carcinoma, Cholangiocarcinoma, Endometrial cancer, and Glioblastoma multiforme) or hematologic malignancies and is in need of treatment because of progression or relapse. Patient's tumor has been evaluated and pre-identified as having a tumor with a FGFR genetic alteration. The qualifying alteration must be assessed and reported by a CLIA-certified laboratory. Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission. Patient must have progressive and measurable disease per RECIST 1.1. or other appropriate hematological response criteria. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Exclusion Criteria: Patient has received prior treatment with BGJ398 Patients with Central Nervous System (CNS) metastasis or leptomeningeal carcinomatosis Patient has received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug. Patients with acute or chronic pancreatitis Patients with impaired cardiac function or clinically significant cardiac diseases History and/or current evidence of extensive tissue calcification Use of medications that increase serum levels of phosphorus and/or calcium Current evidence of corneal or retinal disorder/keratopathy History and/or current evidence of renal or endocrine alterations of calcium/phosphate homeostasis Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix

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: BGJ398<br>BGJ398 was dosed on a flat scale of 125 mg (e.g., 1 x 100 mg and 1 x 25 mg capsules) once daily for the first 21 days of the 28-day cycle (3 weeks on, 1 week off in a cycle). A complete treatment cycle is defined as 28 days. | Drug: BGJ398<br>* BGJ398 was dosed on a flat scale of 125 mg (e.g., 1 x 100 mg and 1 x 25 mg capsules) once daily for the first 21 days of the 28-day cycle (3 weeks on, 1 week off in a cycle). A complete treatment cycle is defined as 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Tumor Response: Overall response rate (ORR) and clinical benefit rate (CBR) for solid tumor (non-lymphoma) which excludes 3 TIO and 1 Lymphoma patients (hence 80 patients and not 84) Clinical benefit rate for patients with solid tumors were assessed using RECIST 1.1 and include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria may apply Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response (OR) or Partial Response (PR) or Greater | The key secondary endpoint, OR, was determined by Investigator assessment for each tumor assessment and defined as responses of CR and PR per RECIST version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months | 
| Progression-Free Survival (PFS) | Kaplan-Meier estimates of PFS timing, months Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause | every 8 weeks until death, assessed up to 24 months | 
| Kaplan-Meier Estimates of PFS Rate, % (95% CI) |  | Months 1, 2, 3, 4, 5, 6, 12, 18, 24 | 
| Overall Survival (OS) | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause | every 8 weeks until death, assessed up to 36 months | 
| Kaplan-Meier Estimates of Survival Rate, % (95% CI) | Overall survival (OS) is the time from the date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact. | months 3, 6, 9, 12, 24 | 
| Number of Participants With 99 Day Minimum Duration of Response (DOR) | The duration of response (PR or greater) applies only to patients whose best response was PR or greater. It is defined as the Ttime from the first documented response to the date first documented disease progression or relapse or death due to any cause | baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumor malignancy, hematologic malignancy, mutation, translocations, amplifications,, fusions, signature, FGFR, ligand, BGJ398