Hematologic Malignancies, Solid Tumor
Conditions
Keywords
Solid tumor malignancy, hematologic malignancy, mutation, translocations, amplifications,, fusions, signature, FGFR, ligand, BGJ398
Brief summary
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.
Interventions
DRUGBGJ398
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | 16 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | every 8 weeks until death, assessed up to 24 months | 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 |
| Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Months 1, 2, 3, 4, 5, 6, 12, 18, 24 | — |
| Overall Response (OR) or Partial Response (PR) or Greater | baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months | 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 |
| Kaplan-Meier Estimates of Survival Rate, % (95% CI) | months 3, 6, 9, 12, 24 | 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. |
| Number of Participants With 99 Day Minimum Duration of Response (DOR) | baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months | 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 |
| Overall Survival (OS) | every 8 weeks until death, assessed up to 36 months | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BGJ398 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. | 84 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Death | 2 |
| Overall Study | disease progression | 57 |
| Overall Study | non-compliance with study | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | study terminated by by sponsor | 1 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | BGJ398 |
|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 12.08 |
| Age, Customized >=65-<75 years | 21 Participants |
| Age, Customized <65 years | 54 Participants |
| Age, Customized >=75 years | 9 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black | 6 Participants |
| Race/Ethnicity, Customized Caucasian | 74 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 83 |
| other Total, other adverse events | 81 / 83 |
| serious Total, serious adverse events | 33 / 83 |
Outcome results
Primary
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
Time frame: 16 weeks
Population: Full Analysis Set (FAS): The FAS included all enrolled patients who received at least 1 dose of study drug. The FAS was the primary set for efficacy analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGJ398 | Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Complete response (CR) | 0 Participants |
| BGJ398 | Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Partial response (PR) | 6 Participants |
| BGJ398 | Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Progressive disease (PD) | 54 Participants |
| BGJ398 | Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Stable disease (SD) | 7 Participants |
| BGJ398 | Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Non-evaluable (NE) | 13 Participants |
| BGJ398 | Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Overall response rate (ORR: CR + PR) | 6 Participants |
| BGJ398 | Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment | Clinical benefit rate (CBR: CR+PR+SD) | 12 Participants |
Secondary
Kaplan-Meier Estimates of PFS Rate, % (95% CI)
Time frame: Months 1, 2, 3, 4, 5, 6, 12, 18, 24
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 24 | 0.0 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 1 | 88.0 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 2 | 38.0 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 3 | 32.3 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 4 | 20.0 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 5 | 15.4 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 6 | 12.3 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 12 | 10.2 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of PFS Rate, % (95% CI) | Month 18 | 6.1 percent of participants |
Secondary
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.
Time frame: months 3, 6, 9, 12, 24
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BGJ398 | Kaplan-Meier Estimates of Survival Rate, % (95% CI) | Month 24 | 19.5 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of Survival Rate, % (95% CI) | Month 3 | 75.9 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of Survival Rate, % (95% CI) | Month 6 | 50.1 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of Survival Rate, % (95% CI) | Month 9 | 39.4 percent of participants |
| BGJ398 | Kaplan-Meier Estimates of Survival Rate, % (95% CI) | Month 12 | 35.1 percent of participants |
Secondary
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
Time frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGJ398 | Number of Participants With 99 Day Minimum Duration of Response (DOR) | 6 Participants |
Secondary
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
Time frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BGJ398 | Overall Response (OR) or Partial Response (PR) or Greater | 6 participants |
Secondary
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
Time frame: every 8 weeks until death, assessed up to 36 months
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGJ398 | Overall Survival (OS) | 6.2 months |
Secondary
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
Time frame: every 8 weeks until death, assessed up to 24 months
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BGJ398 | Progression-Free Survival (PFS) | 1.8 months |