PI3K Pathway Activated Tumors
Conditions
Keywords
Solid tumor, malignancy, hematologic malignancy, PI3K pathway activation, P13K activated tumors, BKM120, signature, AML, acute myelogenous leukemia, cervical, ovarian, hepatobiliary, buparlisib
Brief summary
The purpose of this signal seeking study was is to determine whether treatment with BKM120 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.
Interventions
DRUGBKM120
BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28-day cycle
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Patient had a confirmed diagnosis of a solid tumor or hematological malignancy with the exception of endometrial cancer, glioblastoma, nonsmall cell lung cancer, prostate cancer or breast cancer. * Patient's tumor was evaluated and pre-identified to have activation of the PI3K pathway, at 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 was anticipated to result in a durable remission. * Patient must have had progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines * Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Exclusion criteria
Patient had received previous treatment with BKM120 Patient had symptomatic CNS metastases Patient had mood disorder as outlined in Section 5 Patient had received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Clinical Benefit Response Rate | Week 16 | Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at \>=16 weeks. For hematologic tumors other appropriate hematological response criteria was applied. Response criteria: CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm., PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival - Number of Participants With an Event | Every 8 Weeks until death, assessed up to 24 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 |
| Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Timing in Months | baseline up to 24 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 |
| Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | baseline up to 24 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. |
| Overall Response of Partial Response (PR) or Greater. PR=at Least a 30% Decrease in the Sum of Diameters of Target Lesions, Taking as Reference the Baseline Sum Diameters | baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months | Overall Response (OR) of Partial Response (PR) or greater is based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria apply |
| Overall Survival (OS)- Kaplan-Meier Estimates of OS Timing in Months | baseline up to 24 months | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact |
| Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | baseline up to 30 months | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact |
| Overall Survival - Number of Participants With an Event | Every 8 Weeks until death, assessed up to 24 months | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact |
Countries
United States
Participant flow
Pre-assignment details
Prior to informed consent, patient was pre-identified to have activation of the P13K pathway confirmed via Genomic Profiling Report and whose disease had progressed on or after standard treatment
Participants by arm
| Arm | Count |
|---|---|
| BKM120 BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28- day cycle | 146 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 33 |
| Overall Study | Death | 3 |
| Overall Study | Disease Progression | 99 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | BKM120 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 51 Participants |
| Age, Categorical Between 18 and 65 years | 95 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 12.91 |
| ECOG Grade Grade 0 | 54 participants |
| ECOG Grade Grade 1 | 91 participants |
| ECOG Grade Grade 2 | 1 participants |
| Prior Lines of Antineoplastic Medications | 3 Number of prior lines of treatment |
| Protocol pre-defined gene mutation (by local labs) PIK3CA amplification | 19 participants |
| Protocol pre-defined gene mutation (by local labs) PIK3CA gene mutation | 74 participants |
| Protocol pre-defined gene mutation (by local labs) PIK3R1 gene mutation | 7 participants |
| Protocol pre-defined gene mutation (by local labs) PTEN gene mutation | 60 participants |
| Race/Ethnicity, Customized Asian | 3 participants |
| Race/Ethnicity, Customized Black | 7 participants |
| Race/Ethnicity, Customized Caucasian | 130 participants |
| Race/Ethnicity, Customized Other | 6 participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 141 / 146 |
| serious Total, serious adverse events | 59 / 146 |
Outcome results
Primary
Participant Clinical Benefit Response Rate
Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at \>=16 weeks. For hematologic tumors other appropriate hematological response criteria was applied. Response criteria: CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm., PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline
Time frame: Week 16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BKM120 | Participant Clinical Benefit Response Rate | 15.1 percentage of participants |
Secondary
Overall Response of Partial Response (PR) or Greater. PR=at Least a 30% Decrease in the Sum of Diameters of Target Lesions, Taking as Reference the Baseline Sum Diameters
Overall Response (OR) of Partial Response (PR) or greater is based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria apply
Time frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BKM120 | Overall Response of Partial Response (PR) or Greater. PR=at Least a 30% Decrease in the Sum of Diameters of Target Lesions, Taking as Reference the Baseline Sum Diameters | 1.4 percentage of patients |
Secondary
Overall Survival - Number of Participants With an Event
Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact
Time frame: Every 8 Weeks until death, assessed up to 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BKM120 | Overall Survival - Number of Participants With an Event | participants with an event | 110 participants |
| BKM120 | Overall Survival - Number of Participants With an Event | participants censored | 36 participants |
Secondary
Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages
Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact
Time frame: baseline up to 30 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 1 month | 97.3 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 2 months | 83.4 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 3 months | 73.5 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 4 months | 61.5 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 5 months | 60.1 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 6 months | 51.5 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 9 months | 41.3 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 12 months | 30.2 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 18 months | 18.6 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 24 months | 12.2 percentage of participants |
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages | 30 months | 12.2 percentage of participants |
Secondary
Overall Survival (OS)- Kaplan-Meier Estimates of OS Timing in Months
Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact
Time frame: baseline up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BKM120 | Overall Survival (OS)- Kaplan-Meier Estimates of OS Timing in Months | 6.3 months |
Secondary
Progression-Free Survival - Number of Participants With an Event
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BKM120 | Progression-Free Survival - Number of Participants With an Event | participants with an event | 112 participants |
| BKM120 | Progression-Free Survival - Number of Participants With an Event | participants censored | 34 participants |
Secondary
Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages
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: baseline up to 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 1 month | 88.4 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 2 months | 43.8 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 3 months | 39.4 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 4 months | 20.4 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 5 months | 20.4 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 6 months | 14.1 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 9 months | 5.8 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 12 months | 2.9 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 18 months | 1.4 percentage of participants |
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages | 24 months | 0.0 percentage of participants |
Secondary
Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Timing in 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: baseline up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BKM120 | Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Timing in Months | 1.9 months |