Non-small Cell Lung Cancer
Conditions
Keywords
NSCLC, PI3K
Brief summary
The purpose of this two-stage phase II study is to assess the efficacy of BKM120, as measured by determining the progression free survival (PFS), in patients with pretreated metastatic Non-small Cell Lung Cancer (NSCLC) that exhibits PI3K pathway activation. BKM120 will be investigated in two groups of NSCLC patients according to the histology of the cancer: squamous and non-squamous.
Interventions
DRUGBKM120
Buparlisib was supplied as 10mg or 50mg capsules. It was administered on a continuous once daily dosing schedule at a dose of 100 mg. The patient was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed NSCLC with activated PI3K pathway * Progressive disease after prior systemic antineoplastic treatment(s) for advanced NSCLC * Archival or fresh tumor biopsy must be available for profiling * Measurable and/or non-measurable disease as per RECIST 1.1 criteria * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Adequate organ function as assessed by laboratory tests
Exclusion criteria
* Patient has received previous treatment with PI3K inhibitors * Patient with squamous NSCLC has received more than one line of chemotherapy treatment for metastatic disease; patient with non-squamous NSCLC has received more than two lines of systemic antineoplastic treatment for metastatic disease * Uncontrolled or symptomatic CNS metastases * Concurrent use of any other approved or investigational antineoplastic agent * Radiotherapy ≤ 28 days prior to starting study drug * Major surgery within 28 days prior to starting study drug * History of clinically significant cardiac dysfunction, mood disorders, or poorly controlled diabetes mellitus * Current treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes * Impairment of gastrointestinal (GI) function * Chronic treatment with steroids or another immunosuppressive agent. * Concurrent severe and/or uncontrolled medical condition * Currently receiving Warfarin or another coumarin derivative * Known history of HIV infection * Sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality) * Pregnancy, lactation, or breastfeeding * Woman of child-bearing potential Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12 | Week 12 | PFS rate was defined as the percentage of participants who were progression free at 12 weeks. Participants were considered as a success for PFS rate evaluated at 12 weeks if they presented an overall response at their 2nd post-baseline tumor assessment.The enrollment into the study in either histology group would stop for futility if a PFS rate \<50% at 12 weeks was observed. No statistical analysis was planned for this primary outcome. The results of the primary objective was based on the data from the interim analysis that took place at the cut off dates: 10-Apr-2013 for non-squamous and 08-Jan-2014 for squamous group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Using Kaplan-Meier Estimates | Every 8 weeks up to 24 months | OS was defined as the time from start of study drug (Stage 1) until death from any cause. If a patient was not known to have died, survival was censored at the date of last contact. |
| Overall Response Rate (ORR) Based on Investigator Assessment | Every 6 weeks up to 24 months | ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). ORR included all patients with and without measurable disease at baseline. |
| Disease Control Rate (DCR) | Every 6 weeks up tp 24 months | DCR defined as the percentage of participants with best overall response of CR or PR or stable disease (SD). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). DCR included all participants with and without measurable disease at baseline. |
| Time to Response (TTR) | Every 6 weeks up to 24 months | TTR for a participant was defined as the time from the first treatment date to the date of first documented confirmed CR or PR evaluation. The date of event was defined as the date of response that was first determined and not using the date the response was confirmed. |
| Duration of Response (DoR) | Every 6 weeks up to 24 months | DoR was defined as the elapsed time between the date of first documented CR or PR response (not the date of confirmed response) and the following date of event defined as the first documented progression or death due to underlying cancer. |
Countries
Argentina, Belgium, Brazil, Canada, France, Germany, Hong Kong, Hungary, Italy, Japan, Netherlands, Singapore, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Squamous BKM120 100mg qd Diagnosed patients with non-small cell lung cancer (NSCLC) that progressed after one prior, platinum-based chemotherapy line for metastatic disease. | 30 |
| Non-Squamous BKM120 100mg qd Diagnosed patients with non-squamous NSCLC that progressed after one or two prior antineoplastic therapy lines for metastatic disease. | 33 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 6 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Patient/Guardian decision | 3 | 4 |
| Overall Study | Physician Decision | 3 | 2 |
| Overall Study | Progressive disease | 11 | 20 |
Baseline characteristics
| Characteristic | Squamous BKM120 100mg qd | Non-Squamous BKM120 100mg qd | Total |
|---|---|---|---|
| Age, Customized < 65 years | 12 Participants | 19 Participants | 31 Participants |
| Age, Customized >= 65 years | 18 Participants | 14 Participants | 32 Participants |
| Sex: Female, Male Female | 9 Participants | 14 Participants | 23 Participants |
| Sex: Female, Male Male | 21 Participants | 19 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 30 | 32 / 33 |
| serious Total, serious adverse events | 16 / 30 | 15 / 33 |
Outcome results
Primary
Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12
PFS rate was defined as the percentage of participants who were progression free at 12 weeks. Participants were considered as a success for PFS rate evaluated at 12 weeks if they presented an overall response at their 2nd post-baseline tumor assessment.The enrollment into the study in either histology group would stop for futility if a PFS rate \<50% at 12 weeks was observed. No statistical analysis was planned for this primary outcome. The results of the primary objective was based on the data from the interim analysis that took place at the cut off dates: 10-Apr-2013 for non-squamous and 08-Jan-2014 for squamous group.
Time frame: Week 12
Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Squamous BKM120 100mg qd | Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12 | 23.3 Percentage of participants |
| Non-Squamous BKM120 100mg qd | Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12 | 20.0 Percentage of participants |
Secondary
Disease Control Rate (DCR)
DCR defined as the percentage of participants with best overall response of CR or PR or stable disease (SD). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). DCR included all participants with and without measurable disease at baseline.
Time frame: Every 6 weeks up tp 24 months
Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Squamous BKM120 100mg qd | Disease Control Rate (DCR) | 46.7 Percentage of participants |
| Non-Squamous BKM120 100mg qd | Disease Control Rate (DCR) | 45.5 Percentage of participants |
Secondary
Duration of Response (DoR)
DoR was defined as the elapsed time between the date of first documented CR or PR response (not the date of confirmed response) and the following date of event defined as the first documented progression or death due to underlying cancer.
Time frame: Every 6 weeks up to 24 months
Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least 1 dose of study drug. 1 partial response was observed as best overall response (BOR) for 1 patient in the squamous group. Also,1 patient experienced partial response as BOR in the non-squamous group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Squamous BKM120 100mg qd | Duration of Response (DoR) | 73 Days |
| Non-Squamous BKM120 100mg qd | Duration of Response (DoR) | 85 Days |
Secondary
Overall Response Rate (ORR) Based on Investigator Assessment
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). ORR included all patients with and without measurable disease at baseline.
Time frame: Every 6 weeks up to 24 months
Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Squamous BKM120 100mg qd | Overall Response Rate (ORR) Based on Investigator Assessment | 3.3 Percentage of participants |
| Non-Squamous BKM120 100mg qd | Overall Response Rate (ORR) Based on Investigator Assessment | 3.0 Percentage of participants |
Secondary
Overall Survival (OS) Using Kaplan-Meier Estimates
OS was defined as the time from start of study drug (Stage 1) until death from any cause. If a patient was not known to have died, survival was censored at the date of last contact.
Time frame: Every 8 weeks up to 24 months
Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Squamous BKM120 100mg qd | Overall Survival (OS) Using Kaplan-Meier Estimates | 7.98 Months |
| Non-Squamous BKM120 100mg qd | Overall Survival (OS) Using Kaplan-Meier Estimates | 7.20 Months |
Secondary
Time to Response (TTR)
TTR for a participant was defined as the time from the first treatment date to the date of first documented confirmed CR or PR evaluation. The date of event was defined as the date of response that was first determined and not using the date the response was confirmed.
Time frame: Every 6 weeks up to 24 months
Population: Analysis set Stage 1 includes all patients who were enrolled during Stage 1 after meeting eligibility criteria and who have received at least 1 dose of study drug. 1 partial response was observed as best overall response (BOR) for 1 patient in the squamous group. Also,1 patient experienced partial response as BOR in the non-squamous group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Squamous BKM120 100mg qd | Time to Response (TTR) | 41 Days |
| Non-Squamous BKM120 100mg qd | Time to Response (TTR) | 42 Days |