PIK3CA Mutated Advanced Solid Tumors, PIK3CA Amplified Advanced Solid Tumors
Conditions
Keywords
PIK3CA mutation, advanced solid tumor, breast cancer, ovarian cancer, cancers with a mass, bulky tumor, nodule, lump, advanced cancer, advanced solid malignancies
Brief summary
This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.
Detailed description
This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study were to be guided by a Bayesian Logistic Regression Model (BLRM). Once MTD/RP2D had been determined, patients were to be enrolled in two Phase II arms. Patients with PIK3CA mutated or amplified hormone receptor positive breast carcinoma were to be enrolled in Arm 1; patients with PIK3CA mutated or amplified ovarian carcinoma were to be enrolled in Arm 2. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.
Interventions
DRUGBYL719
BYL719 is a small molecule inhibiting PI3-Kinase.
DRUGAMG 479
AMG 479 is a monoclonal antibody directed against IGF1-R.
Sponsors
NantCell, Inc.
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
Key inclusion criteria: * Written informed consent. * Patients aged ≥ 18 years (male or female). * Patients with the following histologically/cytologically-confirmed advanced solid tumors with documented somatic PIK3CA mutations or amplifications in tumor tissue: * Hormone receptor positive breast carcinoma * Ovarian carcinoma * Other tumors upon agreement with sponsor * Adequate organ function * Negative serum pregnancy test Key
Exclusion criteria
* Patients with known history of severe infusion reactions to monoclonal antibodies. * Patients with primary CNS tumor or CNS tumor involvement. * History of thromboembolic event requiring full-dose anti-coagulation therapy any time prior to enrollment. * Clinically significant cardiac disease. * History of another malignancy within last 2 years. * Pregnant or nursing (lactating) women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) - Phase Ib | 28 days | Phase lb only |
| Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015) | The antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Overall response rate is defined as the proportion of patients who have a best overall response of complete response or partial response assessed per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013) | The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1 |
| Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015) | the antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter |
| Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib | Cycle 1 Day 1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose) | Area under curve for BYL719 (alpelisib) 1 cycle - 28 days of treatment |
| Cmax of BYL - Phase Ib | Cycle 1 Day 1, Cycle 1 Day 15 | Serum concentration for BYL719 (alpelisib) 1 cycle - 28 days of treatment |
| Cmax of AMG - Phase Ib | Cycle 1 Day 15 | Serum concentration for AMG 479 (ganitumab) 1 cycle - 28 days of treatment |
| Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib | Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose) | Area under curve for AMG 479 (ganitumab) 1 cycle - 28 days of treatment |
| Tmax and T Half of AMG - Phase Ib | Cycle 1 Day 15 | Tmax and half life of AMG 479 (ganitumab) 1 cycle - 28 days of treatment |
| Tmax and T Half of BYL - Phase Ib | Cycle 1 Day 1, Cycle 1 Day 15 | Tmax and half life of BYL719 (Alpelisib) 1 cycle - 28 days of treatment |
| Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013) | The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1 |
Countries
Belgium, Canada, Spain, United States
Participant flow
Pre-assignment details
Patients with selected advanced solid tumors who had relapsed or progressed on standard therapy were treated in BYL719X2105J study with a combination of alpelisib and ganitumab. Phase I of the trial was by dose combination of the treatment. Phase II was by patients.
Participants by arm
| Arm | Count |
|---|---|
| BYL 200mg + AMG 12mg/kg BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors | 4 |
| BYL 300mg + AMG 12mg/kg BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors | 10 |
| BYL 350mg + AMG 12mg/kg BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors | 10 |
| HR+BC - Phase II Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breast carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg. | 16 |
| Ovarian - Phase II Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg | 6 |
| Non-HR+BC/Ovarian - Phase II Patients with other than Breast and Ovarian cancer treated in the phase II part | 1 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Administrative problems | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse Event | 1 | 3 | 4 | 2 | 3 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Disease progression | 3 | 5 | 5 | 13 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | BYL 200mg + AMG 12mg/kg | BYL 300mg + AMG 12mg/kg | BYL 350mg + AMG 12mg/kg | HR+BC - Phase II | Ovarian - Phase II | Non-HR+BC/Ovarian - Phase II | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.5 years STANDARD_DEVIATION 3.11 | 57.5 years STANDARD_DEVIATION 15.55 | 63.7 years STANDARD_DEVIATION 7.83 | 51.3 years STANDARD_DEVIATION 8.04 | 59.7 years STANDARD_DEVIATION 6.53 | 56.0 years STANDARD_DEVIATION 0 | 56.3 years STANDARD_DEVIATION 10.54 |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Caucasian | 2 Participants | 8 Participants | 10 Participants | 14 Participants | 5 Participants | 1 Participants | 40 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 7 Participants | 15 Participants | 6 Participants | 1 Participants | 40 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 8 / 10 | 8 / 10 | 13 / 16 | 5 / 6 |
| other Total, other adverse events | 4 / 4 | 10 / 10 | 10 / 10 | 16 / 16 | 6 / 6 |
| serious Total, serious adverse events | 1 / 4 | 5 / 10 | 5 / 10 | 9 / 16 | 5 / 6 |
Outcome results
Primary
Dose Limiting Toxicities (DLTs) - Phase Ib
Phase lb only
Time frame: 28 days
Population: Dose determining set (DDS): DDS includes all patients from the safety set who either met the minimum treatment exposure and safety evaluation requirements without experiencing DLT within Cycle 1 or experienced a DLT at any time during Cycle 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Drug hypersensitivity | 0 Participants |
| BYL 200mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Hyperglycemia | 0 Participants |
| BYL 200mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Rash maculopapular | 0 Participants |
| BYL 200mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Urticaria | 0 Participants |
| BYL 300mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Urticaria | 1 Participants |
| BYL 300mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Drug hypersensitivity | 0 Participants |
| BYL 300mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Rash maculopapular | 1 Participants |
| BYL 300mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Hyperglycemia | 0 Participants |
| BYL 350mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Urticaria | 0 Participants |
| BYL 350mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Hyperglycemia | 1 Participants |
| BYL 350mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Rash maculopapular | 0 Participants |
| BYL 350mg + AMG 12mg/kg | Dose Limiting Toxicities (DLTs) - Phase Ib | Drug hypersensitivity | 1 Participants |
Primary
Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
The antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Overall response rate is defined as the proportion of patients who have a best overall response of complete response or partial response assessed per RECIST 1.1.
Time frame: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
Population: Full analysis set (FAS). The full analysis set (FAS) includes all patients who received at least one full or partial dose of alpelisib or ganitumab. Patients were analyzed according to the planned treatment combination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BYL 200mg + AMG 12mg/kg | Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | 12.5 Percentages of participants |
| BYL 300mg + AMG 12mg/kg | Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | 16.7 Percentages of participants |
| BYL 350mg + AMG 12mg/kg | Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | 13.0 Percentages of participants |
Secondary
Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib
Area under curve for BYL719 (alpelisib) 1 cycle - 28 days of treatment
Time frame: Cycle 1 Day 1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)
Population: Pharmacokinetic analysis set (PAS). The PAS included all patients who had at least one blood sample providing evaluable PK data. Patients were analyzed according to the dose level they actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib | Cycle 1 Day 1 | 19900 hr*ng/mL | Standard Deviation 8700 |
| BYL 200mg + AMG 12mg/kg | Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib | Cycle 1 day 15 | 24000 hr*ng/mL | Standard Deviation 10700 |
| BYL 300mg + AMG 12mg/kg | Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib | Cycle 1 Day 1 | 23400 hr*ng/mL | Standard Deviation 10500 |
| BYL 300mg + AMG 12mg/kg | Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib | Cycle 1 day 15 | 29700 hr*ng/mL | Standard Deviation 9170 |
| BYL 350mg + AMG 12mg/kg | Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib | Cycle 1 Day 1 | 25200 hr*ng/mL | Standard Deviation 9200 |
| BYL 350mg + AMG 12mg/kg | Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib | Cycle 1 day 15 | 25200 hr*ng/mL | Standard Deviation 9160 |
Secondary
Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib
Area under curve for AMG 479 (ganitumab) 1 cycle - 28 days of treatment
Time frame: Cycle 1 Day 15 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose)
Population: Pharmacokinetic analysis set (PAS). The PAS included all patients who had at least one blood sample providing evaluable PK data. Patients were analyzed according to the dose level they actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib | 22900 hr*ng/mL | Standard Deviation 3930 |
| BYL 300mg + AMG 12mg/kg | Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib | 22500 hr*ng/mL | Standard Deviation 7040 |
| BYL 350mg + AMG 12mg/kg | Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib | 25200 hr*ng/mL | Standard Deviation 8000 |
Secondary
Cmax of AMG - Phase Ib
Serum concentration for AMG 479 (ganitumab) 1 cycle - 28 days of treatment
Time frame: Cycle 1 Day 15
Population: Pharmacokinetic analysis set (PAS). The PAS included all patients who had at least one blood sample providing evaluable PK data. Patients were analyzed according to the dose level they actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Cmax of AMG - Phase Ib | 192 ng/mL | Standard Deviation 24 |
| BYL 300mg + AMG 12mg/kg | Cmax of AMG - Phase Ib | 202 ng/mL | Standard Deviation 43.3 |
| BYL 350mg + AMG 12mg/kg | Cmax of AMG - Phase Ib | 232 ng/mL | Standard Deviation 59.3 |
Secondary
Cmax of BYL - Phase Ib
Serum concentration for BYL719 (alpelisib) 1 cycle - 28 days of treatment
Time frame: Cycle 1 Day 1, Cycle 1 Day 15
Population: Pharmacokinetic analysis set (PAS). The PAS included all patients who had at least one blood sample providing evaluable PK data. Patients were analyzed according to the dose level they actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Cmax of BYL - Phase Ib | Cycle 1 Day 1 | 2070 ng/mL | Standard Deviation 1040 |
| BYL 200mg + AMG 12mg/kg | Cmax of BYL - Phase Ib | Cycle 1 day 15 | 3080 ng/mL | Standard Deviation 1750 |
| BYL 300mg + AMG 12mg/kg | Cmax of BYL - Phase Ib | Cycle 1 Day 1 | 2620 ng/mL | Standard Deviation 1260 |
| BYL 300mg + AMG 12mg/kg | Cmax of BYL - Phase Ib | Cycle 1 day 15 | 2880 ng/mL | Standard Deviation 910 |
| BYL 350mg + AMG 12mg/kg | Cmax of BYL - Phase Ib | Cycle 1 Day 1 | 2640 ng/mL | Standard Deviation 888 |
| BYL 350mg + AMG 12mg/kg | Cmax of BYL - Phase Ib | Cycle 1 day 15 | 2600 ng/mL | Standard Deviation 1040 |
Secondary
Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib
The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1
Time frame: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
Population: Full Analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Progressive disease (PD) | 3 Participants |
| BYL 200mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Stable disease (PD) | 1 Participants |
| BYL 200mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Complete response (CR) | 0 Participants |
| BYL 200mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Partial response (PR) | 0 Participants |
| BYL 200mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Unknown | 0 Participants |
| BYL 300mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Stable disease (PD) | 3 Participants |
| BYL 300mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Complete response (CR) | 0 Participants |
| BYL 300mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Partial response (PR) | 0 Participants |
| BYL 300mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Progressive disease (PD) | 3 Participants |
| BYL 300mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Unknown | 4 Participants |
| BYL 350mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Unknown | 2 Participants |
| BYL 350mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Progressive disease (PD) | 3 Participants |
| BYL 350mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Complete response (CR) | 0 Participants |
| BYL 350mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Stable disease (PD) | 2 Participants |
| BYL 350mg + AMG 12mg/kg | Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib | Partial response (PR) | 3 Participants |
Secondary
Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
the antitumor activity of alpelisib in combination with ganitumab in patients with PIK3CA mutated or amplified hormone receptor positive (HR+) breast (arm 1) or ovarian (arm 2) cancer. Phase II only, Cycle 1 Day 1 through Cycle 6 Day 28; assessed at baseline and every 8 weeks thereafter
Time frame: Approximately 1 year (since initiation of Phase II, Dec 2013, till Primary CSR cut off 06Jan2015)
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BYL 200mg + AMG 12mg/kg | Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | 43.8 Percentages of participants |
| BYL 300mg + AMG 12mg/kg | Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | 50.0 Percentages of participants |
| BYL 350mg + AMG 12mg/kg | Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II | 47.8 Percentages of participants |
Secondary
Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib
The anti-tumor activity of alpelisib and ganitumab in combination as per RECIST 1.1
Time frame: Approximately 1 year (since FPFV 27Nov2012, till MTD declaration 26Nov2013)
Population: Full Analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BYL 200mg + AMG 12mg/kg | Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib | 25.0 Percentages of participants |
| BYL 300mg + AMG 12mg/kg | Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib | 9.1 Percentages of participants |
| BYL 350mg + AMG 12mg/kg | Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib | 50.0 Percentages of participants |
Secondary
Tmax and T Half of AMG - Phase Ib
Tmax and half life of AMG 479 (ganitumab) 1 cycle - 28 days of treatment
Time frame: Cycle 1 Day 15
Population: Pharmacokinetic analysis set (PAS). The PAS included all patients who had at least one blood sample providing evaluable PK data. Patients were analyzed according to the dose level they actually received.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Tmax and T Half of AMG - Phase Ib | Tmax | 21.20 hr |
| BYL 200mg + AMG 12mg/kg | Tmax and T Half of AMG - Phase Ib | Thalf | 132 hr |
| BYL 300mg + AMG 12mg/kg | Tmax and T Half of AMG - Phase Ib | Thalf | 117 hr |
| BYL 300mg + AMG 12mg/kg | Tmax and T Half of AMG - Phase Ib | Tmax | 1.02 hr |
| BYL 350mg + AMG 12mg/kg | Tmax and T Half of AMG - Phase Ib | Thalf | 180 hr |
| BYL 350mg + AMG 12mg/kg | Tmax and T Half of AMG - Phase Ib | Tmax | 1.07 hr |
Secondary
Tmax and T Half of BYL - Phase Ib
Tmax and half life of BYL719 (Alpelisib) 1 cycle - 28 days of treatment
Time frame: Cycle 1 Day 1, Cycle 1 Day 15
Population: Pharmacokinetic analysis set (PAS). The PAS included all patients who had at least one blood sample providing evaluable PK data. Patients were analyzed according to the dose level they actually received.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BYL 200mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Tmax (Cycle 1 Day 1) | 2.78 hr |
| BYL 200mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Tmax (Cycle 1 Day 15) | 1.57 hr |
| BYL 200mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Thalf (Cycle 1 Day 1) | 7.78 hr |
| BYL 200mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Thalf (Cycle 1 Day15) | 6.89 hr |
| BYL 300mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Thalf (Cycle 1 Day15) | 6.80 hr |
| BYL 300mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Tmax (Cycle 1 Day 1) | 1.97 hr |
| BYL 300mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Thalf (Cycle 1 Day 1) | 6.06 hr |
| BYL 300mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Tmax (Cycle 1 Day 15) | 3.01 hr |
| BYL 350mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Thalf (Cycle 1 Day15) | 6.83 hr |
| BYL 350mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Tmax (Cycle 1 Day 15) | 2.02 hr |
| BYL 350mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Thalf (Cycle 1 Day 1) | 6.86 hr |
| BYL 350mg + AMG 12mg/kg | Tmax and T Half of BYL - Phase Ib | Tmax (Cycle 1 Day 1) | 2.36 hr |