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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Novartis Investigative Site
Los Angeles, California, United States
Novartis Investigative Site
Boston, Massachusetts, United States
Novartis Investigative Site
New York, New York, United States
Novartis Investigative Site
Nashville, Tennessee, United States
Novartis Investigative Site
Leuven, Belgium
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Seville, Andalusia, Spain
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
Madrid, Spain
Novartis Investigative Site
Madrid, Spain
Dose Limiting Toxicities (DLTs) - Phase Ib
Phase lb only
Time frame: 28 days
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)
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)
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)
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)
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
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)
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
Cmax of AMG - Phase Ib
Serum concentration for AMG 479 (ganitumab) 1 cycle - 28 days of treatment
Time frame: Cycle 1 Day 15
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)
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
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