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A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT01708161
Collaborator
NantCell, Inc. (Industry)
47
Enrollment
10
Locations
1
Arm
54.1
Actual Duration (Months)
4.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors
Actual Study Start Date :
Nov 27, 2012
Actual Primary Completion Date :
Dec 26, 2014
Actual Study Completion Date :
Jun 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: BYL719 + AMG 479

For: Dose escalation phase/Phase II Expansion Phase. Cohorts of 3-6 patients were to be enrolled sequentially until an MTD or a recommended Phase II dose were defined. All patients were to receive the combination treatment. Sequential cohorts may receive different doses of the combination. In the Phase II expansion, all patients were to receive the same combination treatment.

Drug: BYL719
BYL719 is a small molecule inhibiting PI3-Kinase.
Other Names:
  • ALPELISIB

    • Drug: AMG 479
    AMG 479 is a monoclonal antibody directed against IGF1-R.
    Other Names:
  • ganitumab

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicities (DLTs) - Phase Ib [28 days]

      Phase lb only

    2. 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 Outcome Measures

    1. 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

    2. 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

    3. 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

    4. Cmax of BYL - Phase Ib [Cycle 1 Day 1, Cycle 1 Day 15]

      Serum concentration for BYL719 (alpelisib) 1 cycle - 28 days of treatment

    5. 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

    6. 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

    7. Cmax of AMG - Phase Ib [Cycle 1 Day 15]

      Serum concentration for AMG 479 (ganitumab) 1 cycle - 28 days of treatment

    8. 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

    9. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Los Angeles California United States 90095
    2 Novartis Investigative Site Boston Massachusetts United States 02114
    3 Novartis Investigative Site New York New York United States 10017
    4 Novartis Investigative Site Nashville Tennessee United States 37203
    5 Novartis Investigative Site Leuven Belgium 3000
    6 Novartis Investigative Site Toronto Ontario Canada M5G 1Z6
    7 Novartis Investigative Site Sevilla Andalucia Spain 41013
    8 Novartis Investigative Site Barcelona Catalunya Spain 08035
    9 Novartis Investigative Site Madrid Spain 28033
    10 Novartis Investigative Site Madrid Spain 28041

    Sponsors and Collaborators

    • Novartis Pharmaceuticals
    • NantCell, Inc.

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01708161
    Other Study ID Numbers:
    • CBYL719X2105J
    • 2012-001962-13
    First Posted:
    Oct 16, 2012
    Last Update Posted:
    Sep 13, 2018
    Last Verified:
    Aug 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    PIK3CA mutation
    advanced solid tumor
    breast cancer
    ovarian cancer
    cancers with a mass
    bulky tumor
    nodule
    lump
    advanced cancer
    advanced solid malignancies
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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.
    Arm/Group Title 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
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors 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. Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg Patients with other than Breast and Ovarian cancer treated in the phase II part
    Period Title: Overall Study
    STARTED 4 10 10 16 6 1
    COMPLETED 0 0 0 0 0 0
    NOT COMPLETED 4 10 10 16 6 1

    Baseline Characteristics

    Arm/Group Title 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
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors 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. Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg Patients with other than Breast and Ovarian cancer treated in the phase II part Total of all reporting groups
    Overall Participants 4 10 10 16 6 1 47
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    50.5
    (3.11)
    57.5
    (15.55)
    63.7
    (7.83)
    51.3
    (8.04)
    59.7
    (6.53)
    56.0
    (0)
    56.3
    (10.54)
    Sex: Female, Male (Count of Participants)
    Female
    4
    100%
    7
    70%
    7
    70%
    15
    93.8%
    6
    100%
    1
    100%
    40
    85.1%
    Male
    0
    0%
    3
    30%
    3
    30%
    1
    6.3%
    0
    0%
    0
    0%
    7
    14.9%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    2
    50%
    8
    80%
    10
    100%
    14
    87.5%
    5
    83.3%
    1
    100%
    40
    85.1%
    Asian
    2
    50%
    2
    20%
    0
    0%
    2
    12.5%
    0
    0%
    0
    0%
    6
    12.8%
    Native American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    1
    2.1%

    Outcome Measures

    1. Primary Outcome
    Title Dose Limiting Toxicities (DLTs) - Phase Ib
    Description Phase lb only
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    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/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 3 8 9
    Drug hypersensitivity
    0
    0%
    0
    0%
    1
    10%
    Hyperglycemia
    0
    0%
    0
    0%
    1
    10%
    Rash maculopapular
    0
    0%
    1
    10%
    0
    0%
    Urticaria
    0
    0%
    1
    10%
    0
    0%
    2. Primary Outcome
    Title Percentage of Patients With Overall Response Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title HR+BC - Phase II Ovarian - Phase II All Patients - Phase
    Arm/Group Description 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. Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg The total column "All patients" includes a patient with non-HR+BC and non-Ovarian cancer treated in the Phase II part.
    Measure Participants 16 6 23
    Number (95% Confidence Interval) [Percentages of participants]
    12.5
    312.5%
    16.7
    167%
    13.0
    130%
    3. Secondary Outcome
    Title Number of Patients With Best Overall Response (RECIST) Based on Investigator Radiology Assessment - Phase Ib
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis set
    Arm/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 10 10
    Complete response (CR)
    0
    0%
    0
    0%
    0
    0%
    Partial response (PR)
    0
    0%
    0
    0%
    3
    30%
    Stable disease (PD)
    1
    25%
    3
    30%
    2
    20%
    Progressive disease (PD)
    3
    75%
    3
    30%
    3
    30%
    Unknown
    0
    0%
    4
    40%
    2
    20%
    4. Secondary Outcome
    Title Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment - Phase Ib
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis set
    Arm/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 33 10
    Number (95% Confidence Interval) [Percentages of participants]
    25.0
    625%
    9.1
    91%
    50.0
    500%
    5. Secondary Outcome
    Title Percentage of Patients With Disease Control Rate (RECIST) Based on Investigator Radiology Assessment for HR Positive Breast and Ovarian Cancer - Phase II
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title HR+BC - Phase II Ovarian - Phase II All Patients - Phase II
    Arm/Group Description 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. Patients with PIK3CA mutated or amplified ovarian cancer were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg The total column "All patients" includes a patient with non-HR+BC and non-Ovarian cancer treated in the Phase II part.
    Measure Participants 16 6 23
    Number (95% Confidence Interval) [Percentages of participants]
    43.8
    1095%
    50.0
    500%
    47.8
    478%
    6. Secondary Outcome
    Title Cmax of BYL - Phase Ib
    Description Serum concentration for BYL719 (alpelisib) 1 cycle - 28 days of treatment
    Time Frame Cycle 1 Day 1, Cycle 1 Day 15

    Outcome Measure Data

    Analysis Population Description
    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/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 10 10
    Cycle 1 Day 1
    2070
    (1040)
    2620
    (1260)
    2640
    (888)
    Cycle 1 day 15
    3080
    (1750)
    2880
    (910)
    2600
    (1040)
    7. Secondary Outcome
    Title Area Under Curve (AUC) 0-24 Hour of BYL - Phase Ib
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 10 10
    Cycle 1 Day 1
    19900
    (8700)
    23400
    (10500)
    25200
    (9200)
    Cycle 1 day 15
    24000
    (10700)
    29700
    (9170)
    25200
    (9160)
    8. Secondary Outcome
    Title Tmax and T Half of BYL - Phase Ib
    Description Tmax and half life of BYL719 (Alpelisib) 1 cycle - 28 days of treatment
    Time Frame Cycle 1 Day 1, Cycle 1 Day 15

    Outcome Measure Data

    Analysis Population Description
    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/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 10 10
    Tmax (Cycle 1 Day 1)
    2.78
    1.97
    2.36
    Tmax (Cycle 1 Day 15)
    1.57
    3.01
    2.02
    Thalf (Cycle 1 Day 1)
    7.78
    6.06
    6.86
    Thalf (Cycle 1 Day15)
    6.89
    6.80
    6.83
    9. Secondary Outcome
    Title Cmax of AMG - Phase Ib
    Description Serum concentration for AMG 479 (ganitumab) 1 cycle - 28 days of treatment
    Time Frame Cycle 1 Day 15

    Outcome Measure Data

    Analysis Population Description
    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/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 10 10
    Mean (Standard Deviation) [ng/mL]
    192
    (24)
    202
    (43.3)
    232
    (59.3)
    10. Secondary Outcome
    Title Area Under Curve (AUC) 0-336 Hour of AMG - Phase Ib
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 10 10
    Mean (Standard Deviation) [hr*ng/mL]
    22900
    (3930)
    22500
    (7040)
    25200
    (8000)
    11. Secondary Outcome
    Title Tmax and T Half of AMG - Phase Ib
    Description Tmax and half life of AMG 479 (ganitumab) 1 cycle - 28 days of treatment
    Time Frame Cycle 1 Day 15

    Outcome Measure Data

    Analysis Population Description
    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/Group Title BYL 200mg + AMG 12mg/kg BYL 300mg + AMG 12mg/kg BYL 350mg + AMG 12mg/kg
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors
    Measure Participants 4 10 10
    Tmax
    21.20
    1.02
    1.07
    Thalf
    132
    117
    180

    Adverse Events

    Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 4.5 years.
    Adverse Event Reporting Description One patients with a tumor type other than Breast and Ovarian treated in the phase II part not represented.
    Arm/Group Title BYL 200mg + AMG 12 mg/kg BYL 300mg + AMG 12 mg/kg BYL 350mg + AMG 12 mg/kg HR + BC - Phase II Ovarian - Phase II
    Arm/Group Description BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors BYL719 (alpelisib) and AMG 479 (ganitumab) regimen in patients with PIK3CA mutated or amplified solid tumors Patients with PIK3CA mutated or amplified hormone receptor (HR) positive breat carcinoma (BC) were treated with alpelisib 300 mg once daily and ganitumab 12 mg/kg Patients with other than Breast and Ovarian cancer treated in the phase II
    All Cause Mortality
    BYL 200mg + AMG 12 mg/kg BYL 300mg + AMG 12 mg/kg BYL 350mg + AMG 12 mg/kg HR + BC - Phase II Ovarian - Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 8/10 (80%) 8/10 (80%) 13/16 (81.3%) 5/6 (83.3%)
    Serious Adverse Events
    BYL 200mg + AMG 12 mg/kg BYL 300mg + AMG 12 mg/kg BYL 350mg + AMG 12 mg/kg HR + BC - Phase II Ovarian - Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/4 (25%) 5/10 (50%) 5/10 (50%) 9/16 (56.3%) 5/6 (83.3%)
    Blood and lymphatic system disorders
    Neutropenia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Ascites 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Large intestinal obstruction 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    General disorders
    Asthenia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 1/6 (16.7%)
    Fatigue 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pyrexia 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Hepatobiliary disorders
    Bile duct stenosis 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Bile duct stone 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Immune system disorders
    Drug hypersensitivity 1/4 (25%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Infections and infestations
    Abdominal abscess 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Escherichia sepsis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Lung infection 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Respiratory tract infection 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Subcutaneous abscess 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Injury, poisoning and procedural complications
    Fracture displacement 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Investigations
    Blood creatinine increased 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Metabolism and nutrition disorders
    Dehydration 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Hypercalcaemia 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Hyperglycaemia 0/4 (0%) 0/10 (0%) 1/10 (10%) 2/16 (12.5%) 3/6 (50%)
    Hyperuricaemia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Musculoskeletal and connective tissue disorders
    Myositis 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Nervous system disorders
    Convulsion 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Generalised tonic-clonic seizure 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Renal and urinary disorders
    Renal failure acute 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Urinary retention 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Reproductive system and breast disorders
    Female genital tract fistula 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute interstitial pneumonitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pleural effusion 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pleuritic pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pneumothorax 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Respiratory failure 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Vascular disorders
    Deep vein thrombosis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Other (Not Including Serious) Adverse Events
    BYL 200mg + AMG 12 mg/kg BYL 300mg + AMG 12 mg/kg BYL 350mg + AMG 12 mg/kg HR + BC - Phase II Ovarian - Phase II
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 10/10 (100%) 10/10 (100%) 16/16 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/4 (0%) 2/10 (20%) 0/10 (0%) 2/16 (12.5%) 3/6 (50%)
    Leukocytosis 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Lymph node pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Neutropenia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Thrombocytopenia 0/4 (0%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Cardiac disorders
    Bradycardia 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Palpitations 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 2/6 (33.3%)
    Ear and labyrinth disorders
    Ear congestion 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 0/6 (0%)
    Ear pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hearing impaired 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Tinnitus 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Endocrine disorders
    Hypothyroidism 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Eye disorders
    Eye swelling 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Eyelid ptosis 1/4 (25%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Periorbital oedema 1/4 (25%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Photopsia 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Vision blurred 1/4 (25%) 2/10 (20%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Abdominal distension 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 0/6 (0%)
    Abdominal pain 0/4 (0%) 1/10 (10%) 2/10 (20%) 3/16 (18.8%) 2/6 (33.3%)
    Abdominal pain lower 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Abdominal pain upper 1/4 (25%) 1/10 (10%) 2/10 (20%) 1/16 (6.3%) 1/6 (16.7%)
    Anal fissure 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Anal ulcer 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Anorectal discomfort 0/4 (0%) 0/10 (0%) 2/10 (20%) 0/16 (0%) 0/6 (0%)
    Aphthous stomatitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Chapped lips 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Constipation 0/4 (0%) 3/10 (30%) 2/10 (20%) 4/16 (25%) 1/6 (16.7%)
    Diarrhoea 2/4 (50%) 5/10 (50%) 7/10 (70%) 10/16 (62.5%) 3/6 (50%)
    Dry mouth 1/4 (25%) 2/10 (20%) 3/10 (30%) 3/16 (18.8%) 1/6 (16.7%)
    Dyspepsia 1/4 (25%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 3/6 (50%)
    Dysphagia 0/4 (0%) 0/10 (0%) 1/10 (10%) 2/16 (12.5%) 0/6 (0%)
    Flatulence 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Gastrooesophageal reflux disease 0/4 (0%) 1/10 (10%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Gingival bleeding 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Gingival erosion 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Gingival recession 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Haemorrhoids 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Mouth ulceration 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Nausea 0/4 (0%) 9/10 (90%) 5/10 (50%) 7/16 (43.8%) 3/6 (50%)
    Odynophagia 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Oesophagitis 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Oral pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Retching 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Sensitivity of teeth 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Small intestinal obstruction 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Stomatitis 3/4 (75%) 3/10 (30%) 5/10 (50%) 6/16 (37.5%) 3/6 (50%)
    Toothache 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Vomiting 0/4 (0%) 6/10 (60%) 4/10 (40%) 4/16 (25%) 3/6 (50%)
    General disorders
    Asthenia 0/4 (0%) 2/10 (20%) 2/10 (20%) 3/16 (18.8%) 3/6 (50%)
    Axillary pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Catheter site pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Chills 1/4 (25%) 1/10 (10%) 2/10 (20%) 3/16 (18.8%) 1/6 (16.7%)
    Face oedema 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Fatigue 2/4 (50%) 6/10 (60%) 8/10 (80%) 7/16 (43.8%) 2/6 (33.3%)
    Feeling abnormal 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Feeling cold 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Gait disturbance 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Injection site rash 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Instillation site pain 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Localised oedema 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Malaise 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Mucosal inflammation 0/4 (0%) 0/10 (0%) 0/10 (0%) 3/16 (18.8%) 0/6 (0%)
    Non-cardiac chest pain 0/4 (0%) 0/10 (0%) 1/10 (10%) 3/16 (18.8%) 1/6 (16.7%)
    Oedema peripheral 0/4 (0%) 2/10 (20%) 1/10 (10%) 1/16 (6.3%) 0/6 (0%)
    Pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pyrexia 0/4 (0%) 0/10 (0%) 1/10 (10%) 4/16 (25%) 1/6 (16.7%)
    Thirst 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hepatobiliary disorders
    Cholangitis 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Immune system disorders
    Drug hypersensitivity 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Hypersensitivity 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Seasonal allergy 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Infections and infestations
    Abscess limb 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Bronchitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Cellulitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Conjunctivitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Gastroenteritis viral 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Gingivitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Herpes virus infection 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Localised infection 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 1/6 (16.7%)
    Nail infection 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Nasal herpes 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Nasopharyngitis 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 1/6 (16.7%)
    Onychomycosis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Oral candidiasis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Paronychia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Periorbital cellulitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pharyngitis 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Rash pustular 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Subcutaneous abscess 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Upper respiratory tract infection 0/4 (0%) 1/10 (10%) 0/10 (0%) 2/16 (12.5%) 1/6 (16.7%)
    Urinary tract infection 0/4 (0%) 0/10 (0%) 0/10 (0%) 3/16 (18.8%) 0/6 (0%)
    Vulvovaginal mycotic infection 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Injury, poisoning and procedural complications
    Contusion 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Fall 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hip fracture 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Infusion related reaction 1/4 (25%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Wound 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Wound complication 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Alanine aminotransferase increased 0/4 (0%) 1/10 (10%) 0/10 (0%) 2/16 (12.5%) 1/6 (16.7%)
    Amylase increased 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Aspartate aminotransferase increased 0/4 (0%) 2/10 (20%) 1/10 (10%) 4/16 (25%) 2/6 (33.3%)
    Blood alkaline phosphatase increased 0/4 (0%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Blood bilirubin increased 0/4 (0%) 1/10 (10%) 1/10 (10%) 1/16 (6.3%) 2/6 (33.3%)
    Blood calcium decreased 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Blood cholesterol increased 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Blood creatine phosphokinase MB increased 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Blood creatine phosphokinase increased 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Blood creatinine increased 3/4 (75%) 3/10 (30%) 2/10 (20%) 0/16 (0%) 2/6 (33.3%)
    Blood magnesium decreased 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 1/6 (16.7%)
    Blood phosphorus decreased 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Electrocardiogram QT prolonged 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 1/6 (16.7%)
    Gamma-glutamyltransferase increased 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Lipase increased 0/4 (0%) 1/10 (10%) 0/10 (0%) 2/16 (12.5%) 1/6 (16.7%)
    Neutrophil count decreased 1/4 (25%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Neutrophil count increased 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Platelet count decreased 0/4 (0%) 1/10 (10%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Weight decreased 2/4 (50%) 5/10 (50%) 9/10 (90%) 6/16 (37.5%) 2/6 (33.3%)
    Metabolism and nutrition disorders
    Decreased appetite 1/4 (25%) 5/10 (50%) 6/10 (60%) 8/16 (50%) 6/6 (100%)
    Dehydration 1/4 (25%) 5/10 (50%) 4/10 (40%) 4/16 (25%) 1/6 (16.7%)
    Glucose tolerance impaired 1/4 (25%) 2/10 (20%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Gout 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hypercalcaemia 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hyperglycaemia 1/4 (25%) 7/10 (70%) 9/10 (90%) 9/16 (56.3%) 4/6 (66.7%)
    Hyperkalaemia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hypoglycaemia 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Hypokalaemia 0/4 (0%) 3/10 (30%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Hypomagnesaemia 0/4 (0%) 2/10 (20%) 1/10 (10%) 1/16 (6.3%) 1/6 (16.7%)
    Hyponatraemia 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Metabolic acidosis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/4 (25%) 1/10 (10%) 0/10 (0%) 4/16 (25%) 0/6 (0%)
    Back pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 3/16 (18.8%) 1/6 (16.7%)
    Bone pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Flank pain 1/4 (25%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Muscle spasms 0/4 (0%) 0/10 (0%) 2/10 (20%) 4/16 (25%) 0/6 (0%)
    Muscular weakness 0/4 (0%) 1/10 (10%) 1/10 (10%) 1/16 (6.3%) 1/6 (16.7%)
    Musculoskeletal chest pain 0/4 (0%) 0/10 (0%) 1/10 (10%) 3/16 (18.8%) 0/6 (0%)
    Musculoskeletal discomfort 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Musculoskeletal pain 0/4 (0%) 0/10 (0%) 2/10 (20%) 2/16 (12.5%) 0/6 (0%)
    Myalgia 0/4 (0%) 2/10 (20%) 1/10 (10%) 3/16 (18.8%) 1/6 (16.7%)
    Myositis 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Neck pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Pain in extremity 0/4 (0%) 1/10 (10%) 0/10 (0%) 5/16 (31.3%) 0/6 (0%)
    Spinal pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Trismus 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Nervous system disorders
    Amnesia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Aphonia 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Balance disorder 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Disturbance in attention 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Dizziness 1/4 (25%) 3/10 (30%) 3/10 (30%) 2/16 (12.5%) 2/6 (33.3%)
    Dysarthria 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Dysgeusia 1/4 (25%) 4/10 (40%) 4/10 (40%) 3/16 (18.8%) 0/6 (0%)
    Headache 3/4 (75%) 1/10 (10%) 2/10 (20%) 5/16 (31.3%) 1/6 (16.7%)
    Hypoaesthesia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Memory impairment 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Paraesthesia 1/4 (25%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Presyncope 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 2/6 (33.3%)
    Somnolence 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 2/6 (33.3%)
    Transient ischaemic attack 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Psychiatric disorders
    Agitation 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Anxiety 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 1/6 (16.7%)
    Confusional state 0/4 (0%) 0/10 (0%) 1/10 (10%) 2/16 (12.5%) 1/6 (16.7%)
    Depression 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 1/6 (16.7%)
    Insomnia 0/4 (0%) 1/10 (10%) 4/10 (40%) 2/16 (12.5%) 0/6 (0%)
    Libido decreased 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Mental status changes 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Renal and urinary disorders
    Bladder spasm 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Cystitis noninfective 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Dysuria 0/4 (0%) 0/10 (0%) 1/10 (10%) 2/16 (12.5%) 0/6 (0%)
    Hydronephrosis 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Micturition urgency 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Neurogenic bladder 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Pollakiuria 0/4 (0%) 1/10 (10%) 2/10 (20%) 1/16 (6.3%) 0/6 (0%)
    Polyuria 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Renal failure acute 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Renal impairment 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Urinary retention 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 0/6 (0%)
    Urinary tract pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Reproductive system and breast disorders
    Breast pain 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pelvic pain 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Vulvovaginal dryness 0/4 (0%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Choking 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Cough 0/4 (0%) 2/10 (20%) 0/10 (0%) 6/16 (37.5%) 2/6 (33.3%)
    Dysphonia 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Dyspnoea 0/4 (0%) 4/10 (40%) 0/10 (0%) 4/16 (25%) 1/6 (16.7%)
    Dyspnoea exertional 0/4 (0%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Epistaxis 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hypoxia 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Laryngeal haemorrhage 1/4 (25%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Oropharyngeal pain 0/4 (0%) 2/10 (20%) 0/10 (0%) 2/16 (12.5%) 1/6 (16.7%)
    Paranasal sinus discomfort 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Paranasal sinus hypersecretion 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pleural effusion 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pneumothorax 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Productive cough 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Respiratory tract congestion 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Rhinitis allergic 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Rhinorrhoea 0/4 (0%) 0/10 (0%) 0/10 (0%) 3/16 (18.8%) 1/6 (16.7%)
    Sinus congestion 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Upper-airway cough syndrome 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Skin and subcutaneous tissue disorders
    Acanthosis nigricans 1/4 (25%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Alopecia 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 1/6 (16.7%)
    Blister 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Dermatitis 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Dermatitis acneiform 0/4 (0%) 0/10 (0%) 2/10 (20%) 0/16 (0%) 0/6 (0%)
    Dry skin 0/4 (0%) 1/10 (10%) 1/10 (10%) 1/16 (6.3%) 0/6 (0%)
    Erythema 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hyperhidrosis 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Ingrowing nail 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Nail disorder 0/4 (0%) 0/10 (0%) 1/10 (10%) 1/16 (6.3%) 0/6 (0%)
    Night sweats 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Onychoclasis 0/4 (0%) 0/10 (0%) 0/10 (0%) 0/16 (0%) 1/6 (16.7%)
    Prurigo 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Pruritus 0/4 (0%) 0/10 (0%) 2/10 (20%) 4/16 (25%) 1/6 (16.7%)
    Rash 0/4 (0%) 1/10 (10%) 0/10 (0%) 4/16 (25%) 0/6 (0%)
    Rash erythematous 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Rash macular 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Rash maculo-papular 2/4 (50%) 2/10 (20%) 2/10 (20%) 5/16 (31.3%) 0/6 (0%)
    Rash pruritic 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Skin discolouration 0/4 (0%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Urticaria 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)
    Vascular disorders
    Flushing 0/4 (0%) 0/10 (0%) 1/10 (10%) 0/16 (0%) 0/6 (0%)
    Hypertension 2/4 (50%) 0/10 (0%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Hypotension 0/4 (0%) 1/10 (10%) 0/10 (0%) 1/16 (6.3%) 0/6 (0%)
    Lymphoedema 0/4 (0%) 0/10 (0%) 0/10 (0%) 2/16 (12.5%) 0/6 (0%)
    Peripheral venous disease 0/4 (0%) 1/10 (10%) 0/10 (0%) 0/16 (0%) 0/6 (0%)

    Limitations/Caveats

    Due to the competitive landscape for anticancer therapies in ovarian and breast cancer and given the limited clinical activity observed with the study combination treatment, Novartis decided in 2014 to halt the recruitment in the trial.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 1-888-669-6682
    Email Novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01708161
    Other Study ID Numbers:
    • CBYL719X2105J
    • 2012-001962-13
    First Posted:
    Oct 16, 2012
    Last Update Posted:
    Sep 13, 2018
    Last Verified:
    Aug 1, 2018