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Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01525602
Collaborator
Plexxikon (Industry)
74
Enrollment
8
Locations
3
Arms
69.1
Duration (Months)
9.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was a 3-part study designed to explore the safety and tolerability of escalating doses of PLX3397 with weekly paclitaxel to establish a recommended Phase 2 dose (RP2D), to confirm RP2D in participants with advanced non-resectable solid tumors, and to determine the efficacy of PLX3397 600 mg twice daily (BID) administered in combination with weekly paclitaxel in participants with advanced, metastatic or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
74 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Study to Assess the Safety of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors
Study Start Date :
May 1, 2012
Actual Primary Completion Date :
Dec 1, 2017
Actual Study Completion Date :
Feb 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1

Open-label, sequential PLX3397 single-agent dose escalation in combination with paclitaxel in approximately 30 patients with advanced solid tumors. Enrollment completed. (Closed to recruitment)

Drug: PLX3397
PLX3397 tablets, 200mg
Other Names:
  • Pexidartinib

    • Drug: Paclitaxel
    Paclitaxel IV
    Other Names:
  • Onxol

    		•
    Experimental: Part 2

    Extension cohort at the RP2D of single-agent PLX3397 in combination with paclitaxel in approximately 30 patients in advanced solid tumors. Enrollment completed. (Closed to recruitment)

    Drug: PLX3397
    PLX3397 tablets, 200mg
    Other Names:
  • Pexidartinib

    • Drug: Paclitaxel
    Paclitaxel IV
    Other Names:
  • Onxol

    		•
    Experimental: Part 3

    Extension cohort at the RP2D of single-agent PLX3397 in combination with paclitaxel in approximately 30 patients with advanced, metastatic, or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. (Closed to recruitment)

    Drug: PLX3397
    PLX3397 tablets, 200mg
    Other Names:
  • Pexidartinib

    • Drug: Paclitaxel
    Paclitaxel IV
    Other Names:
  • Onxol

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Treatment-emergent Adverse Events (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Safety Population) [From post first dose up to 28 days after the last dose, up to 5 years 9 months]

      Treatment-emergent adverse events (TEAEs) reported by >10% of all participants in Parts 1 and 2 are reported.

    2. Percentage of Participants With TEAEs (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Safety Population) [From post first dose up to 28 days after the last dose, up to 5 years 9 months]

      Treatment-emergent adverse events (TEAEs) reported by >10% of all participants in Part 3 are reported.

    3. Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population) [From post first dose up to 5 years 9 months post dose]

      Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    4. Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population) [From 26 days (CR and PR) and 54 days (SD) up to 5 years 9 months post dose]

      Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Secondary Outcome Measures

    1. Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population) [From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose]

    2. Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population) [From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose]

    3. Progression-free Survival Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population) [From the first day of treatment to the first documented disease progression or date of death, whichever occurred first, up to 5 years 9 months post dose]

      Progression-free survival (PFS) is defined as the number of days from the start of therapy (i.e. Cycle 1 Day 1) to the date of first documented disease progression/relapse or death, whichever occurs first. If the disease progression/relapse does not occur, PFS will be censored as of the date of their last evaluable tumor assessments.

    4. A Summary of Pharmacokinetic Parameter (Tmax) Following Exposure to PLX3397 (Parts 1 and 3) [Cycle 1, Day 15]

    5. A Summary of Pharmacokinetic Parameter (Cmax) Following Exposure to PLX3397 (Parts 1 and 3) [Cycle 1, Day 15]

    6. A Summary of Pharmacokinetic Parameters (AUC[0-4h], AUC[0-6h], and AUC[0-12h]) Following Exposure to PLX3397 (Parts 1 and 3) [Cycle 1, Day 15]

    7. Percentage of Participants With PLX3397-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set) [From post first dose up to 28 days after the last dose, up to 5 years 9 months]

    8. Percentage of Participants With Paclitaxel-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set) [From post first dose up to 28 days after the last dose, up to 5 years 9 months]

    9. Percentage of Participants With PLX3397- and/or Paclitaxel-Related TEAEs (>10%) by Preferred Term (Part 3) (Safety Analysis Set) [From post first dose up to 28 days after the last dose, up to 5 years 9 months]

    Eligibility Criteria

    Criteria

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

    • Patients with:

    • Part 1 (enrollment closed): an advanced, incurable solid tumor

    • Part 2 (enrollment closed): an advanced, incurable solid tumor for whom a taxane would be considered a reasonable chemotherapy option

    • Part 3 (enrollment closed): advanced, metastatic or non-resectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer with

    • platinum-resistant cancer, defined as disease that responded to a platinum-containing chemotherapy regimen, but demonstrated recurrence within six months following the completion of that platinum-containing regimen, OR

    • platinum-refractory cancer, defined as disease failed to achieve at least a partial response to a platinum-containing regimen (i.e., stable disease or actual disease progression), AND

    • have not been treated with a taxane within six months of Cycle 1 Day 1 (C1D1), AND

    • have not been treated with weekly paclitaxel after first-line treatment in which weekly paclitaxel plus a platinum is permitted

    • Part 3: Patients must have target (≥2 cm diameter) or non-target lesion cancer that is accessible for core biopsies before starting on study and after one cycle of treatment.

    • Patients with stable brain metastases are eligible for this trial. However, patients must not have required steroid treatment for their brain metastases within 30 days of Screening.

    • Bone-directed therapy (e.g., bisphosphonates or denosumab) is permitted.

    • Washout from any prior investigational therapy of at least five times the T1/2 prior to C1D1

    • Washout from any prior biologic or targeted therapy at least 4 weeks or five times the plasma half-life (T1/2) (whichever is shorter) prior to C1D1

    • Washout from prior chemotherapy of at least 2 weeks or 1 elimination half-life, whichever is longer, prior to C1D1

    • Washout from prior hormonal therapy of at least 2 weeks prior to C1D1

    • Washout of at least 2 weeks from the most recent radiation treatment prior to C1D1

    • Resolution of all prior treatment-related toxicities to Grade 1 or less, except for Grade 2 fatigue or alopecia prior to C1D1

    • Age eighteen years or older

    • Eastern Cooperative Oncology Group (ECOG) performance status 0-2, inclusive

    • Anticipated life expectancy of at least 12 weeks

    • Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥1500/mm3, platelets ≥100,000/mm3

    • Adequate renal function: serum creatinine <1.5 x ULN or calculated creatinine clearance (CrCl) >60 mL/min using Cockcroft-Gault formula

    • Adequate hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x upper limit of normal (ULN), Total and Direct Bilirubin <1.5 x ULN. However, in the presence of liver metastases, AST and ALT must be <5 x ULN

    • Cardiac ejection fraction ≥50%, and QT interval corrected by Fridericia's formula (QTcF) <450 ms (males) or <470 ms (females) on electrocardiogram (ECG) at Baseline.

    • Able to swallow capsules and maintain adequate hydration

    • Ability to give written informed consent and willing to comply with the requirements of the protocol; and for Part 3, to give written informed consent for 2 cancer biopsy procedures

    • Women of child-bearing potential must agree to use an effective method of birth control during treatment and for three months after receiving their last dose of study drug. Fertile men must also agree to use an acceptable method of birth control while on study drug and for at least 3 months after last dose.

    Exclusion Criteria:

    • Presence of an active secondary malignancy.

    • Patients with a non-melanomatous, in situ malignancy or disease that is completely resectable with surgery may be considered after discussion with the Medical Monitor

    • Patients with a completely treated prior malignancy with no evidence of disease for ≥3 years are eligible

    • Refractory nausea and vomiting, malabsorption, external biliary shunt or significant small bowel resection that would preclude adequate absorption of PLX3397

    • Ongoing treatment with any other investigational therapy

    • Prior anaphylactic or severe hypersensitivity reaction to paclitaxel or Cremophor-containing agent.

    • Persistent grade 2 fatigue at Baseline.

    • Severe, concurrent illness including congestive heart failure, significant cardiac disease and uncontrolled hypertension, that would likely prevent the patient from being able to comply with the study protocol

    • Active untreated infection

    • Known chronic active Hepatitis B or C, or HIV infection

    • The presence of a medical or psychiatric condition that, in the opinion of the Principal Investigator, makes the patient inappropriate for inclusion in this study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35233
    2 Univeristy of California, San Francisco San Francisco California United States 94143
    3 University of Colorado, Anschutz Cancer Pavilion Aurora Colorado United States 80045
    4 Sylvester Comprehensive Cancer Center/UMHC Miami Florida United States 33136
    5 Mayo Clinic Rochester Minnesota United States 55905
    6 University Hospitals of Cleveland Cleveland Ohio United States 44106
    7 Ohio State University Columbus Ohio United States 43210
    8 University of Utah, Huntsman Cancer Institute Salt Lake City Utah United States 84112

    Sponsors and Collaborators

    • Daiichi Sankyo, Inc.
    • Plexxikon

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Daiichi Sankyo, Inc.
    ClinicalTrials.gov Identifier:
    NCT01525602
    Other Study ID Numbers:
    • PLX108-07
    First Posted:
    Feb 3, 2012
    Last Update Posted:
    Jul 16, 2020
    Last Verified:
    Jul 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Daiichi Sankyo, Inc.
    advanced, incurable solid tumors
    Additional relevant MeSH terms:
    Neoplasms
    Paclitaxel

    Study Results

    Participant Flow

    Recruitment Details A total of 74 participants (54 in Parts 1 and 2; 20 in Part 3) who met all inclusion and none of the exclusion criteria were enrolled in this study.
    Pre-assignment Detail An open-label study. In Part 1 (dose escalation), participants were sequentially enrolled and received doses of PLX3397 600 to 1600 mg/day. In Part 2 (dose expansion), PLX3397 was administered at the recommended phase 2 dose with paclitaxel. In Part 3, PLX3397 was administered at 600 mg twice daily with paclitaxel; 2 participants were not dosed.
    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg + Paclitaxel 80 mg/m^2
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day. All participants with advanced solid tumors who received PLX3397 600 mg twice daily (BID) as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg twice daily (BID) and paclitaxel 80 mg/m^2 IV weekly. All participants who received PLX3397 600 mg twice daily (BID) + paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment.
    Period Title: Overall Study
    STARTED 9 3 3 6 33 7 6 7
    COMPLETED 0 0 0 0 0 0 0 0
    NOT COMPLETED 9 3 3 6 33 7 6 7

    Baseline Characteristics

    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg + Paclitaxel 80 mg/m^2 Total
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day. All participants with advanced solid tumors who received PLX3397 600 mg BID as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. Total of all reporting groups
    Overall Participants 9 3 3 6 33 7 5 6 72
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.4
    (14.2)
    55.0
    (5.3)
    60.3
    (11.1)
    58.7
    (16.4)
    58.9
    (10.7)
    64.0
    (10.4)
    64.8
    (4.9)
    59.7
    (8.8)
    59.5
    (10.9)
    Sex: Female, Male (Count of Participants)
    Female
    6
    66.7%
    3
    100%
    1
    33.3%
    3
    50%
    20
    60.6%
    7
    100%
    5
    100%
    6
    100%
    51
    70.8%
    Male
    3
    33.3%
    0
    0%
    2
    66.7%
    3
    50%
    13
    39.4%
    0
    0%
    0
    0%
    0
    0%
    21
    29.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3%
    0
    0%
    0
    0%
    1
    16.7%
    2
    2.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    33.3%
    0
    0%
    1
    16.7%
    2
    6.1%
    0
    0%
    0
    0%
    0
    0%
    4
    5.6%
    White
    9
    100%
    2
    66.7%
    3
    100%
    5
    83.3%
    29
    87.9%
    7
    100%
    5
    100%
    5
    83.3%
    65
    90.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3%
    0
    0%
    0
    0%
    0
    0%
    1
    1.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    9
    100%
    3
    100%
    3
    100%
    6
    100%
    33
    100%
    7
    100%
    5
    100%
    6
    100%
    72
    100%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Treatment-emergent Adverse Events (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Safety Population)
    Description Treatment-emergent adverse events (TEAEs) reported by >10% of all participants in Parts 1 and 2 are reported.
    Time Frame From post first dose up to 28 days after the last dose, up to 5 years 9 months

    Outcome Measure Data

    Analysis Population Description
    Safety events were assessed in the Safety Population.
    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day.
    Measure Participants 9 3 3 6 33
    Any TEAE
    100
    1111.1%
    100
    3333.3%
    100
    3333.3%
    100
    1666.7%
    100
    303%
    Gastrointestinal disorders
    89
    988.9%
    67
    2233.3%
    100
    3333.3%
    83
    1383.3%
    91
    275.8%
    Nausea
    44
    488.9%
    33
    1100%
    67
    2233.3%
    67
    1116.7%
    42
    127.3%
    Diarrhea
    33
    366.7%
    33
    1100%
    67
    2233.3%
    50
    833.3%
    39
    118.2%
    Vomiting
    33
    366.7%
    0
    0%
    33
    1100%
    33
    550%
    36
    109.1%
    Constipation
    33
    366.7%
    0
    0%
    33
    1100%
    0
    0%
    21
    63.6%
    General disorders/administrative site conditions
    89
    988.9%
    100
    3333.3%
    67
    2233.3%
    100
    1666.7%
    79
    239.4%
    Fatigue
    78
    866.7%
    100
    3333.3%
    33
    1100%
    83
    1383.3%
    70
    212.1%
    Edema peripheral
    11
    122.2%
    33
    1100%
    0
    0%
    33
    550%
    27
    81.8%
    Pyrexia
    22
    244.4%
    0
    0%
    33
    1100%
    17
    283.3%
    18
    54.5%
    Blood and lymphatic disorders
    89
    988.9%
    100
    3333.3%
    67
    2233.3%
    50
    833.3%
    73
    221.2%
    Anemia
    78
    866.7%
    67
    2233.3%
    33
    1100%
    33
    550%
    67
    203%
    Neutropenia
    22
    244.4%
    33
    1100%
    33
    1100%
    33
    550%
    12
    36.4%
    Metabolism and nutrition disorders
    78
    866.7%
    67
    2233.3%
    33
    1100%
    83
    1383.3%
    67
    203%
    Decreased appetite
    78
    866.7%
    33
    1100%
    0
    0%
    67
    1116.7%
    36
    109.1%
    Hypokalemia
    22
    244.4%
    33
    1100%
    0
    0%
    33
    550%
    27
    81.8%
    Hypophosphatemia
    11
    122.2%
    33
    1100%
    0
    0%
    17
    283.3%
    24
    72.7%
    Skin and subcutaneous disorders
    56
    622.2%
    100
    3333.3%
    100
    3333.3%
    100
    1666.7%
    55
    166.7%
    Alopecia
    11
    122.2%
    33
    1100%
    33
    1100%
    67
    1116.7%
    24
    72.7%
    Rash
    11
    122.2%
    33
    1100%
    33
    1100%
    0
    0%
    27
    81.8%
    Pruritus
    0
    0%
    33
    1100%
    0
    0%
    17
    283.3%
    15
    45.5%
    Respiratory, thoracic, and mediastinal disorders
    33
    366.7%
    67
    2233.3%
    100
    3333.3%
    50
    833.3%
    61
    184.8%
    Dyspnea
    22
    244.4%
    33
    1100%
    0
    0%
    50
    833.3%
    33
    100%
    Cough
    11
    122.2%
    0
    0%
    0
    0%
    33
    550%
    18
    54.5%
    Investigations
    11
    122.2%
    67
    2233.3%
    100
    3333.3%
    67
    1116.7%
    61
    184.8%
    Aspartate aminotransferase increased
    0
    0%
    67
    2233.3%
    33
    1100%
    33
    550%
    42
    127.3%
    Lymphocyte count decreased
    11
    122.2%
    67
    2233.3%
    33
    1100%
    33
    550%
    36
    109.1%
    White blood cell count decreased
    0
    0%
    67
    2233.3%
    33
    1100%
    50
    833.3%
    36
    109.1%
    Blood creatinine phosphokinase increased
    0
    0%
    33
    1100%
    67
    2233.3%
    17
    283.3%
    39
    118.2%
    Neutrohil count decreased
    0
    0%
    33
    1100%
    0
    0%
    17
    283.3%
    36
    109.1%
    Alanine aminotransferase increased
    0
    0%
    33
    1100%
    33
    1100%
    17
    283.3%
    21
    63.6%
    Blood alkaline phosphatase increased
    0
    0%
    33
    1100%
    33
    1100%
    17
    283.3%
    21
    63.6%
    Respiratory rate increased
    0
    0%
    0
    0%
    33
    1100%
    17
    283.3%
    12
    36.4%
    Weight decreased
    11
    122.2%
    33
    1100%
    33
    1100%
    17
    283.3%
    6
    18.2%
    Nervous system disorders
    44
    488.9%
    67
    2233.3%
    67
    2233.3%
    67
    1116.7%
    55
    166.7%
    Dysgeusia
    11
    122.2%
    0
    0%
    33
    1100%
    50
    833.3%
    36
    109.1%
    Dizziness
    33
    366.7%
    0
    0%
    0
    0%
    17
    283.3%
    12
    36.4%
    Neuropathy peripheral
    22
    244.4%
    0
    0%
    33
    1100%
    17
    283.3%
    12
    36.4%
    Headache
    0
    0%
    33
    1100%
    0
    0%
    17
    283.3%
    12
    36.4%
    Vascular disorders
    11
    122.2%
    67
    2233.3%
    0
    0%
    50
    833.3%
    39
    118.2%
    Hypertension
    11
    122.2%
    67
    2233.3%
    0
    0%
    50
    833.3%
    30
    90.9%
    Eye disorders
    11
    122.2%
    67
    2233.3%
    33
    1100%
    33
    550%
    30
    90.9%
    Periorbital edema
    0
    0%
    33
    1100%
    33
    1100%
    0
    0%
    15
    45.5%
    Vision blurred
    0
    0%
    0
    0%
    0
    0%
    17
    283.3%
    15
    45.5%
    Psychiatric disorders
    11
    122.2%
    0
    0%
    0
    0%
    17
    283.3%
    21
    63.6%
    Insomnia
    11
    122.2%
    0
    0%
    0
    0%
    0
    0%
    15
    45.5%
    2. Primary Outcome
    Title Percentage of Participants With TEAEs (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Safety Population)
    Description Treatment-emergent adverse events (TEAEs) reported by >10% of all participants in Part 3 are reported.
    Time Frame From post first dose up to 28 days after the last dose, up to 5 years 9 months

    Outcome Measure Data

    Analysis Population Description
    Safety events were assessed in the Safety Population.
    Arm/Group Title Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg + Paclitaxel 80 mg/m^2
    Arm/Group Description All participants with advanced solid tumors who received PLX3397 600 mg BID as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment.
    Measure Participants 7 5 6
    Any TEAE
    100
    1111.1%
    100
    3333.3%
    100
    3333.3%
    Gastrointestinal disorders
    100
    1111.1%
    100
    3333.3%
    83.3
    2776.7%
    Nausea
    71.4
    793.3%
    60
    2000%
    66.7
    2223.3%
    Diarrhea
    57.1
    634.4%
    40
    1333.3%
    50
    1666.7%
    Constipation
    28.6
    317.8%
    60
    2000%
    16.7
    556.7%
    Vomiting
    14.3
    158.9%
    40
    1333.3%
    50
    1666.7%
    Abdominal distension
    14.3
    158.9%
    40
    1333.3%
    16.7
    556.7%
    Abdominal pain
    28.6
    317.8%
    20
    666.7%
    16.7
    556.7%
    Stomatitis
    0
    0%
    40
    1333.3%
    16.7
    556.7%
    Colitis
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Toothache
    14.3
    158.9%
    20
    666.7%
    0
    0%
    General disorders/administrative site conditions
    42.9
    476.7%
    100
    3333.3%
    100
    3333.3%
    Fatigue
    42.9
    476.7%
    80
    2666.7%
    100
    3333.3%
    Chills
    0
    0%
    0
    0%
    66.7
    2223.3%
    Edema peripheral
    14.3
    158.9%
    40
    1333.3%
    0
    0%
    Pyrexia
    0
    0%
    0
    0%
    50
    1666.7%
    Chest pain
    14.3
    158.9%
    20
    666.7%
    0
    0%
    Face edema
    0
    0%
    20
    666.7%
    16.7
    556.7%
    Nervous system disorders
    57.1
    634.4%
    100
    3333.3%
    66.7
    2223.3%
    Dysgeusia
    42.9
    476.7%
    40
    1333.3%
    33.3
    1110%
    Neuropathy peripheral
    28.6
    317.8%
    60
    2000%
    16.7
    556.7%
    Dizziness
    28.6
    317.8%
    20
    666.7%
    33.3
    1110%
    Headache
    14.3
    158.9%
    20
    666.7%
    16.7
    556.7%
    Skin and subcutaneous tissue disorders
    57.1
    634.4%
    80
    2666.7%
    50
    1666.7%
    Alopecia
    42.9
    476.7%
    80
    2666.7%
    16.7
    556.7%
    Pruritus
    14.3
    158.9%
    20
    666.7%
    16.7
    556.7%
    Rash
    0
    0%
    40
    1333.3%
    0
    0%
    Respiratory, thoracic, and mediastinal disorders
    28.6
    317.8%
    80
    2666.7%
    66.7
    2223.3%
    Dyspnea
    28.6
    317.8%
    40
    1333.3%
    33.3
    1110%
    Epistaxis
    14.3
    158.9%
    40
    1333.3%
    16.7
    556.7%
    Cough
    14.3
    158.9%
    40
    1333.3%
    0
    0%
    Oropharyngeal pain
    14.3
    158.9%
    20
    666.7%
    0
    0%
    Musculoskeletal and connective tissue disorders
    28.6
    317.8%
    60
    2000%
    66.7
    2223.3%
    Pain in extremity
    14.3
    158.9%
    20
    666.7%
    33.3
    1110%
    Myalgia
    0
    0%
    0
    0%
    33.3
    1110%
    Investigations
    42.9
    476.7%
    20
    666.7%
    66.7
    2223.3%
    Alanine aminotransferase increased
    14.3
    158.9%
    20
    666.7%
    16.7
    556.7%
    Aspartate aminotransferase increased
    14.3
    158.9%
    20
    666.7%
    16.7
    556.7%
    Blood bilirubin increased
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Lymphocyte count decreased
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Neutrophil count decreased
    0
    0%
    0
    0%
    33.3
    1110%
    Metabolism and nutrition disorders
    42.9
    476.7%
    60
    2000%
    33.3
    1110%
    Decreased appetite
    42.9
    476.7%
    60
    2000%
    16.7
    556.7%
    Blood and lymphatic system disorders
    28.6
    317.8%
    40
    1333.3%
    50
    1666.7%
    Anemia
    28.6
    317.8%
    20
    666.7%
    33.3
    1110%
    Neutropenia
    0
    0%
    20
    666.7%
    16.7
    556.7%
    Infections and infestations
    28.6
    317.8%
    20
    666.7%
    50
    1666.7%
    Pneumonia
    28.6
    317.8%
    20
    666.7%
    0
    0%
    Renal and urinary disorders
    28.6
    317.8%
    0
    0%
    50
    1666.7%
    Dysuria
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Urinary incontinence
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Vascular disorders
    0
    0%
    20
    666.7%
    50
    1666.7%
    Hypertension
    0
    0%
    0
    0%
    50
    1666.7%
    Injury, poisoning, and procedural complications
    14.3
    158.9%
    0
    0%
    33.3
    1110%
    Contusion
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Reproductive system and breast disorders
    28.6
    317.8%
    20
    666.7%
    0
    0%
    Vaginal hemorrhage
    14.3
    158.9%
    20
    666.7%
    0
    0%
    3. Primary Outcome
    Title Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population)
    Description Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
    Time Frame From post first dose up to 5 years 9 months post dose

    Outcome Measure Data

    Analysis Population Description
    Best overall tumor response was assessed in the Efficacy Evaluable Population.
    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day.
    Measure Participants 6 3 3 6 20
    Complete response (CR)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    15.2%
    Partial response (PR)
    17
    188.9%
    0
    0%
    33
    1100%
    17
    283.3%
    10
    30.3%
    Stable disease
    33
    366.7%
    33
    1100%
    33
    1100%
    50
    833.3%
    30
    90.9%
    Progressive disease
    50
    555.6%
    67
    2233.3%
    33
    1100%
    33
    550%
    45
    136.4%
    Unable to assess
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    10
    30.3%
    Best overall response rate (CR or PR)
    17
    188.9%
    0
    0%
    33
    1100%
    17
    283.3%
    15
    45.5%
    Clinical benefit rate (CR, PR, or stable disease)
    50
    555.6%
    33
    1100%
    67
    2233.3%
    67
    1116.7%
    45
    136.4%
    4. Primary Outcome
    Title Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)
    Description Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
    Time Frame From 26 days (CR and PR) and 54 days (SD) up to 5 years 9 months post dose

    Outcome Measure Data

    Analysis Population Description
    Best overall tumor response was assessed in the Efficacy Evaluable Population.
    Arm/Group Title Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Arm/Group Description All participants with advanced solid tumors who received PLX3397 600 mg BID as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment.
    Measure Participants 4 5 5
    Complete response (CR)
    0
    0%
    0
    0%
    0
    0%
    Partial response (PR)
    0
    0%
    40
    1333.3%
    20
    666.7%
    Stable disease (SD)
    50
    555.6%
    0
    0%
    20
    666.7%
    Progressive disease (PD)
    50
    555.6%
    60
    2000%
    60
    2000%
    Best overall response rate (CR or PR)
    0
    0%
    40
    1333.3%
    20
    666.7%
    Clinical benefit rate (CR, PR, or stable disease)
    50
    555.6%
    40
    1333.3%
    40
    1333.3%
    5. Secondary Outcome
    Title Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population)
    Description
    Time Frame From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose

    Outcome Measure Data

    Analysis Population Description
    Duration of response was assessed in the Efficacy Evaluable Population.
    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day.
    Measure Participants 1 0 1 1 3
    Mean (Standard Deviation) [days]
    171
    (0)
    9
    (0)
    66
    (0)
    113.3
    (68.8)
    6. Secondary Outcome
    Title Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)
    Description
    Time Frame From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose

    Outcome Measure Data

    Analysis Population Description
    Duration of response based on patients with CR or PR was assessed in the Efficacy Evaluable Population.
    Arm/Group Title Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Arm/Group Description All participants with advanced solid tumors who received PLX3397 600 mg BID as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment.
    Measure Participants 0 2 1
    Median (95% Confidence Interval) [days]
    119
    114
    7. Secondary Outcome
    Title Progression-free Survival Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population)
    Description Progression-free survival (PFS) is defined as the number of days from the start of therapy (i.e. Cycle 1 Day 1) to the date of first documented disease progression/relapse or death, whichever occurs first. If the disease progression/relapse does not occur, PFS will be censored as of the date of their last evaluable tumor assessments.
    Time Frame From the first day of treatment to the first documented disease progression or date of death, whichever occurred first, up to 5 years 9 months post dose

    Outcome Measure Data

    Analysis Population Description
    Progression-free survival was assessed in the Efficacy Evaluable Population.
    Arm/Group Title Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Arm/Group Description All participants with advanced solid tumors who received PLX3397 600 mg BID as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment.
    Measure Participants 4 5 5
    Median (95% Confidence Interval) [days]
    117
    59
    56
    8. Secondary Outcome
    Title A Summary of Pharmacokinetic Parameter (Tmax) Following Exposure to PLX3397 (Parts 1 and 3)
    Description
    Time Frame Cycle 1, Day 15

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
    Arm/Group Title Part 1: 600 mg BID Part 1: 800 mg (400 mg BID) Part 1: 1000 mg (BID) Part 1: 1200 mg (600 mg BID) Part 1 and 2: 1600 mg (800 mg BID) Part 3: 1200 mg (600 mg BID)
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg BID administered as three 100-mg capsules in the morning and evening, or two 200-mg capsules in the morning and one 200-mg capsule in the evening. Participants with advanced solid tumors who received PLX3397 800 mg administered 400 mg BID. Participants with advanced solid tumors who received PLX3397 1000 mg BID administered as five 100-mg capsules in the morning and evening, or three 200-mg capsules in the morning and two 200-mg capsules in the evening. Participants with advanced solid tumors who received PLX3397 1200 mg administered 600 mg BID. Participants with advanced solid tumors who received PLX3397 1600 mg administered 800 mg BID. Participants with advanced solid tumors who received PLX3397 1200 mg administered 600 mg BID.
    Measure Participants 6 3 3 6 6 6
    Median (Full Range) [hours]
    0
    2
    0
    2
    2
    2
    9. Secondary Outcome
    Title A Summary of Pharmacokinetic Parameter (Cmax) Following Exposure to PLX3397 (Parts 1 and 3)
    Description
    Time Frame Cycle 1, Day 15

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
    Arm/Group Title Part 1: 600 mg BID Part 1: 800 mg (400 mg BID) Part 1: 1000 mg (BID) Part 1: 1200 mg (600 mg BID) Part 1 and 2: 1600 mg (800 mg BID) Part 3: 1200 mg (600 mg BID)
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg BID administered as three 100-mg capsules in the morning and evening, or two 200-mg capsules in the morning and one 200-mg capsule in the evening. Participants with advanced solid tumors who received PLX3397 800 mg administered 400 mg BID. Participants with advanced solid tumors who received PLX3397 1000 mg BID administered as five 100-mg capsules in the morning and evening, or three 200-mg capsules in the morning and two 200-mg capsules in the evening. Participants with advanced solid tumors who received PLX3397 1200 mg administered 600 mg BID. Participants with advanced solid tumors who received PLX3397 1600 mg administered 800 mg BID. Participants with advanced solid tumors who received PLX3397 1200 mg administered 600 mg BID.
    Measure Participants 6 3 3 6 6 6
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    3420
    (41.4)
    6640
    (26.5)
    4340
    (27.6)
    8190
    (39.6)
    8000
    (50.5)
    8540
    (17.8)
    10. Secondary Outcome
    Title A Summary of Pharmacokinetic Parameters (AUC[0-4h], AUC[0-6h], and AUC[0-12h]) Following Exposure to PLX3397 (Parts 1 and 3)
    Description
    Time Frame Cycle 1, Day 15

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set, except for AUC(0-6) which was not performed for Part 1 and 2 participants, only participants in Part 3.
    Arm/Group Title Part 1: 600 mg BID Part 1: 800 mg (400 mg BID) Part 1: 1000 mg (BID) Part 1: 1200 mg (600 mg BID) Part 1 and 2: 1600 mg (800 mg BID) Part 3: 1200 mg (600 mg BID)
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg BID administered as three 100-mg capsules in the morning and evening, or two 200-mg capsules in the morning and one 200-mg capsule in the evening. Participants with advanced solid tumors who received PLX3397 800 mg administered 400 mg BID. Participants with advanced solid tumors who received PLX3397 1000 mg BID administered as five 100-mg capsules in the morning and evening, or three 200-mg capsules in the morning and two 200-mg capsules in the evening. Participants with advanced solid tumors who received PLX3397 1200 mg administered 600 mg BID. Participants with advanced solid tumors who received PLX3397 1600 mg administered 800 mg BID. Participants with advanced solid tumors who received PLX3397 1200 mg administered 600 mg BID.
    Measure Participants 6 3 3 6 6 6
    AUC (0-4)
    12400
    (41.0)
    21700
    (25.7)
    13100
    (38.6)
    28000
    (34.5)
    26500
    (46.5)
    27800
    (17.5)
    AUC (0-6)
    40100
    (19.4)
    AUC (0-12)
    36900
    (37.1)
    59300
    (16.0)
    44400
    (30.7)
    75600
    (34.2)
    70500
    (36.7)
    71700
    (21.2)
    11. Secondary Outcome
    Title Percentage of Participants With PLX3397-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set)
    Description
    Time Frame From post first dose up to 28 days after the last dose, up to 5 years 9 months

    Outcome Measure Data

    Analysis Population Description
    Safety events were assessed in the Safety Analysis Set.
    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day.
    Measure Participants 9 3 3 6 33
    Any Paclitaxel-related TEAE
    89
    988.9%
    100
    3333.3%
    100
    3333.3%
    100
    1666.7%
    94
    284.8%
    Nausea
    22
    244.4%
    33
    1100%
    33
    1100%
    50
    833.3%
    36
    109.1%
    Diarrhea
    22
    244.4%
    33
    1100%
    67
    2233.3%
    50
    833.3%
    24
    72.7%
    Vomiting
    22
    244.4%
    0
    0%
    33
    1100%
    33
    550%
    27
    81.8%
    Fatigue
    33
    366.7%
    100
    3333.3%
    33
    1100%
    83
    1383.3%
    64
    193.9%
    Pyrexia
    11
    122.2%
    0
    0%
    33
    1100%
    0
    0%
    12
    36.4%
    Anemia
    33
    366.7%
    67
    2233.3%
    0
    0%
    17
    283.3%
    36
    109.1%
    Decreased appetite
    33
    366.7%
    33
    1100%
    0
    0%
    66
    1100%
    24
    72.7%
    Hypophosphatemia
    11
    122.2%
    33
    1100%
    0
    0%
    17
    283.3%
    15
    45.5%
    Rash
    11
    122.2%
    0
    0%
    33
    1100%
    0
    0%
    27
    81.8%
    Pruritus
    0
    0%
    33
    1100%
    0
    0%
    17
    283.3%
    15
    45.5%
    Aspartate aminotransferase increased
    0
    0%
    67
    2233.3%
    33
    1100%
    33
    550%
    42
    127.3%
    White blood cell count decreased
    0
    0%
    33
    1100%
    33
    1100%
    50
    833.3%
    33
    100%
    Blood creatinine phosphokinase increased
    0
    0%
    33
    1100%
    67
    2233.3%
    17
    283.3%
    39
    118.2%
    Neutrophil count decreased
    0
    0%
    33
    1100%
    0
    0%
    17
    283.3%
    21
    63.6%
    Alanine aminotransferase increased
    0
    0%
    33
    1100%
    33
    1100%
    17
    283.3%
    21
    63.6%
    Blood alkaline phosphatase increased
    0
    0%
    33
    1100%
    33
    1100%
    17
    283.3%
    18
    54.5%
    Dysgeusia
    0
    0%
    0
    0%
    33
    1100%
    67
    1116.7%
    30
    90.9%
    Hypertension
    11
    122.2%
    67
    2233.3%
    0
    0%
    50
    833.3%
    21
    63.6%
    Periorbital edema
    0
    0%
    33
    1100%
    33
    1100%
    0
    0%
    15
    45.5%
    12. Secondary Outcome
    Title Percentage of Participants With Paclitaxel-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set)
    Description
    Time Frame From post first dose up to 28 days after the last dose, up to 5 years 9 months

    Outcome Measure Data

    Analysis Population Description
    Safety events were assessed in the Safety Analysis Set.
    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day.
    Measure Participants 9 3 3 6 33
    Any Paclitaxel-related TEAE
    89
    988.9%
    100
    3333.3%
    100
    3333.3%
    100
    1666.7%
    94
    284.8%
    Nausea
    33
    366.7%
    33
    1100%
    33
    1100%
    50
    833.3%
    27
    81.8%
    Diarrhea
    33
    366.7%
    33
    1100%
    67
    2233.3%
    50
    833.3%
    33
    100%
    Vomiting
    22
    244.4%
    0
    0%
    33
    1100%
    33
    550%
    24
    72.7%
    Fatigue
    67
    744.4%
    100
    3333.3%
    33
    1100%
    83
    1383.3%
    52
    157.6%
    Edema peripheral
    0
    0%
    0
    0%
    0
    0%
    17
    283.3%
    15
    45.5%
    Pyrexia
    11
    122.2%
    0
    0%
    33
    1100%
    0
    0%
    15
    45.5%
    Anemia
    67
    744.4%
    67
    2233.3%
    33
    1100%
    33
    550%
    64
    193.9%
    Neutropenia
    22
    244.4%
    33
    1100%
    33
    1100%
    33
    550%
    12
    36.4%
    Decreased appetite
    44
    488.9%
    33
    1100%
    0
    0%
    67
    1116.7%
    24
    72.7%
    Hypophosphatemia
    11
    122.2%
    33
    1100%
    0
    0%
    0
    0%
    12
    36.4%
    Alopecia
    11
    122.2%
    33
    1100%
    33
    1100%
    67
    1116.7%
    24
    72.7%
    Rash
    11
    122.2%
    0
    0%
    0
    0%
    0
    0%
    24
    72.7%
    Pruritus
    0
    0%
    33
    1100%
    0
    0%
    17
    283.3%
    12
    36.4%
    Aspartate aminotransferase increased
    0
    0%
    67
    2233.3%
    33
    1100%
    33
    550%
    42
    127.3%
    Lymphocyte count decreased
    11
    122.2%
    0
    0%
    0
    0%
    33
    550%
    36
    109.1%
    White blood cell count decreased
    0
    0%
    67
    2233.3%
    33
    1100%
    50
    833.3%
    33
    100%
    Blood creatinine phosphokinase increased
    0
    0%
    33
    1100%
    67
    2233.3%
    17
    283.3%
    6
    18.2%
    Neutrophil count decreased
    0
    0%
    33
    1100%
    0
    0%
    17
    283.3%
    36
    109.1%
    Alanine aminotransferase increased
    0
    0%
    33
    1100%
    33
    1100%
    17
    283.3%
    21
    63.6%
    Blood alkaline phosphatase increased
    0
    0%
    33
    1100%
    33
    1100%
    17
    283.3%
    12
    36.4%
    Dysgeusia
    11
    122.2%
    0
    0%
    33
    1100%
    50
    833.3%
    30
    90.9%
    Neuropathy peripheral
    22
    244.4%
    0
    0%
    33
    1100%
    17
    283.3%
    12
    36.4%
    13. Secondary Outcome
    Title Percentage of Participants With PLX3397- and/or Paclitaxel-Related TEAEs (>10%) by Preferred Term (Part 3) (Safety Analysis Set)
    Description
    Time Frame From post first dose up to 28 days after the last dose, up to 5 years 9 months

    Outcome Measure Data

    Analysis Population Description
    Safety events were assessed in the Safety Analysis Set.
    Arm/Group Title Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Arm/Group Description All participants with advanced solid tumors who received PLX3397 600 mg BID as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment. After Cycle 1, participants were treated with PLX3397 600 mg BID and paclitaxel 80 mg/m^2 IV weekly. All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m^2 intravenous weekly as Cycle 1 lead-in treatment.
    Measure Participants 7 5 6
    Any related TEAE
    85.7
    952.2%
    100
    3333.3%
    100
    3333.3%
    Nausea
    57.1
    634.4%
    40
    1333.3%
    33.3
    1110%
    Diarrhea
    57.1
    634.4%
    20
    666.7%
    50
    1666.7%
    Constipation
    0
    0%
    40
    1333.3%
    0
    0%
    Vomiting
    0
    0%
    0
    0%
    33.3
    1110%
    Abdominal distension
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Stomatitis
    0
    0%
    40
    1333.3%
    16.7
    556.7%
    Fatigue
    42.9
    476.7%
    20
    666.7%
    83.3
    2776.7%
    Chills
    0
    0%
    0
    0%
    50
    1666.7%
    Edema peripheral
    14.3
    158.9%
    20
    666.7%
    0
    0%
    Dysgeusia
    42.9
    476.7%
    40
    1333.3%
    16.7
    556.7%
    Neuropathy peripheral
    28.6
    317.8%
    40
    1333.3%
    16.7
    556.7%
    Dizziness
    0
    0%
    0
    0%
    33.3
    1110%
    Alopecia
    42.9
    476.7%
    80
    2666.7%
    16.7
    556.7%
    Pruritus
    14.3
    158.9%
    20
    666.7%
    16.7
    556.7%
    Myalgia
    0
    0%
    0
    0%
    33.3
    1110%
    Alanine aminotransferase increased
    14.3
    158.9%
    20
    666.7%
    16.7
    556.7%
    Aspartate aminotransferase increased
    14.3
    158.9%
    20
    666.7%
    16.7
    556.7%
    Blood bilirubin increased
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Lymphocyte count decreased
    14.3
    158.9%
    0
    0%
    16.7
    556.7%
    Neutrophil count decreased
    0
    0%
    0
    0%
    33.3
    1110%
    Decreased appetite
    42.9
    476.7%
    40
    1333.3%
    16.7
    556.7%
    Anemia
    14.3
    158.9%
    20
    666.7%
    33.3
    1110%
    Neutropenia
    0
    0%
    20
    666.7%
    16.7
    556.7%

    Adverse Events

    Time Frame Adverse events and serious adverse events were recorded from the time the patient received the first dose of study drug up to 28 days after the last dose or before the start of a new anti-tumor therapy, whichever occurred first, up to 5 years 9 months.
    Adverse Event Reporting Description All-cause mortality is reported for all patients enrolled in the study. Serious and other (not including serious) adverse events are reported for the Safety Population.
    Arm/Group Title Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Arm/Group Description Participants with advanced solid tumors who received PLX3397 600 mg/day. Participants with advanced solid tumors who received PLX3397 800 mg/day. Participants with advanced solid tumors who received PLX3397 1000 mg/day. Participants with advanced solid tumors who received PLX3397 1200 mg/day. Participants with advanced solid tumors who received PLX3397 1600 mg/day. All participants with advanced solid tumors who received PLX3397 600 mg BID as lead-in treatment. All participants with advanced solid tumors who received paclitaxel 80 mg/m^2 intravenous weekly as lead-in treatment. All participants who received PLX3397 600 mg BID + paclitaxel 80 mg/m^2 intravenous weekly as lead-in treatment.
    All Cause Mortality
    Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/9 (11.1%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 5/33 (15.2%) 1/7 (14.3%) 1/6 (16.7%) 1/7 (14.3%)
    Serious Adverse Events
    Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/9 (11.1%) 1/3 (33.3%) 3/3 (100%) 2/6 (33.3%) 10/33 (30.3%) 5/7 (71.4%) 2/5 (40%) 3/6 (50%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Anemia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Lymphopenia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Neutropenia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Cardiac disorders
    Atrial fibrillation 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pericardial effusion 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Supraventricular tachycardia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Angina pectoris 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Gastrointestinal disorders
    Nausea 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Colitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 1/6 (16.7%)
    General disorders
    Pyrexia 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Sudden cardiac death 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Fatigue 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 2/7 (28.6%) 0/5 (0%) 0/6 (0%)
    Asthenia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Hepatobiliary disorders
    Mixed liver injury 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Infections and infestations
    Tooth infection 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Abscess 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Cellulitis 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Clostridium difficile colitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Device-related sepsis 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pneumonia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Puncture site infection 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Staphylococcal bacteremia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Staphylococcal infection 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Appendicitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Injury, poisoning and procedural complications
    Pelvic fracture 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Postoperative fever 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Investigations
    Blood bilirubin increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Transaminases increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Alanine aminotransferase increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 1/5 (20%) 0/6 (0%)
    Aspartate aminotransferase increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 1/5 (20%) 0/6 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Musculoskeletal and connective tissue disorders
    Pathological fracture 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor hemorrhage 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Nervous system disorders
    Syncope 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Renal and urinary disorders
    Acute kidney injury 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Reproductive system and breast disorders
    Menorrhagia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pneumothorax 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pulmonary embolism 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Epistaxis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Other (Not Including Serious) Adverse Events
    Part 1: Cohort 1; 600 mg/Day Part 1: Cohort 2; 800 mg/Day Part 1: Cohort 3; 1000 mg/Day Part 1: Cohort 4; 1200 mg/Day Part 1 and 2: Cohort 5; 1600 mg/Day Part 3: PLX3397 600 mg BID Part 3: Paclitaxel 80 mg/m^2 Part 3: PLX3397 600 mg BID + Paclitaxel 80 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%) 33/33 (100%) 7/7 (100%) 5/5 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anaemia 7/9 (77.8%) 2/3 (66.7%) 1/3 (33.3%) 2/6 (33.3%) 22/33 (66.7%) 2/7 (28.6%) 1/5 (20%) 2/6 (33.3%)
    Neutropenia 2/9 (22.2%) 1/3 (33.3%) 1/3 (33.3%) 2/6 (33.3%) 4/33 (12.1%) 0/7 (0%) 1/5 (20%) 1/6 (16.7%)
    Febrile neutropenia 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Leukopenia 2/9 (22.2%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Lymphopenia 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Thrombocytopenia 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Lymph node pain 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Thrombocytosis 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Cardiac disorders
    Tachycardia 2/9 (22.2%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pericardial effusion 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Angina pectoris 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Percarditis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Sinus arrhythmia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Ear and labyrinth disorders
    Tinnitus 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Endocrine disorders
    Hyperparathyroidism 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Eye disorders
    Periorbital oedema 0/9 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 5/33 (15.2%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Vision blurred 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 5/33 (15.2%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Lacrimation increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 5/33 (15.2%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Eye pain 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Eye swelling 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Ocular hyperaemia 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Blepharospasm 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Keratitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Visual impairment 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Gastrointestinal disorders
    Nausea 4/9 (44.4%) 1/3 (33.3%) 2/3 (66.7%) 4/6 (66.7%) 14/33 (42.4%) 5/7 (71.4%) 3/5 (60%) 4/6 (66.7%)
    Diarrhoea 3/9 (33.3%) 1/3 (33.3%) 2/3 (66.7%) 3/6 (50%) 13/33 (39.4%) 4/7 (57.1%) 2/5 (40%) 3/6 (50%)
    Vomiting 3/9 (33.3%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 12/33 (36.4%) 1/7 (14.3%) 2/5 (40%) 3/6 (50%)
    Constipation 3/9 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 7/33 (21.2%) 2/7 (28.6%) 3/5 (60%) 1/6 (16.7%)
    Dry mouth 2/9 (22.2%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/33 (9.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Stomatitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 5/33 (15.2%) 0/7 (0%) 2/5 (40%) 1/6 (16.7%)
    Dyspepsia 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 2/33 (6.1%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Abdominal pain 2/9 (22.2%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 2/7 (28.6%) 1/5 (20%) 1/6 (16.7%)
    Abdominal pain upper 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Dysphagia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Gastrooesophageal reflux disease 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Oral pain 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Abdominal distension 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 2/5 (40%) 1/6 (16.7%)
    Abdominal pain lower 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Faecal incontinence 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Gastric disorder 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Lip swelling 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Parotid gland enlargement 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Colitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 1/6 (16.7%)
    Toothache 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 1/5 (20%) 0/6 (0%)
    Ascites 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Localised intraabdominal fluid collection 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Rectal haemorrhage 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Swollen tongue 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    General disorders
    Fatigue 7/9 (77.8%) 3/3 (100%) 1/3 (33.3%) 5/6 (83.3%) 23/33 (69.7%) 3/7 (42.9%) 4/5 (80%) 6/6 (100%)
    Oedema peripheral 1/9 (11.1%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 9/33 (27.3%) 1/7 (14.3%) 2/5 (40%) 0/6 (0%)
    Pyrexia 2/9 (22.2%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 6/33 (18.2%) 0/7 (0%) 0/5 (0%) 3/6 (50%)
    Pain 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/33 (12.1%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Face oedema 0/9 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 1/6 (16.7%)
    Mucosal inflammation 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Axillary pain 1/9 (11.1%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Chest pain 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 1/5 (20%) 0/6 (0%)
    Catheter site pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Feeling jittery 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Oedema 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Sudden cardiac death 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Chills 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 4/6 (66.7%)
    Asthenia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Influenza like illness 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Localised oedema 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Peripheral swelling 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Sensation of foreign body 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Swelling 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Hepatobiliary disorders
    Mixed liver injury 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Portal vein thrombosis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Infections and infestations
    Pneumonia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/33 (12.1%) 2/7 (28.6%) 1/5 (20%) 0/6 (0%)
    Tooth infection 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Abscess 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Candidiasis 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Cellulitis 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Device related sepsis 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Puncture site infection 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Sialoadenitis 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Appendicitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Diverticulitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Fungal infection 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Gastroenteritis viral 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Nasopharyngitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Sinusitis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/33 (9.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Upper respiratory tract infection 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Urinary tract infection 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/33 (9.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pelvic fracture 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Procedural pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Radiation skin injury 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Contusion 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 1/6 (16.7%)
    Postoperative fever 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Investigations
    Aspartate aminotransferase increased 0/9 (0%) 2/3 (66.7%) 1/3 (33.3%) 2/6 (33.3%) 14/33 (42.4%) 1/7 (14.3%) 1/5 (20%) 1/6 (16.7%)
    Lymphocyte count decreased 1/9 (11.1%) 2/3 (66.7%) 1/3 (33.3%) 2/6 (33.3%) 12/33 (36.4%) 1/7 (14.3%) 0/5 (0%) 1/6 (16.7%)
    Blood creatinine phosphokinase increased 0/9 (0%) 1/3 (33.3%) 2/3 (66.7%) 1/6 (16.7%) 13/33 (39.4%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Neutrophil count decreased 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 12/33 (36.4%) 0/7 (0%) 0/5 (0%) 2/6 (33.3%)
    Alanine aminotransferase increased 0/9 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 7/33 (21.2%) 1/7 (14.3%) 1/5 (20%) 1/6 (16.7%)
    Blood alkaline phosphatase increased 0/9 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 7/33 (21.2%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Respiratory rate increased 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 4/33 (12.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Weight decreased 1/9 (11.1%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 2/33 (6.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Platelet count decreased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Activated partial thromboplastin time prolonged 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Blood lactate dehydrogenase increased 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Blood potassium decreased 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hematocrit decreased 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hemoglobin decreased 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    International normalised ratio increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pulmonary physical examination abnormal 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Weight increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Blood bilirubin increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 1/6 (16.7%)
    Blood creatinine increased 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Liver function test abnormal 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Metabolism and nutrition disorders
    Decreased appetite 7/9 (77.8%) 1/3 (33.3%) 0/3 (0%) 4/6 (66.7%) 12/33 (36.4%) 3/7 (42.9%) 3/5 (60%) 1/6 (16.7%)
    Hypokalaemia 2/9 (22.2%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 9/33 (27.3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hypophosphataemia 1/9 (11.1%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 8/33 (24.2%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hypoalbuminaemia 1/9 (11.1%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 3/33 (9.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Dehydration 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/33 (12.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hyperuricaemia 0/9 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hyponatraemia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/33 (12.1%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Hyperglycaemia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/33 (9.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hypocalcaemia 1/9 (11.1%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hypomagnesaemia 0/9 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Vitamin D deficiency 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/9 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 3/33 (9.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pain in extremity 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/33 (12.1%) 1/7 (14.3%) 1/5 (20%) 2/6 (33.3%)
    Myalgia 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 2/6 (33.3%)
    Neck pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/33 (9.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Back pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Flank pain 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Groin pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Muscular weakness 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Musculoskeletal chest pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Muscle spasms 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Musculoskeletal discomfort 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Musculoskeletal pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Nervous system disorders
    Dysgeusia 1/9 (11.1%) 0/3 (0%) 1/3 (33.3%) 3/6 (50%) 12/33 (36.4%) 3/7 (42.9%) 2/5 (40%) 2/6 (33.3%)
    Dizziness 3/9 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 4/33 (12.1%) 2/7 (28.6%) 1/5 (20%) 2/6 (33.3%)
    Neuropathy peripheral 2/9 (22.2%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 4/33 (12.1%) 2/7 (28.6%) 3/5 (60%) 1/6 (16.7%)
    Headache 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 4/33 (12.1%) 1/7 (14.3%) 1/5 (20%) 1/6 (16.7%)
    Hypoaesthesia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 3/33 (9.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Peripheral sensory neuropathy 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Tremor 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Disturbance in attention 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Dyskinesia 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hemiparesis 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Paraesthesia 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Sensory disturbance 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Somnolence 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Sciatica 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Syncope 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Psychiatric disorders
    Insomnia 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 5/33 (15.2%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Confusional state 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Anxiety 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Depression 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Renal and urinary disorders
    Pollakiuria 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Urinary incontinence 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 1/6 (16.7%)
    Dysuria 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 1/6 (16.7%)
    Acute kidney injury 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Incontinence 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Micturition urgency 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Reproductive system and breast disorders
    Vaginal haemorrhage 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 1/5 (20%) 0/6 (0%)
    Menorrhagia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 2/9 (22.2%) 1/3 (33.3%) 0/3 (0%) 3/6 (50%) 11/33 (33.3%) 2/7 (28.6%) 2/5 (40%) 2/6 (33.3%)
    Cough 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 6/33 (18.2%) 1/7 (14.3%) 2/5 (40%) 0/6 (0%)
    Pleural effusion 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 3/33 (9.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Epistaxis 1/9 (11.1%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 2/33 (6.1%) 1/7 (14.3%) 2/5 (40%) 1/6 (16.7%)
    Dysphonia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 4/33 (12.1%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Dyspnoea exertional 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Oropharyngeal pain 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 1/7 (14.3%) 1/5 (20%) 0/6 (0%)
    Productive cough 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Tachypnoea 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Chronic obstructive pulmonary disease 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hiccups 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Nasal congestion 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pleuritic pain 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Pulmonary embolism 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Sleep apnoea syndrome 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Wheezing 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hypoxia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Lung infiltration 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Rhinorrhoea 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/9 (11.1%) 1/3 (33.3%) 1/3 (33.3%) 4/6 (66.7%) 8/33 (24.2%) 3/7 (42.9%) 4/5 (80%) 1/6 (16.7%)
    Rash 1/9 (11.1%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 9/33 (27.3%) 0/7 (0%) 2/5 (40%) 0/6 (0%)
    Pruritus 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 5/33 (15.2%) 1/7 (14.3%) 1/5 (20%) 1/6 (16.7%)
    Erythema 1/9 (11.1%) 0/3 (0%) 2/3 (66.7%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Night sweats 2/9 (22.2%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Dry skin 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Rash maculo-papular 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Dermatitis acneiform 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Hair colour changes 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Nail disorder 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Petechiae 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Seborrhoea 1/9 (11.1%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Swelling face 0/9 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Urticaria 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Ecchymosis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Hyperhidrosis 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 0/7 (0%) 0/5 (0%) 1/6 (16.7%)
    Nail discolouration 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Onychalgia 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/33 (0%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Palmar-plantar erythrodysaesthesia syndrome 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/33 (3%) 1/7 (14.3%) 0/5 (0%) 0/6 (0%)
    Vascular disorders
    Hypertension 1/9 (11.1%) 2/3 (66.7%) 0/3 (0%) 3/6 (50%) 10/33 (30.3%) 0/7 (0%) 0/5 (0%) 3/6 (50%)
    Systolic hypertension 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 3/33 (9.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Hot flush 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Embolism 0/9 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 2/33 (6.1%) 0/7 (0%) 0/5 (0%) 0/6 (0%)
    Flushing 0/9 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/33 (0%) 0/7 (0%) 1/5 (20%) 0/6 (0%)
    Hypotension 0/9 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/33 (3%) 0/7 (0%) 0/5 (0%) 0/6 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Medical Director
    Organization Daiichi Sankyo Inc.
    Phone 908-992-6400
    Email CTRinfo@dsi.com
    Responsible Party:
    Daiichi Sankyo, Inc.
    ClinicalTrials.gov Identifier:
    NCT01525602
    Other Study ID Numbers:
    • PLX108-07
    First Posted:
    Feb 3, 2012
    Last Update Posted:
    Jul 16, 2020
    Last Verified:
    Jul 1, 2020