Trial Outcomes & Findings for MAGE-A3 Protein + AS15 as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation (NCT NCT01380145)

NCT ID: NCT01380145

Last Updated: 2022-10-25

Results Overview

Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs, with severity graded according to the NCI CTCAE, Version 4.0.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 13 participants
• Primary outcome timeframe: Continuously for up to 14 months
• Results posted on: 2022-10-25

Participant Flow

Participant milestones

Measure	All Enrolled Subjects Subjects received a total of 8 pre- and post-auto-SCT immunizations with recMAGE-A3 + AS15 administered intramuscularly at a dose of 300 µg recMAGE-A3, with no dose adjustments permitted. The first immunization was administered 6 to 15 week prior to auto-SCT, with subsequent immunizations administered on Days 10, 31, 52, 73, and 94 (± 3 days) and Days 180 and 270 (± 7 days) after auto-SCT.
Overall Study STARTED	13
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure

All Enrolled Subjects Subjects received a total of 8 pre- and post-auto-SCT immunizations with recMAGE-A3 + AS15 administered intramuscularly at a dose of 300 µg recMAGE-A3, with no dose adjustments permitted. The first immunization was administered 6 to 15 week prior to auto-SCT, with subsequent immunizations administered on Days 10, 31, 52, 73, and 94 (± 3 days) and Days 180 and 270 (± 7 days) after auto-SCT.

Overall Study Progressive disease

4

Baseline Characteristics

MAGE-A3 Protein + AS15 as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Baseline characteristics by cohort

Measure	All Enrolled Subjects n=13 Participants Includes all subjects enrolled in the study.
Age, Continuous	54.3 years STANDARD_DEVIATION 10.33 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants
Body Mass Index	30.2 kg/m^2 STANDARD_DEVIATION 4.74 • n=5 Participants
Response to Prior Induction Therapy Complete Response	1 participants n=5 Participants
Response to Prior Induction Therapy Very Good Partial Response	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Continuously for up to 14 months

Population: The Safety Analysis Set comprises all subjects who received at least 1 immunization with study drug.

Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs, with severity graded according to the NCI CTCAE, Version 4.0.

Outcome measures

Measure	Safety Analysis Set n=13 Participants Includes all subjects who received at least 1 immunization with study drug.
Assessment of Safety of recMAGE-A3 + AS15 Any TEAE	13 participants
Assessment of Safety of recMAGE-A3 + AS15 Grade 3 TEAE	8 participants
Assessment of Safety of recMAGE-A3 + AS15 Grade 4 TEAE	4 participants
Assessment of Safety of recMAGE-A3 + AS15 Grade 5 TEAE (Death)	0 participants
Assessment of Safety of recMAGE-A3 + AS15 Treatment-related TEAE	10 participants
Assessment of Safety of recMAGE-A3 + AS15 SAE	4 participants
Assessment of Safety of recMAGE-A3 + AS15 TEAE leading to withdrawal	0 participants

SECONDARY outcome

Timeframe: Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT

Population: The Immunogenicity Analysis Set comprises all subjects who received at least 1 immunization with study drug and had a baseline and at least 1 post-baseline immunity assessment.

Humoral immunity was determined by enzyme-linked immunosorbent assay (ELISA) to measure the presence of circulating antibodies to MAGE-A3. Titers against an antigen were considered significant if they were >100. Induction of responses was considered significant if there was a change from undetectable (<100) to detectable (>100) or if there was an at least 4-fold increase in titers over time.

Outcome measures

Measure	Safety Analysis Set n=13 Participants Includes all subjects who received at least 1 immunization with study drug.
Induction or Augmentation of MAGE-A3-Specific Humoral Immunity Seroconversion after 1 immunization	3 participants
Induction or Augmentation of MAGE-A3-Specific Humoral Immunity Seroconversion after 2 immunizations	8 participants
Induction or Augmentation of MAGE-A3-Specific Humoral Immunity Seroconversion after 3-4 immunizations	2 participants

SECONDARY outcome

Timeframe: Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT

Population: The Immunogenicity Analysis Set comprises all subjects who received at least 1 immunization with study drug and had a baseline and at least 1 post-baseline immunity assessment.

Cellular immunity was determined by enzyme-linked immunosorbent spot assay (ELISPOT) or intracellular flow cytometry to determine peripheral blood levels of interferon gamma-producing CD4+ and CD8+ T cells specific for MAGE-A3. Results were considered significant if > 50 spots and > 2 times the number of spots to negative control were observed.

Outcome measures

Measure	Safety Analysis Set n=13 Participants Includes all subjects who received at least 1 immunization with study drug.
Induction or Augmentation of MAGE-A3-Specific Cellular Immunity Post-immunization CD4 T-cell response/increase	13 participants
Induction or Augmentation of MAGE-A3-Specific Cellular Immunity Baseline CD8 T cell response	0 participants
Induction or Augmentation of MAGE-A3-Specific Cellular Immunity Post-immunization CD8 T-cell response/increase	3 participants
Induction or Augmentation of MAGE-A3-Specific Cellular Immunity Baseline CD4 T cell response	6 participants

SECONDARY outcome

Timeframe: At 3 and 12 months after auto-SCT

Population: The Evaluable Analysis Set comprises all subjects who received at least 1 immunization with study drug and had a baseline and at least 1 post-baseline disease assessment.

Tumor responses were evaluated using appropriate imaging methods and were categorized according to the IMWG criteria, which includes the following response designations:

Complete Response (CR): negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% plasma cells in bone marrow; Stringent CR (sCR): CR + normal free light chain (FLC) ratio and absence of clonal cells in bone marrow; Very Good Partial Response (VGPR): Serum/urine M-component detectable by immunofixation but not electropheresis OR ≥90% reduction in serum M-component + urine M-component <100 mg/24 hrs; Partial Response (PR): ≥50% reduction of serum M-protein and reduction in 24-hr urinary M-protein by ≥90% or to <200 mg/24 hrs Stable disease: not response or progression

Outcome measures

Measure	Safety Analysis Set n=13 Participants Includes all subjects who received at least 1 immunization with study drug.
Assessment of Tumor Response Day 94: Stringent Complete Response	2 participants
Assessment of Tumor Response Day 94: Very Good Partial Response	8 participants
Assessment of Tumor Response Day 360: Stringent Complete Response	4 participants
Assessment of Tumor Response Day 360: Complete Response	1 participants
Assessment of Tumor Response Day 360: Very Good Partial Response	4 participants
Assessment of Tumor Response Day 94: Complete Response	3 participants
Assessment of Tumor Response Day 360: Progressive Disease	4 participants

SECONDARY outcome

Timeframe: Continuously on study and for up to 5 years post-study

Population: The Evaluable Analysis Set comprises all subjects who received at least 1 immunization with study drug and had a baseline and at least 1 post-baseline disease assessment.

Progression-free survival (PFS) was calculated as the date from first immunization to first observation of disease progression or death due to any cause, censored on the start date of subsequent therapy or at the last date of disease assessment for subjects without a PFS event. Overall survival (OS) was calculated as the date from first immunization to death due to any cause, censored at the date of last follow-up for subjects who were alive at the time of the analysis. Time to subsequent therapy was calculated as the date from first immunization to start of subsequent therapy for myeloma, censored at the date of death or last follow-up for subjects who did not receive subsequent therapy.

Outcome measures

Measure	Safety Analysis Set n=13 Participants Includes all subjects who received at least 1 immunization with study drug.
Assessment of Survival and Time to Subsequent Therapy Median PFS using the Kaplan-Meier Method	751 days Interval 379.0 to Upper limit of the confidence interval was not reached.
Assessment of Survival and Time to Subsequent Therapy Median OS using the Kaplan-Meier Method	829 days Interval 829.0 to Upper limit of the confidence interval was not reached.
Assessment of Survival and Time to Subsequent Therapy Median Time to Subsequent Therapy using Kaplan-Meier Method	805 days Interval 414.0 to Upper limit of the confidence interval was not reached.

Adverse Events

Safety Analysis Set

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	Safety Analysis Set n=13 participants at risk Includes all subjects who received at least 1 immunization with study drug.
Skin and subcutaneous tissue disorders Psoriasis	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Connective tissue disorder	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Diarrhoea	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Nausea	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Injection site reaction	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Myalgia	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Cardiac disorders Atrial fibrillation	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	7.7% 1/13 • Number of events 1 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.

Other adverse events

Measure	Safety Analysis Set n=13 participants at risk Includes all subjects who received at least 1 immunization with study drug.
Gastrointestinal disorders Nausea	69.2% 9/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Fatigue	61.5% 8/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Decreased appetite	53.8% 7/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Diarrhoea	46.2% 6/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Oedema peripheral	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Blood and lymphatic system disorders Thrombocytopenia	46.2% 6/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Bone pain	38.5% 5/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Constipation	38.5% 5/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Headache	38.5% 5/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Psychiatric disorders Insomnia	38.5% 5/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Alopecia	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Blood and lymphatic system disorders Anaemia	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Blood and lymphatic system disorders Febrile neutropenia	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Hypokalaemia	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Injection site reaction	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Injection site pain	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Mucosal inflammation	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Paraesthesia	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Pyrexia	30.8% 4/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Abdominal pain	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Psychiatric disorders Anxiety	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Vascular disorders Flushing	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Blood and lymphatic system disorders Leukopenia	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Neuropathy peripheral	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Rash	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Sinusitis	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Upper respiratory tract infection	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Urticaria	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Vomiting	23.1% 3/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Arthralgia	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Chest discomfort	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Chills	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Cough	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Dizziness	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Dyspepsia	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Hypocalcaemia	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Hypomagnesaemia	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Influenza like illness	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Myalgia	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Blood and lymphatic system disorders Neutropenia	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	15.4% 2/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Acute sinusitis	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Psychiatric disorders Agitation	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Investigations Blood testosterone decreased	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Bronchitis	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Diabetes mellitus	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Immune system disorders Drug hypersensitivity	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Dry mouth	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Dry skin	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Dysgeusia	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Fungal skin infection	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Renal and urinary disorders Haematuria	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Vascular disorders Hypertension	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Hypoalbuminaemia	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Vascular disorders Hypotension	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Infection	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Influenza	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Infusion related reaction	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Injury, poisoning and procedural complications Ligament rupture	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Malaise	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Muscular weakness	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Nail discolouration	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Nodule	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Non-cardiac chest pain	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Oedema	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Oral pain	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Vascular disorders Orthostatic hypotension	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Musculoskeletal and connective tissue disorders Osteopenia	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Peripheral sensory neuropathy	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Pneumonia	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Proctalgia	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Gastrointestinal disorders Proctitis	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Skin and subcutaneous tissue disorders Pruritus	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Respiratory, thoracic and mediastinal disorders Sinus congestion	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Somnolence	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Injury, poisoning and procedural complications Stress fracture	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Nervous system disorders Syncope	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Urinary tract infection	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Reproductive system and breast disorders Vaginal haemorrhage	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
General disorders Vessel puncture site reaction	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Metabolism and nutrition disorders Vitamin K deficiency	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Infections and infestations Vulvitis	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Investigations Weight increased	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Ear and labyrinth disorders Ear disorder	7.7% 1/13 • All AEs occurring between the date of enrollment and the off-study date (i.e., for up to 14 months) were documented, regardless of the causal relationship to study drug. AEs occurring or worsening after the first dose of study drug were considered treatment emergent (i.e., TEAEs). AE documentation included onset/resolution dates, severity using NCI CTCAE (v4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.

Additional Information

Jonathan Skipper PhD

Ludwig Institute for Cancer Research

Phone: 12124501539

Email: jskipper@lcr.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60