Trial Outcomes & Findings for Phase II Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Treating Patients With Stage IV Melanoma (NCT NCT01970527)

NCT ID: NCT01970527

Last Updated: 2020-02-13

Results Overview

Scored on a non-index lesion using immune-related response criteria according to immune-related Response Evaluation Criteria in Solid Tumors version 1.1. The number of immune-related responses will be tabled by stratum and SBRT fraction dose level. At the MTD, the immune-related response rate and 95% exact confidence interval will be estimated separately for previously untreated and previously treated metastatic patients.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: Up to 60 days after last ipilimumab injection
• Results posted on: 2020-02-13

Participant Flow

As of January 2018, 23 participants consented to the study during accrual duration of 36 months. The participants with metastatic melanoma were recruited from the clinic at Department of Radiation Oncology, University of Washington Medical Center.

The total number of participants that consented to the study are 23, however 1 participant was a screen-fail due to brain metastasis.

Participant milestones

Measure	Bone or Lung Index Lesion Participants with bone or lung index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 8 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 24 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.	Liver or Subcutaneous Index Lesion Participants with liver or subcutaneous index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 6 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 18 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.
Pre-treatment/Baseline STARTED	9	14
Pre-treatment/Baseline COMPLETED	8	14
Pre-treatment/Baseline NOT COMPLETED	1	0
Treatment STARTED	8	14
Treatment COMPLETED	8	11
Treatment NOT COMPLETED	0	3
Follow-up Clinic Visit STARTED	8	11
Follow-up Clinic Visit COMPLETED	7	8
Follow-up Clinic Visit NOT COMPLETED	1	3

Reasons for withdrawal

Measure	Bone or Lung Index Lesion Participants with bone or lung index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 8 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 24 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.	Liver or Subcutaneous Index Lesion Participants with liver or subcutaneous index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 6 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 18 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.
Pre-treatment/Baseline Screen fail- participant had brain mets	1	0
Treatment Disease progression	0	1
Treatment Participant did not tolerate Ipilimumab	0	1
Treatment Death	0	1
Follow-up Clinic Visit Disease progression	1	1
Follow-up Clinic Visit Withdrawal by Subject	0	1
Follow-up Clinic Visit Lost to Follow-up	0	1

Baseline Characteristics

Phase II Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Treating Patients With Stage IV Melanoma

Baseline characteristics by cohort

Measure	Bone or Lung Index Lesion n=9 Participants Participants with bone or lung index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 8 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 24 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.	Liver or Subcutaneous Index Lesion n=14 Participants Participants with liver or subcutaneous index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 6 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 18 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	14 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	14 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 60 days after last ipilimumab injection

Population: Arms were stratified during tx for safety reasons, but the stated objective to calculate response rate per strata was re-assessed. Due to low accrual per-strata calculations lack the statistical power to draw robust conclusions. Results were not stratified during the statistical analysis of the study data and are reported as such here.

Scored on a non-index lesion using immune-related response criteria according to immune-related Response Evaluation Criteria in Solid Tumors version 1.1. The number of immune-related responses will be tabled by stratum and SBRT fraction dose level. At the MTD, the immune-related response rate and 95% exact confidence interval will be estimated separately for previously untreated and previously treated metastatic patients.

Outcome measures

Measure	Stable Disease n=22 Participants Patients with Stable disease at any point in follow up	Immune Resistant Previously treated metastatic melanoma patients
Immune-related Clinical Response, Defined as Proportion of Patients Treated at the Maximum-tolerated Dose (MTD) Who Achieve Either a Complete or Partial Immune-related Response	6 Participants	—

PRIMARY outcome

Timeframe: Time from first day of radiotherapy to first documented immune-related progressive disease, death due to any cause or last patient contact alive and progression-free, assessed at 6 months

Population: Arms were stratified during tx for safety reasons, but the stated objective to calculate response rate per strata was re-assessed. Due to low accrual per-strata calculations lack the statistical power to draw robust conclusions. Results were not stratified during the statistical analysis of the study data and are reported as such here.

irPFS will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD..

For some patients no scans were available for irRECIST reads, in which case change of management was determined to be the point of progression.

Outcome measures

Measure	Stable Disease n=15 Participants Patients with Stable disease at any point in follow up	Immune Resistant n=6 Participants Previously treated metastatic melanoma patients
Immune-related Progression-free Survival (irPFS)	131 Days Standard Deviation 30.4	121 Days Standard Deviation 50.3

PRIMARY outcome

Timeframe: Up to 3 years

Defined generally as an adverse event associated with the treatment which occurs beyond 30 days after last injection (i.e., adverse events which are observed months after treatment are most likely associated with SBRT). All dose-limiting toxicities and late toxicities will be graded and tabled by lesion site stratum and SBRT fraction dose level. Toxicity attribution to either SBRT or ipilimumab will be described if possible.

Outcome measures

Measure	Stable Disease n=8 Participants Patients with Stable disease at any point in follow up	Immune Resistant n=14 Participants Previously treated metastatic melanoma patients
Late Toxicities, Graded According to the Radiation Therapy Oncology Group/European Organization for Research, the Treatment of Cancer Late Morbidity Scoring System, and the Common Terminology Criteria for Adverse Events Version 4.0	2 Participants	1 Participants

PRIMARY outcome

Timeframe: Time from first day of radiotherapy to death due to any cause or last patient contact alive, assessed at 12 months

Population: Arms were stratified during tx for safety reasons, but the stated objective to calculate response rate per strata was re-assessed. Due to low accrual per-strata calculations lack the statistical power to draw robust conclusions. Results were not stratified during the statistical analysis of the study data and are reported.

Will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.

Outcome measures

Measure	Stable Disease n=16 Participants Patients with Stable disease at any point in follow up	Immune Resistant n=6 Participants Previously treated metastatic melanoma patients
Overall Survival	154 Days Standard Deviation 327.6	307.5 Days Standard Deviation 282.8

Adverse Events

Bone or Lung Index Lesion

Serious events: 1 serious events

Other events: 8 other events

Deaths: 4 deaths

Liver or Subcutaneous Index Lesion

Serious events: 1 serious events

Other events: 14 other events

Deaths: 11 deaths

Serious adverse events

Measure	Bone or Lung Index Lesion n=8 participants at risk Participants with bone or lung index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 8 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 24 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.	Liver or Subcutaneous Index Lesion n=14 participants at risk Participants with liver or subcutaneous index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 6 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 18 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.
Cardiac disorders Atrial flutter and Shortness of Breath	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.

Other adverse events

Measure	Bone or Lung Index Lesion n=8 participants at risk Participants with bone or lung index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 8 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 24 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.	Liver or Subcutaneous Index Lesion n=14 participants at risk Participants with liver or subcutaneous index lesion with prescription dose per fraction to the Planning Target Volume (PTV) of 6 Gy per fraction. The total dose for dose level 1 (our starting dose level) will be 18 Gy over 3 fractions. If we encounter a dose limiting toxicity, we will then reduce our total dose to dose level -1. The total dose for dose level -1 will be 12 Gy over 2 fractions.
Gastrointestinal disorders Colitis	25.0% 2/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Diarrhea	62.5% 5/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	42.9% 6/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Fatigue	75.0% 6/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	35.7% 5/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Fevers	25.0% 2/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Chills	25.0% 2/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Nausea	37.5% 3/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Pain	100.0% 8/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	92.9% 13/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Skin and subcutaneous tissue disorders Pruritis	62.5% 5/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	42.9% 6/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Skin and subcutaneous tissue disorders Rash	37.5% 3/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	35.7% 5/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Investigations Weight loss	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Bloating	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Blood in stool	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Reproductive system and breast disorders Burning sensation at inguinal area	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Constipation	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Renal and urinary disorders Dark/Blood urine	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Hemorroids	25.0% 2/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Endocrine disorders Hypophysitis	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Respiratory, thoracic and mediastinal disorders Lump in throat	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Malaise	25.0% 2/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Vomiting	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Nervous system disorders Headache	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	42.9% 6/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Respiratory, thoracic and mediastinal disorders Cough	62.5% 5/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Cardiac disorders Hypertension	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Cardiac disorders Hypercholesterolemia	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Insomnia	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Psychiatric disorders Anxiety	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Respiratory, thoracic and mediastinal disorders Shortness of breath	25.0% 2/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Eye disorders Hemianopsia	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	21.4% 3/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Reproductive system and breast disorders Lump in right breast	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Worsening balance	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Nervous system disorders Lower jaw instability	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Bruising from fall	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Tingling in toes	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Vascular disorders Edema (Lower extremities)	25.0% 2/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Investigations Anemia	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Hernia	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Skin and subcutaneous tissue disorders Cancer sores	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Soft stool	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Dry mouth	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Nervous system disorders Numbness	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Psychiatric disorders Weepy/teary	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Skin and subcutaneous tissue disorders Cyst on left breast	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Respiratory, thoracic and mediastinal disorders Wheezing	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Swelling on right axillary region	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Stomach ache	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Nervous system disorders Lightheadedness	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Heartburn	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Swelling in right neck	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Psychiatric disorders Depression	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Dysgeusia	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Musculoskeletal and connective tissue disorders Cramps	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Night sweats	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Hair loss	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Loss of appetite	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Ear and labyrinth disorders Tinnitus	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Light sensitivity	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Tenderness/warmth of left neck	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Skin and subcutaneous tissue disorders Hypopigmentation	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	14.3% 2/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Skin and subcutaneous tissue disorders Redness in axilla	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Anorexia	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Respiratory, thoracic and mediastinal disorders Pneumonia	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Gastrointestinal disorders Mucositis	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
General disorders Hemoptysis	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Psychiatric disorders Altered mental status	12.5% 1/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	0.00% 0/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Investigations Hypokalemia	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.
Investigations Leukocytosis	0.00% 0/8 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.	7.1% 1/14 • 36 months The study period during which adverse events must be reported is normally defined as the period from the initiation of any study procedures to the end of the study treatment follow-up. For this study, the study treatment follow-up is defined as 30 days following the last administration of study treatment. Thereafter, only non-hematological related AEs of Grade 3 and can reasonably be attributed to the study treatment will be reported.

Additional Information

Dr. Ramesh Rengan

University of Washington Medical Center

Phone: 206-598-4100

Email: rengan@uw.edu

Results disclosure agreements

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