Trial Outcomes & Findings for Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer (NCT NCT01664182)

Last Updated: 2022-06-07

Results Overview

Defined as the total number of efficacy-evaluable patients who achieve a complete or partial response by RECIST version 1.1 criteria, assessed by MRI: Complete Response (CR), Disappearance of all target lesions: any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Best response will be listed for each patient and summarized using standard descriptive methods-point estimate and associated confidence intervals.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Up to 8 weeks

Results posted on

2022-06-07

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Trebananib Monotherapy) Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV
Overall Study STARTED	19	22
Overall Study COMPLETED	17	18
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Trebananib Monotherapy) n=17 Participants Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) n=18 Participants Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV	Total n=35 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	59 years n=7 Participants	60 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants	18 participants n=7 Participants	35 participants n=5 Participants
ECOG Performance Score 0	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
ECOG Performance Score 1	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Prior Anti-VEGF Agent Bevacizumab	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Prior Anti-VEGF Agent Pazopanib	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Prior Anti-VEGF Agent Sorafenib	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Prior Anti-VEGF Agent Sunitinib	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 8 weeks

Outcome measures

Outcome measures
Measure	Arm I (Trebananib Monotherapy) n=17 Participants Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) n=18 Participants Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV
Observed Response Rate	0 percentage of patients responding Interval 0.0 to 20.0	11 percentage of patients responding Interval 1.0 to 35.0

PRIMARY outcome

Timeframe: at 8 weeks

Tumor Response Classification

Outcome measures

Outcome measures
Measure	Arm I (Trebananib Monotherapy) n=17 Participants Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) n=18 Participants Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV
Tumor Response Partial Response	0 Participants	2 Participants
Tumor Response Stable Disease	5 Participants	8 Participants
Tumor Response Progressive Disease	11 Participants	6 Participants
Tumor Response Not Evaluable	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first, assessed up to 8 weeks

Time to reach Kaplan-Meier median survival (outcome being death or progression) (95% Confidence Interval) is reported. Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered a progression.)

Outcome measures

Outcome measures
Measure	Arm I (Trebananib Monotherapy) n=17 Participants Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) n=18 Participants Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV
Progression Free Survival (PFS)	2.7 months Interval 2.3 to 4.7	5.2 months Interval 2.7 to 10.8

SECONDARY outcome

Timeframe: 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks

Adverse events were graded using CTCAE version 5.0. Grades 3, 4, 5 (on a scale of 1 to 5, 5 being the worst grade - death) toxicities related ('Possibly', 'Probably', or 'Definitely') to the treatment drugs (AMG 386 alone or in combination with prior VEGF targeted agent).

Outcome measures

Outcome measures
Measure	Arm I (Trebananib Monotherapy) n=17 Participants Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) n=18 Participants Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Blood and lymphatic system disorders: Anemia	0 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Investigations: Weight gain	0 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Metabolism and nutrition disorders: Hyponatremia	0 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs SAE Cardiac disorders: Cardiac arrest	0 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs SAE Metabolism and nutrition disorders: Hypokalemia	1 Participants	0 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs SAE Respiratory, thoracic and mediastinal disorders: Dyspnea	1 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs SAE Respiratory, thoracic and mediastinal disorders: Pleural effusion	1 Participants	0 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs General disorders and administrative site conditions: Fatigue	1 Participants	3 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Investigations: Lymphocyte count decreased	0 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Metabolism and nutrition disorders: Acidosis	0 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Metabolism and nutrition disorders: Hyperglycemia	1 Participants	0 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Musculoskeletal and connective tissue disorders: Back pain	1 Participants	1 Participants
Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs Vascular disorders: Hypertension	3 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 8 weeks

Population: availability of samples. attrition from the study.

Analyzed as continuous variables (most likely after transformation). The gene expression results from the pretreatment tumor biopsies are expressed as ratios between that of the gene of interest and the internal reference gene beta-actin and can be analyzed as continuous variables - generally after log transformation.

Outcome measures

Outcome measures
Measure	Arm I (Trebananib Monotherapy) n=17 Participants Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) n=18 Participants Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV
Changes in Circulating Angiogenic Factors ICAM--1 at baseline	161879 pg/ml Interval 103645.0 to 240620.0	243594 pg/ml Interval 185653.0 to 601003.0
Changes in Circulating Angiogenic Factors VCAM--1 prior to cycle 2	1336300 pg/ml Interval 955663.0 to 1903550.0	1850000 pg/ml Interval 1327000.0 to 2555600.0
Changes in Circulating Angiogenic Factors Angiopoietin--2 at baseline	3909 pg/ml Interval 3246.0 to 4863.0	3237 pg/ml Interval 2424.0 to 4813.0
Changes in Circulating Angiogenic Factors Angiopoietin--2 prior to cycle 2	132156 pg/ml Interval 110775.0 to 160316.0	120956 pg/ml Interval 84474.0 to 131643.0
Changes in Circulating Angiogenic Factors Angiopoietin--2 prior to cycle 3	125928 pg/ml Interval 114871.0 to 141528.0	96075 pg/ml Interval 84200.0 to 150486.0
Changes in Circulating Angiogenic Factors Tie--2 at baseline	803 pg/ml Interval 510.0 to 1035.0	835 pg/ml Interval 650.0 to 1094.0
Changes in Circulating Angiogenic Factors Tie--2 prior to cycle 2	783 pg/ml Interval 535.0 to 1041.0	671 pg/ml Interval 571.0 to 856.0
Changes in Circulating Angiogenic Factors Tie--2 prior to cycle 3	912 pg/ml Interval 263.0 to 1232.0	753 pg/ml Interval 424.0 to 912.0
Changes in Circulating Angiogenic Factors VEGF--A at baseline	27.3 pg/ml Interval 10.5 to 48.4	26.1 pg/ml Interval 19.6 to 38.0
Changes in Circulating Angiogenic Factors VEGF--A prior to cycle 2	21.3 pg/ml Interval 10.5 to 29.0	33.4 pg/ml Interval 13.6 to 48.2
Changes in Circulating Angiogenic Factors VEGF--A prior to cycle 3	20.7 pg/ml Interval 0.3 to 34.2	41.2 pg/ml Interval 26.1 to 56.7
Changes in Circulating Angiogenic Factors PIGF at baseline	31.1 pg/ml Interval 26.1 to 35.2	30.7 pg/ml Interval 28.3 to 46.7
Changes in Circulating Angiogenic Factors PIGF prior to cycle 2	30.5 pg/ml Interval 21.8 to 36.0	33.6 pg/ml Interval 29.9 to 39.2
Changes in Circulating Angiogenic Factors PIGF prior to cycle 3	31.4 pg/ml Interval 30.5 to 34.3	31.5 pg/ml Interval 26.3 to 41.8
Changes in Circulating Angiogenic Factors VEGFR--3 at baseline	873 pg/ml Interval 157.0 to 1073.0	489 pg/ml Interval 50.0 to 898.0
Changes in Circulating Angiogenic Factors VEGFR--3 prior to cycle 2	722 pg/ml Interval 117.0 to 869.0	50 pg/ml Interval 50.0 to 321.0
Changes in Circulating Angiogenic Factors VEGFR--3 prior to cycle 3	489 pg/ml Interval 362.0 to 954.0	50 pg/ml Interval 50.0 to 416.0
Changes in Circulating Angiogenic Factors VEGF--C at baseline	255 pg/ml Interval 72.0 to 425.0	283 pg/ml Interval 251.0 to 380.0
Changes in Circulating Angiogenic Factors VEGF--C prior to cycle 2	209 pg/ml Interval 67.0 to 340.0	311 pg/ml Interval 247.0 to 357.0
Changes in Circulating Angiogenic Factors VEGF--C prior to cycle 3	230 pg/ml Interval 45.0 to 358.0	311 pg/ml Interval 154.0 to 503.0
Changes in Circulating Angiogenic Factors IL--8 at baseline	0.1 pg/ml Interval 0.1 to 12.6	0.1 pg/ml Interval 0.1 to 4.0
Changes in Circulating Angiogenic Factors IL--8 prior to cycle 2	3.6 pg/ml Interval 0.1 to 17.5	5.9 pg/ml Interval 0.1 to 13.5
Changes in Circulating Angiogenic Factors IL--8 prior to cycle 3	2.5 pg/ml Interval 0.1 to 8.1	0.4 pg/ml Interval 0.1 to 17.3
Changes in Circulating Angiogenic Factors ICAM--1 prior to cycle 2	193335 pg/ml Interval 117584.0 to 247434.0	239027 pg/ml Interval 160295.0 to 318968.0
Changes in Circulating Angiogenic Factors ICAM--1 prior to cycle 3	262636 pg/ml Interval 221161.0 to 266594.0	200959 pg/ml Interval 150610.0 to 276615.0
Changes in Circulating Angiogenic Factors VCAM--1 at baseline	965554 pg/ml Interval 738499.0 to 1421550.0	1307900 pg/ml Interval 982643.0 to 1946700.0
Changes in Circulating Angiogenic Factors VCAM--1 prior to cycle 3	982488 pg/ml Interval 969237.0 to 1581000.0	1666200 pg/ml Interval 1351500.0 to 2091050.0
Changes in Circulating Angiogenic Factors FGF2 at baseline	124 pg/ml Interval 105.0 to 136.0	120 pg/ml Interval 105.0 to 136.0
Changes in Circulating Angiogenic Factors FGF2 prior to cycle 2	112 pg/ml Interval 89.0 to 131.0	110 pg/ml Interval 95.0 to 132.0
Changes in Circulating Angiogenic Factors FGF2 prior to cycle 3	131 pg/ml Interval 104.0 to 136.0	120 pg/ml Interval 97.0 to 133.0
Changes in Circulating Angiogenic Factors PDGF -- AA at baseline	351 pg/ml Interval 237.0 to 788.0	478 pg/ml Interval 112.0 to 647.0
Changes in Circulating Angiogenic Factors PDGF -- AA prior to cycle 2	291 pg/ml Interval 190.0 to 394.0	262 pg/ml Interval 213.0 to 829.0
Changes in Circulating Angiogenic Factors PDGF -- AA prior to cycle 3	264 pg/ml Interval 119.0 to 710.0	173 pg/ml Interval 105.0 to 777.0

Adverse Events

Arm I (Trebananib Monotherapy)

Serious events: 10 serious events

Other events: 16 other events

Deaths: 0 deaths

Arm II (Trebananib and Anti-VEGF Therapy)

Serious events: 18 serious events

Other events: 18 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Thomas J Semrad, MD, MAS

Gene Upshaw Memorial Tahoe Forest Cancer Center, Truckee, CA 96161

Phone: +1 530 582 6450

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Trebananib Monotherapy) n=17 participants at risk Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Trebananib: Given IV	Arm II (Trebananib and Anti-VEGF Therapy) n=18 participants at risk Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Pazopanib Hydrochloride: Given PO Sorafenib Tosylate: Given PO Sunitinib Malate: Given PO Trebananib: Given IV
Cardiac disorders Cardiac arrest	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Cardiac disorders Myocardial infarction	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	11.1% 2/18 • Number of events 2 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Gastrointestinal disorders Diarrhea	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Gastrointestinal disorders Nausea	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Gastrointestinal disorders Vomiting	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Infections and infestations Skin infection	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Infections and infestations Suspected pneumonia	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Infections and infestations Urinary tract infection	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	0.00% 0/18 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Infections and infestations Urosepsis	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	0.00% 0/18 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Investigations Lymphocyte count decreased	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Metabolism and nutrition disorders Hyperglycemia	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	0.00% 0/18 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Metabolism and nutrition disorders Hypokalemia	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	0.00% 0/18 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Musculoskeletal and connective tissue disorders Back pain	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	0.00% 0/18 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive Disease	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Nervous system disorders Peripheral sensory neuropathy	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	0.00% 0/18 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Renal and urinary disorders Acute kidney injury	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	11.1% 2/18 • Number of events 2 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Renal and urinary disorders Chronic kidney disease	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	16.7% 3/18 • Number of events 3 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.9% 1/17 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.
Vascular disorders Hypotension	0.00% 0/17 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.	5.6% 1/18 • Number of events 1 • 8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks CTCAE version 4.0 will be used until March 31, 2018. CTCAE version 5.0 will be used from April 1, 2018.