Trial Outcomes & Findings for Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in People With Previously Untreated Metastatic Colorectal Cancer QUILT-2.004 (NCT NCT03050814)

Last Updated: 2021-12-20

Results Overview

Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and 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. The appearance of one or more new lesions is also considered progressions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Up to 1.5 years

Results posted on

2021-12-20

Participant Flow

Participant milestones

Participant milestones
Measure	Standard of Care (SOC) - Arm A Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day. 5-Fluorouracil (FU): 400mg/m\^2 intravenous (IV) bolus on day 1. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 1. Oxaliplatin: 85mg/m\^2 intravenous (IV) over 2 hours on day 1. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1.	Standard of Care (SOC) - Arm B + Lead in Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression. Avelumab: 10 mg/kg intravenous (IV) over 30-60 min on day 1 Ad-CEA vaccine: Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day 2. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 2. Oxaliplatin: 68mg/m\^2 intravenous (IV) over 2 hours on day 2. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on day 2.	Enrolled But Not Assigned to a Treatment Arm 4 participants were enrolled but not treated on Arm A or Arm B. Only baseline data were captured.
Overall Study STARTED	10	16	4
Overall Study COMPLETED	10	16	0
Overall Study NOT COMPLETED	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard of Care (SOC) - Arm A Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day. 5-Fluorouracil (FU): 400mg/m\^2 intravenous (IV) bolus on day 1. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 1. Oxaliplatin: 85mg/m\^2 intravenous (IV) over 2 hours on day 1. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1.	Standard of Care (SOC) - Arm B + Lead in Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression. Avelumab: 10 mg/kg intravenous (IV) over 30-60 min on day 1 Ad-CEA vaccine: Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day 2. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 2. Oxaliplatin: 68mg/m\^2 intravenous (IV) over 2 hours on day 2. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on day 2.	Enrolled But Not Assigned to a Treatment Arm 4 participants were enrolled but not treated on Arm A or Arm B. Only baseline data were captured.
Overall Study Screen failures	0	0	4

Baseline Characteristics

Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in People With Previously Untreated Metastatic Colorectal Cancer QUILT-2.004

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care (SOC) - Arm A n=10 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day. 5-Fluorouracil (FU): 400mg/m\^2 intravenous (IV) bolus on day 1. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 1. Oxaliplatin: 85mg/m\^2 intravenous (IV) over 2 hours on day 1. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1.	Standard of Care (SOC) - Arm B + Lead in n=16 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression. Avelumab: 10 mg/kg intravenous (IV) over 30-60 min on day 1 Ad-CEA vaccine: Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day 2. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 2. Oxaliplatin: 68mg/m\^2 intravenous (IV) over 2 hours on day 2. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on day 2.	Enrolled But Not Assigned to a Treatment Arm n=4 Participants 4 participants were enrolled but not treated on Arm A or Arm B. Only baseline data were captured.	Total n=30 Participants Total of all reporting groups
Age, Continuous	57.94 years STANDARD_DEVIATION 10.65 • n=5 Participants	56.34 years STANDARD_DEVIATION 8.45 • n=7 Participants	59.17 years STANDARD_DEVIATION 23.3 • n=5 Participants	57.82 years STANDARD_DEVIATION 14.13 • n=4 Participants
Age, Customized <= 18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized Between 18 and 65 years	9 Participants n=5 Participants	12 Participants n=7 Participants	2 Participants n=5 Participants	23 Participants n=4 Participants
Age, Customized >= 65 years	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Age, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	11 Participants n=7 Participants	1 Participants n=5 Participants	15 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	15 Participants n=7 Participants	4 Participants n=5 Participants	28 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	13 Participants n=7 Participants	3 Participants n=5 Participants	22 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	16 participants n=7 Participants	4 participants n=5 Participants	30 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 1.5 years

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) - Arm A n=10 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day. 5-Fluorouracil (FU): 400mg/m\^2 intravenous (IV) bolus on day 1. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 1. Oxaliplatin: 85mg/m\^2 intravenous (IV) over 2 hours on day 1. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1.	Standard of Care (SOC) - Arm B + Lead in n=16 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression. Avelumab: 10 mg/kg intravenous (IV) over 30-60 min on day 1 Ad-CEA vaccine: Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day 2. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 2. Oxaliplatin: 68mg/m\^2 intravenous (IV) over 2 hours on day 2. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on day 2.
Progression Free Survival Between the Standard of Care (SOC) Arm A, and Standard of Care (SOC) Arm B + lead-in	8.8 Months Interval 3.3 to 17.0	10.1 Months Interval 3.6 to 16.1

SECONDARY outcome

Timeframe: Up to 51.5 months

Participants hospitalized because of adverse events measured by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 attributed to disease progression. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and 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. The appearance of one or more new lesions is also considered progressions.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) - Arm A n=10 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day. 5-Fluorouracil (FU): 400mg/m\^2 intravenous (IV) bolus on day 1. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 1. Oxaliplatin: 85mg/m\^2 intravenous (IV) over 2 hours on day 1. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1.	Standard of Care (SOC) - Arm B + Lead in n=16 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression. Avelumab: 10 mg/kg intravenous (IV) over 30-60 min on day 1 Ad-CEA vaccine: Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day 2. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 2. Oxaliplatin: 68mg/m\^2 intravenous (IV) over 2 hours on day 2. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on day 2.
Number of Participants That Are Hospitalized Because of Adverse Events Attributed to Disease Progression	4 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) - Arm A n=10 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day. 5-Fluorouracil (FU): 400mg/m\^2 intravenous (IV) bolus on day 1. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 1. Oxaliplatin: 85mg/m\^2 intravenous (IV) over 2 hours on day 1. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1.	Standard of Care (SOC) - Arm B + Lead in n=16 Participants Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression. Avelumab: 10 mg/kg intravenous (IV) over 30-60 min on day 1 Ad-CEA vaccine: Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day 2. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 2. Oxaliplatin: 68mg/m\^2 intravenous (IV) over 2 hours on day 2. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on day 2.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	10 Participants	16 Participants

Adverse Events

Standard of Care (SOC) - Arm A

Serious events: 9 serious events

Other events: 10 other events

Deaths: 1 deaths

Standard of Care (SOC) - Arm B + Lead in

Serious events: 10 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Julius Y. Strauss

National Cancer Institute

Phone: 240-858-3999

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Standard of Care (SOC) - Arm A n=10 participants at risk Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine until disease progression. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day. 5-Fluorouracil (FU): 400mg/m\^2 intravenous (IV) bolus on day 1. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 1. Oxaliplatin: 85mg/m\^2 intravenous (IV) over 2 hours on day 1. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on Day 1.	Standard of Care (SOC) - Arm B + Lead in n=16 participants at risk Participants will receive leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX)- + bevacizumab + avelumab + Ad-CEA vaccine (given weeks 0,2,4,8,12,16 and then every 12 weeks) for up to 12 2-week cycles followed by maintenance therapy with bevacizumab + capecitabine + avelumab + Ad-CEA vaccine (following the every 12-week dosing schedule) until disease progression. Avelumab: 10 mg/kg intravenous (IV) over 30-60 min on day 1 Ad-CEA vaccine: Subcutaneous injection in the thigh prior to Avelumab on Day 1 of cycles 1, 2 3, 5, 7, 9; every 6 cycles thereafter. Bevacizumab: 5mg/kg intravenous (IV) over 30-90 min on day 2. Leucovorin: 400mg/m\^2 intravenous (IV) over 2 hours on day 2. Oxaliplatin: 68mg/m\^2 intravenous (IV) over 2 hours on day 2. Capecitabine: 625 mg/m\^2 twice a day by mouth. 5-Fluorouracil (FU): 2400 mg/m\^2 intravenous (IV) over 46 hours (+/-2 hours) to start on day 2.
Gastrointestinal disorders Abdominal pain	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Metabolism and nutrition disorders Acidosis	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Blood and lymphatic system disorders Anemia	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Gastrointestinal disorders Ascites	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Cardiac disorders Atrial fibrillation	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Cardiac disorders Cardiac disorders - Other, coronary vasospasm	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Investigations Creatinine increased	10.0% 1/10 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
General disorders Death NOS	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Gastrointestinal disorders Diarrhea	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
General disorders Fatigue	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Blood and lymphatic system disorders Febrile neutropenia	20.0% 2/10 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Metabolism and nutrition disorders Hypoalbuminemia	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Metabolism and nutrition disorders Hypokalemia	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Vascular disorders Hypotension	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Infections and infestations Infections and infestations - Other, ureter	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
General disorders Injection site reaction	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Infections and infestations Lung infection	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Gastrointestinal disorders Nausea	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, death	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Investigations Neutrophil count decreased	20.0% 2/10 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
General disorders Pain	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Investigations Platelet count decreased	10.0% 1/10 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Renal and urinary disorders Renal and urinary disorders - Other, anuric renal failure	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Infections and infestations Sepsis	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Cardiac disorders Sinus tachycardia	10.0% 1/10 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Infections and infestations Sinusitis	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Gastrointestinal disorders Small intestinal obstruction	10.0% 1/10 • Number of events 3 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Surgical and medical procedures Surgical and medical procedures - Other, Cystoscopy	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Infections and infestations Upper respiratory infection	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Gastrointestinal disorders Vomiting	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Investigations White blood cell decreased	10.0% 1/10 • Number of events 2 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Surgical and medical procedures Surgical and medical procedures - Other, specify	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Surgical and medical procedures Surgical and medical procedures - Other, Hepatic RFA, Biopsy	0.00% 0/10 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.
Surgical and medical procedures Surgical and medical procedures - Other, hepatic ablation	10.0% 1/10 • Number of events 1 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.	0.00% 0/16 • Date treatment consent signed to date off study, approximately 33 months and 20 days for Arm A and 51 months and 7 days for Arm B.