Trial Outcomes & Findings for Morphotek Investigation in Colorectal Cancer: Research of MORAb-004 (MICRO) (NCT NCT01507545)

Last Updated: 2022-05-06

Results Overview

PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 was defined as the time (in weeks) from the date of randomization to the date of the first observation of disease progression (PD) or death due to any cause. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of last tumor assessment without evidence of progression prior to the date of initiation of further antitumor treatment. PFS was summarized for each treatment group using Kaplan-Meier estimation curves.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

154 participants

Primary outcome timeframe

From the date of randomization to the date of the first observation of PD or death due to any cause (up to approximately 1 year 7 months)

Results posted on

2022-05-06

Participant Flow

Participants took part in the study at 61 investigative sites in the United States from 27 March 2012 to 20 October 2013.

A total of 154 participants were screened and enrolled (signed informed consent form), of which 28 were screen failures, 126 were randomized and 122 were treated. Study was terminated by the sponsor at the end of Stage 1 due to futility, hence Stage 2 was not carried out.

Participant milestones

Participant milestones
Measure	MORAb-004 8.0 mg/kg + BSC Participants received MORAb-004 8 milligram per kilogram (mg/kg), infusion intravenously (IV), once weekly, in each 2-week treatment cycle along with the best supportive care (BSC) which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Overall Study STARTED	84	42
Overall Study Treated/Safety Set	82	40
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	84	42

Reasons for withdrawal

Reasons for withdrawal
Measure	MORAb-004 8.0 mg/kg + BSC Participants received MORAb-004 8 milligram per kilogram (mg/kg), infusion intravenously (IV), once weekly, in each 2-week treatment cycle along with the best supportive care (BSC) which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Overall Study Withdrawal by Subject	6	2
Overall Study Lost to Follow-up	1	0
Overall Study Discontinuation of the study by sponsor	11	9
Overall Study Progressive disease	60	27
Overall Study Other	6	4

Baseline Characteristics

Morphotek Investigation in Colorectal Cancer: Research of MORAb-004 (MICRO)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MORAb-004 8.0 mg/kg + BSC n=84 Participants Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC n=42 Participants Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Total n=126 Participants Total of all reporting groups
Age, Continuous	61.4 years STANDARD_DEVIATION 11.72 • n=93 Participants	61.8 years STANDARD_DEVIATION 10.61 • n=4 Participants	61.5 years STANDARD_DEVIATION 11.32 • n=27 Participants
Sex: Female, Male Female	43 Participants n=93 Participants	16 Participants n=4 Participants	59 Participants n=27 Participants
Sex: Female, Male Male	41 Participants n=93 Participants	26 Participants n=4 Participants	67 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=93 Participants	1 Participants n=4 Participants	7 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	75 Participants n=93 Participants	40 Participants n=4 Participants	115 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Asian	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) White	74 Participants n=93 Participants	36 Participants n=4 Participants	110 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the date of the first observation of PD or death due to any cause (up to approximately 1 year 7 months)

Population: ITT population included all randomized participants, analyzed according to the treatment assigned by the IVRS/IWRS.

Outcome measures

Outcome measures
Measure	MORAb-004 8.0 mg/kg + BSC n=84 Participants Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC n=42 Participants Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Progression-Free Survival (PFS)	8.1 weeks Interval 7.9 to 8.1	8.1 weeks Interval 8.0 to 8.3

SECONDARY outcome

Timeframe: From the date of randomization to the date of death due to any cause (up to approximately 1 year 7 months)

Population: ITT population included all randomized participants, analyzed according to the treatment assigned by IVRS/IWRS.

OS was defined as the time (in months) from the date of randomization to the date of death, regardless of the cause. OS was summarized for each treatment group using Kaplan-Meier estimation curves. In the absence of death confirmation or for participants alive at the time of analysis, the survival time was censored at the last date known to be alive.

Outcome measures

Outcome measures
Measure	MORAb-004 8.0 mg/kg + BSC n=84 Participants Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC n=42 Participants Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Overall Survival (OS)	4.8 months Interval 3.7 to 6.2	6.2 months Interval 4.7 to 9.7

SECONDARY outcome

Timeframe: From the date of randomization to the first documentation of CR or PR (up to approximately 1 year 7 months)

Population: ITT population included all randomized participants, analyzed according to the treatment assigned by IVRS/IWRS.

ORR was defined as the percentage of subjects achieving either CR or PR using RECIST v.1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	MORAb-004 8.0 mg/kg + BSC n=84 Participants Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC n=42 Participants Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Overall Response Rate (ORR)	0 percentage of participants Interval 0.0 to 4.296	2.4 percentage of participants Interval 0.06 to 12.566

SECONDARY outcome

Timeframe: From the date of randomization to first documentation of objective tumor response (CR or PR) (up to approximately 1 year 7 months)

Population: ITT population included all randomized participants, analyzed according to the treatment assigned by the IVRS/IWRS. Here overall number analyzed "N" are the participants who had achieved CR or PR.

Time to tumor response was defined for those participants with objective evidence of confirmed CR or PR as the time from randomization to first documentation of objective tumor response (CR or PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	MORAb-004 8.0 mg/kg + BSC Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC n=1 Participants Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Time to Tumor Response (TTR)	—	NA weeks Data for TTR were not estimable because of low response rate (CR or PR) among all participants.

SECONDARY outcome

Timeframe: From the date of first objective response (CR or PR) to objective tumor progression or death regardless of cause (up to approximately 1 year 7 months)

The DOR was defined as the time from first documentation of objective response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	MORAb-004 8.0 mg/kg + BSC Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC n=1 Participants Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Duration of Response (DOR)	—	NA weeks Data for DOR were not estimable because of low response rate (CR or PR) among all participants.

SECONDARY outcome

Timeframe: From the date of randomization up to approximately 1 year 7 months

Population: The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for PFS was not carried out.

The statistical evidence to support the use of the biomarker identified in Stage 1 interim analysis for Stage 2 selection of participants as designed was not adequate to clearly define a biomarker responsive population. The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for PFS was not carried out.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the date of randomization up to approximately 1 year 7 months

Population: The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for OS was not carried out.

Outcome measures

Outcome data not reported

Adverse Events

MORAb-004 8.0 mg/kg + BSC

Serious events: 31 serious events

Other events: 77 other events

Deaths: 13 deaths

Placebo + BSC

Serious events: 15 serious events

Other events: 40 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai Inc.

Phone: 1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	MORAb-004 8.0 mg/kg + BSC n=82 participants at risk Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Placebo + BSC n=40 participants at risk Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Blood and lymphatic system disorders Anaemia	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Blood and lymphatic system disorders Neutropenia	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Abdominal Pain	3.7% 3/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Small Intestinal Obstruction	3.7% 3/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Ascites	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Caecitis	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Constipation	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Intestinal Obstruction	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Gastrointestinal disorders Rectal Haemorrhage	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
General disorders Pyrexia	2.4% 2/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	5.0% 2/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
General disorders Asthenia	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
General disorders Fatigue	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
General disorders Gait Disturbance	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Hepatobiliary disorders Hepatic Failure	3.7% 3/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Infections and infestations Abdominal Wall Abscess	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Infections and infestations Intestinal Fistula Infection	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Infections and infestations Pneumonia	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Infections and infestations Septic Shock	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Injury, poisoning and procedural complications Infusion Related Reaction	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Metabolism and nutrition disorders Dehydration	6.1% 5/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	5.0% 2/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Metabolism and nutrition disorders Hypocalcaemia	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Metabolism and nutrition disorders Hypokalaemia	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Musculoskeletal and connective tissue disorders Back Pain	4.9% 4/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Musculoskeletal and connective tissue disorders Muscular Weakness	2.4% 2/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm Malignant	8.5% 7/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	5.0% 2/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases To Central Nervous System	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Nervous system disorders Hypoaesthesia	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Nervous system disorders Cauda Equina Syndrome	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Nervous system disorders Headache	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Nervous system disorders Presyncope	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Psychiatric disorders Confusional State	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Renal and urinary disorders Renal Failure Acute	2.4% 2/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Renal and urinary disorders Renal Failure	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Renal and urinary disorders Urinary Tract Obstruction	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 2/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Respiratory, thoracic and mediastinal disorders Respiratory Failure	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Vascular disorders Deep Vein Thrombosis	2.4% 2/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	2.5% 1/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Vascular disorders Embolism	2.4% 2/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
General disorders General Physical Health Deterioration	1.2% 1/82 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)	0.00% 0/40 • From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)