Trial Outcomes & Findings for Pivotal Study in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer (NCT NCT03786094)

NCT ID: NCT03786094

Last Updated: 2023-11-01

Results Overview

To evaluate the efficacy of balixafortide + eribulin versus eribulin monotherapy on the primary endpoint of progression free survival (PFS). PFS, as assessed by the Independent Review Committee, defined as the time from the date of randomization to the earliest evidence of documented progressive disease or death from any cause. Patients who were alive without postbaseline assessments or without documented progressive disease, lost to follow-up, withdrew consent, started an anticancer therapy prior to observing a progressive disease or with an event documented after 2 or more missing tumor assessments were censored. PFS was evaluated according to RECIST v1.1 guidelines for complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 432 participants
• Primary outcome timeframe: Patients received treatment until PD by RECIST v1.1 criteria was met or until one of the treatment discontinuation or study withdrawal criteria was met.
• Results posted on: 2023-11-01

Participant Flow

Participant milestones

Measure	Balixafortide + Eribulin Balixafortide: Balixafortide + Eribulin Balixafortide was administered as a single IV administration (5.5 mg/kg over at least 2 hours \[±10 minutes\]) on Days 1-3 and Days 8-10 of each 21-day cycle. Eribulin was administered IV at a dose of 1.4 mg/m2 over 2 to 5 minutes on Days 2 and 9 of each 21-day cycle.	Eribulin Monotherapy Eribulin was administered as a single IV administration (1.4 mg/m2 over 2-5 minutes) on Days 2 and 9 of each 21-day cycle.
Overall Study STARTED	219	213
Overall Study Overall Population (2nd Line+)	219	213
Overall Study 3rd Line+ Population	175	173
Overall Study COMPLETED	10	11
Overall Study NOT COMPLETED	209	202

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pivotal Study in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	Balixafortide + Eribulin n=219 Participants Balixafortide: Balixafortide + Eribulin	Eribulin Monotherapy n=213 Participants Eribulin: Eribulin alone	Total n=432 Participants Total of all reporting groups
Age, Continuous	54.5 years STANDARD_DEVIATION 10.87 • n=5 Participants	55.6 years STANDARD_DEVIATION 11.07 • n=7 Participants	55.0 years STANDARD_DEVIATION 10.97 • n=5 Participants
Sex: Female, Male Female	218 Participants n=5 Participants	211 Participants n=7 Participants	429 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants	19 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	197 Participants n=5 Participants	174 Participants n=7 Participants	371 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Breast Cancer History Time since first diagnosis of breast cancer	6.99 years STANDARD_DEVIATION 6.096 • n=5 Participants	7.21 years STANDARD_DEVIATION 5.647 • n=7 Participants	7.10 years STANDARD_DEVIATION 5.873 • n=5 Participants
Breast Cancer History Time since diagnosis of locally recurrent or metastatic disease	2.96 years STANDARD_DEVIATION 2.503 • n=5 Participants	3.15 years STANDARD_DEVIATION 2.427 • n=7 Participants	3.05 years STANDARD_DEVIATION 2.464 • n=5 Participants

PRIMARY outcome

Timeframe: Patients received treatment until PD by RECIST v1.1 criteria was met or until one of the treatment discontinuation or study withdrawal criteria was met.

Population: Overall Population (2nd Line+)

To evaluate the efficacy of balixafortide + eribulin versus eribulin monotherapy on the primary endpoint of progression free survival (PFS). PFS, as assessed by the Independent Review Committee, defined as the time from the date of randomization to the earliest evidence of documented progressive disease or death from any cause. Patients who were alive without postbaseline assessments or without documented progressive disease, lost to follow-up, withdrew consent, started an anticancer therapy prior to observing a progressive disease or with an event documented after 2 or more missing tumor assessments were censored.

PFS was evaluated according to RECIST v1.1 guidelines for complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).

Outcome measures

Measure	Balixafortide + Eribulin n=219 Participants Balixafortide: Balixafortide + Eribulin	Eribulin Monotherapy n=213 Participants Eribulin: Eribulin alone
Progression Free Survival (2nd Line+ Population)	3.5 months Interval 2.8 to 4.2	4.0 months Interval 3.0 to 4.3

PRIMARY outcome

Timeframe: Patients received treatment until PD by RECIST v1.1 criteria was met or until one of the treatment discontinuation or study withdrawal criteria was met.

Population: 3rd Line+ Population

To evaluate the efficacy of balixafortide + eribulin versus eribulin monotherapy on the primary endpoint of progression free survival (PFS). PFS, as assessed by the Independent Review Committee, defined as the time from the date of randomization to the earliest evidence of documented progressive disease or death from any cause. Patients who were alive without postbaseline assessments or without documented progressive disease, lost to follow-up, withdrew consent, started an anticancer therapy prior to observing a progressive disease or with an event documented after 2 or more missing tumor assessments were censored.

PFS was evaluated according to RECIST v1.1 guidelines for complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).

Outcome measures

Measure	Balixafortide + Eribulin n=175 Participants Balixafortide: Balixafortide + Eribulin	Eribulin Monotherapy n=173 Participants Eribulin: Eribulin alone
Progression Free Survival (3rd Line+ Population)	3.5 months Interval 2.8 to 4.2	4.0 months Interval 2.9 to 4.2

SECONDARY outcome

Timeframe: The Investigator monitored the patient for OS status every 6 months (or more frequently) until: death, the patient withdrew consent to follow-up for survival, or until the patient was lost to follow-up (whichever occurred first).

Population: 3rd Line+ Population

To compare the overall survival (OS) between patients in the balixafortide + eribulin treatment arm versus eribulin monotherapy treatment arm. OS is defined as the time from date of randomization to date of death due to any cause. Patients who are lost to follow-up or are not known to have died at the time of data-cut-off for analysis or who do not have any follow up since randomization were censored.

Outcome measures

Measure	Balixafortide + Eribulin n=175 Participants Balixafortide: Balixafortide + Eribulin	Eribulin Monotherapy n=173 Participants Eribulin: Eribulin alone
Overall Survival (3rd Line+ Population)	11.0 months Interval 8.9 to 12.3	11.2 months Interval 8.9 to 14.0

Adverse Events

Balixafortide + Eribulin

Serious events: 62 serious events

Other events: 214 other events

Deaths: 17 deaths

Eribulin Monotherapy

Serious events: 54 serious events

Other events: 197 other events

Deaths: 13 deaths

Serious adverse events

Measure	Balixafortide + Eribulin n=218 participants at risk Balixafortide: Balixafortide + Eribulin	Eribulin Monotherapy n=204 participants at risk Eribulin: Eribulin alone
Infections and infestations Urosepsis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Pneumonia	2.3% 5/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	2.5% 5/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations COVID-19 pneumonia	1.4% 3/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	2.5% 5/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Sepsis	1.4% 3/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	1.5% 3/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Device related infection	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.98% 2/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Erysipelas	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Neutropenic infection	0.92% 2/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Urinary tract infection	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Arthritis infective	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Atypical pneumonia	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Breast cellulitis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations COVID-19	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Dermatitis infected	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Escherichia bacteraemia	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Gastroenteritis	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Pseudomonal sepsis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Septic shock	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Sinusitis	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Infections and infestations Tonsillitis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Blood and lymphatic system disorders Febrile neutropenia	2.3% 5/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	4.4% 9/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Blood and lymphatic system disorders Anaemia	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.98% 2/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Blood and lymphatic system disorders Neutropenia	0.92% 2/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Blood and lymphatic system disorders Lymphadenopathy mediastinal	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.8% 4/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.98% 2/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.8% 4/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.98% 2/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Immune-mediated pneumonitis	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
General disorders Disease progression	2.3% 5/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	2.5% 5/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
General disorders General physical health deterioration	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
General disorders Asthenia	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
General disorders Multiple organ dysfunction syndrome	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Bone pain	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Pathological fracture	0.92% 2/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Arthritis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Musculoskeletal and connective tissue disorders Spinal pain	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Injury, poisoning and procedural complications Infusion related reaction	2.3% 5/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Injury, poisoning and procedural complications Femur fracture	0.92% 2/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Injury, poisoning and procedural complications Ankle fracture	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Injury, poisoning and procedural complications Hip fracture	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Injury, poisoning and procedural complications Humerus fracture	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Injury, poisoning and procedural complications Tibia fracture	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Constipation	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Diarrhoea	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Gastritis	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Malignant gastrointestinal obstruction	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Nausea	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Oesophageal compression	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Peptic ulcer	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Stomatitis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Syncope	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Brain oedema	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Cerebrovascular accident	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Chronic inflammatory demyelinating polyradiculoneuropathy	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Epilepsy	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Hemiparesis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Transient ischaemic attack	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	1.5% 3/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Dehydration	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Diabetes mellitus	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Hypocalcaemia	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.92% 2/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Malignant pleural effusion	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Metastases to central nervous system	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Hepatobiliary disorders Acute hepatic failure	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Hepatobiliary disorders Cholecystitis acute	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Hepatobiliary disorders Drug-induced liver injury	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Hepatobiliary disorders Hepatic failure	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Renal and urinary disorders Renal failure	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Renal and urinary disorders Acute kidney injury	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Renal and urinary disorders Chronic kidney disease	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Cardiac disorders Cardiac tamponade	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Cardiac disorders Myocardial infarction	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Cardiac disorders Sinus tachycardia	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Vascular disorders Hypotension	0.92% 2/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Vascular disorders Superior vena cava syndrome	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Investigations Electrocardiogram QT prolonged	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Investigations Transaminases increased	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Psychiatric disorders Confusional state	0.46% 1/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Surgical and medical procedures Lens extraction	0.00% 0/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.

Other adverse events

Measure	Balixafortide + Eribulin n=218 participants at risk Balixafortide: Balixafortide + Eribulin	Eribulin Monotherapy n=204 participants at risk Eribulin: Eribulin alone
Skin and subcutaneous tissue disorders Alopecia	27.1% 59/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	30.4% 62/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Skin and subcutaneous tissue disorders Pruritus	25.2% 55/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.49% 1/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Skin and subcutaneous tissue disorders Rash	10.6% 23/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Blood and lymphatic system disorders Neutropenia	26.1% 57/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	33.3% 68/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Blood and lymphatic system disorders Anaemia	12.4% 27/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	16.2% 33/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Blood and lymphatic system disorders Leukopenia	8.3% 18/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	9.8% 20/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
General disorders Asthenia	18.8% 41/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	19.6% 40/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
General disorders Fatigue	13.3% 29/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	17.2% 35/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
General disorders Pyrexia	5.0% 11/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	6.4% 13/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Nausea	20.2% 44/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	19.6% 40/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Diarrhoea	7.8% 17/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	13.2% 27/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Stomatitis	11.5% 25/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	5.4% 11/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Constipation	7.3% 16/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	9.3% 19/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Gastrointestinal disorders Vomiting	6.4% 14/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	5.4% 11/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Investigations Neutrophil count decreased	15.6% 34/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	17.2% 35/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Investigations Alanine aminotransferase increased	6.4% 14/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	7.4% 15/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Investigations White blood cell count decreased	5.5% 12/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	7.8% 16/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Investigations Aspartate aminotransferase increased	3.7% 8/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	8.8% 18/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Neuropathy peripheral	8.3% 18/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	6.9% 14/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Dysgeusia	5.5% 12/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	4.9% 10/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Nervous system disorders Peripheral sensory neuropathy	5.5% 12/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	4.9% 10/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Injury, poisoning and procedural complications Infusion related reaction	43.6% 95/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	0.00% 0/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.
Metabolism and nutrition disorders Decreased appetite	10.1% 22/218 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.	5.9% 12/204 • 5 months For the purposes of the clinical study report, a treatment-emergent adverse event (TEAE) was considered to have occurred at a similar rate between treatment arms if the percentage difference between arms was \<5.0%. TEAEs were defined as AEs that occurred at or after administration of the first dose of any study treatment and through 30 days after the last dose of any study treatment.

Additional Information

Christian Zwingelstein

Spexis AG

Phone: +41 61 567 16 00

Email: info@spexisbio.com

Results disclosure agreements

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