Trial Outcomes & Findings for Pembrolizumab in Patients With Non-Small Cell Lung Cancer and a Performance Status 2 (NCT NCT02733159)

NCT ID: NCT02733159

Last Updated: 2025-02-10

Results Overview

Adverse events will be recorded in relation to each cycle of treatment and graded according to CTCAE criteria. The toxicity co-primary outcome measure for the trial is defined as the occurrence of a treatment-related dose delay or treatment discontinuation due to toxicity.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 62 participants
• Primary outcome timeframe: Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment)
• Results posted on: 2025-02-10

Participant Flow

The trial opened to recruitment on 7th November 2016 and the first patient was recruited on 4th January 2017. The trial was opened to recruitment at 10 National Health Service (NHS) hospitals across the United Kingdom. The last patient was recruited on 13th February 2018.

Participant milestones

Measure	Pembrolizumab Pembrolizumab: 200 mg Q3W (once every 3 weeks), intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Overall Study STARTED	62
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Pembrolizumab Pembrolizumab: 200 mg Q3W (once every 3 weeks), intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Overall Study Adverse Event	1
Overall Study Lack of disease progression	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Pembrolizumab n=62 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Age, Continuous Age at Registration (years)	69.85 years n=62 Participants
Sex: Female, Male Female	28 Participants n=62 Participants
Sex: Female, Male Male	34 Participants n=62 Participants
Histology Adenocarcinoma	43 Participants n=62 Participants
Histology Adenosquamous Carcinoma	0 Participants n=62 Participants
Histology Squamous Cell Carcinoma	12 Participants n=62 Participants
Histology Not Otherwise Specified	1 Participants n=62 Participants
Histology Other	6 Participants n=62 Participants
Smoking Status Current smoker	11 Participants n=62 Participants
Smoking Status Ex-smoker	45 Participants n=62 Participants
Smoking Status Never smoked	3 Participants n=62 Participants
Smoking Status Not Known	3 Participants n=62 Participants
Smoking Pack Years	43.78 years n=56 Participants • Only given for patients who self-identified as either current or ex-smokers.
Duration of Abstinence	15.38 years n=45 Participants • Only given for patients who self-identified as ex-smokers
Charlson Co-Morbidity Index Score	7.58 units on a scale n=62 Participants
Charlson Co-Morbidity Index Score 0	3 Participants n=62 Participants
Charlson Co-Morbidity Index Score 1	0 Participants n=62 Participants
Charlson Co-Morbidity Index Score 2	1 Participants n=62 Participants
Charlson Co-Morbidity Index Score 3	4 Participants n=62 Participants
Charlson Co-Morbidity Index Score 4	4 Participants n=62 Participants
Charlson Co-Morbidity Index Score 5	4 Participants n=62 Participants
Charlson Co-Morbidity Index Score 6	2 Participants n=62 Participants
Charlson Co-Morbidity Index Score 7	3 Participants n=62 Participants
Charlson Co-Morbidity Index Score 8	7 Participants n=62 Participants
Charlson Co-Morbidity Index Score 9	19 Participants n=62 Participants
Charlson Co-Morbidity Index Score 10	9 Participants n=62 Participants
Charlson Co-Morbidity Index Score 11	2 Participants n=62 Participants
Charlson Co-Morbidity Index Score 12	4 Participants n=62 Participants
Sample Type Archived biopsy sample	52 Participants n=59 Participants • Only given for patients who had a successful PD-L1 staining of the tumour sample.
Sample Type New biopsy sample	7 Participants n=59 Participants • Only given for patients who had a successful PD-L1 staining of the tumour sample.
Percentage of Tumour Cells Expressing PD-L1	24.89 % n=59 Participants • Only given for patients who had a successful PD-L1 staining of the tumour sample.
PD-L1 Staining Result Negative (<1%)	28 Participants n=59 Participants • Only given for patients who had a successful PD-L1 staining of the tumour sample.
PD-L1 Staining Result Positive (1-49%)	16 Participants n=59 Participants • Only given for patients who had a successful PD-L1 staining of the tumour sample.
PD-L1 Staining Result Strong Positive (50-100%)	15 Participants n=59 Participants • Only given for patients who had a successful PD-L1 staining of the tumour sample.
Line of Therapy First	25 Participants n=62 Participants
Line of Therapy Subsequent	37 Participants n=62 Participants
Previous Therapy Biological	2 participants n=62 Participants • Items are non-exclusive; a patient could have multiple previous therapies.
Previous Therapy Chemotherapy	44 participants n=62 Participants • Items are non-exclusive; a patient could have multiple previous therapies.
Previous Therapy Immunological	1 participants n=62 Participants • Items are non-exclusive; a patient could have multiple previous therapies.
Previous Therapy Radiotherapy	28 participants n=62 Participants • Items are non-exclusive; a patient could have multiple previous therapies.
Previous Therapy Surgery	13 participants n=62 Participants • Items are non-exclusive; a patient could have multiple previous therapies.

PRIMARY outcome

Timeframe: Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment)

Adverse events will be recorded in relation to each cycle of treatment and graded according to CTCAE criteria. The toxicity co-primary outcome measure for the trial is defined as the occurrence of a treatment-related dose delay or treatment discontinuation due to toxicity.

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Toxicity Rate Patients Experiencing Toxicity Event	18 Participants
Toxicity Rate Patients Not Experiencing Toxicity Event	42 Participants

PRIMARY outcome

Timeframe: ≥18 weeks, up to maximum of 2 years

Patients will have CT scans every 9 weeks from baseline until disease progression. On each occasion, overall tumour burden will be assessed using RECIST version 1.1. The efficacy co-primary outcome measure for the trial is durable clinical benefit defined as the occurrence of CR, PR or SD without prior progressive disease at or after the second scheduled CT scan (scheduled to occur at 18 weeks).

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Durable Clinical Benefit Patients Experiencing Durable Clinical Benefits Event	22 Participants
Durable Clinical Benefit Patients Not Experiencing DCB Event	38 Participants

SECONDARY outcome

Timeframe: ≥18 weeks, up to maximum of 2 years

Objective response (OR) is the occurrence of Complete Response (CR) or Partial Response (PR) as the best overall response. OR will be based on responses confirmed using the subsequent 9-weekly scan but OR based on unconfirmed responses will also be reported.

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Objective Response No	44 Participants
Objective Response Yes	16 Participants

SECONDARY outcome

Timeframe: Through study completion, up to a maximum of 2 years

This is defined as the functional effect of a medical condition and/or its consequent treatment upon a patient. The purpose of Health Related Quality of Life (HRQoL) measurement is to quantify the degree to which the medical condition or its treatment impacts the individual's life in a valid and reproducible way. HRQoL will be assessed over time using Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire and EQ-5D questionnaire.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time to progression up to 2 years

This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded. Patients with no recorded progression at the time of analysis or who die without recorded progression will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Time to Progression	11.9 months Interval 4.13 to 27.8

SECONDARY outcome

Timeframe: Progression-free survival time up to 2 years

This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression. Patients who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Progression-free Survival Time	4.39 months Interval 3.48 to 9.9

SECONDARY outcome

Timeframe: Survival time up to 2 years or date of death

This is defined as the time from commencement of trial treatment to the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive.

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Overall Survival Time	9.8 months Interval 6.77 to 13.0

SECONDARY outcome

Timeframe: Survival time up to 2 years or date of death

This is defined as the time from commencement of trial treatment to the date of the subsequent CT scan when progressive disease is first confirmed or date of death without previously recorded progression. This outcome is calculated and reported separately for patients who achieve an Objective Response (OR) or Stable Disease (SD). Patients experiencing OR or SD who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Duration of Objective Response	14.6 months Interval 12.1 to The upper estimate of the confidence interval was not attained as there was an insufficient number of participants with events

SECONDARY outcome

Timeframe: Survival time up to 2 years or date of death

This is defined as the time from commencement of trial treatment to the date of the subsequent CT scan when progressive disease is first confirmed or date of death without previously recorded progression. This outcome is calculated and reported separately for patients who achieve an Objective Response (OR) or Stable Disease (SD). Patients experiencing OR or SD who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.

Outcome measures

Measure	Pembrolizumab n=60 Participants Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Duration of Stable Disease	4.39 months Interval 3.97 to 6.77

Adverse Events

Pembrolizumab

Serious events: 51 serious events

Other events: 58 other events

Deaths: 48 deaths

Serious adverse events

Measure	Pembrolizumab n=60 participants at risk Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 10/60 • Number of events 15 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Death	11.7% 7/60 • Number of events 7 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Back pain	5.0% 3/60 • Number of events 5 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Diarrhea	6.7% 4/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other - Death	6.7% 4/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Anorexia	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Fever	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Lung infection	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Psychiatric disorders Confusion	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hypercalcemia	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Stroke	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Ear and labyrinth disorders Vestibular disorder	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Acute kidney injury	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Endocrine disorders Adrenal insufficiency	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Alanine aminotransferase increased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Ataxia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Atrial fibrillation	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Cardiac arrest	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Other - Death	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Dizziness	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Dysphasia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Flank pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Hepatobiliary disorders Other - Hepatobiliary disorders	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hypokalemia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Vascular disorders Hypotension	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Chest Infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Pneumonia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Mucositis oral	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other - Malignant neoplasm	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Vascular disorders Superior vena cava syndrome	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Urinary tract infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Vomiting	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Haemoptysis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Seizure	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Respiratory distress	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders	11.7% 7/60 • Number of events 7 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Shortness of Breath	3.3% 2/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Shortness of Breath	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Lung infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Other - Acute Kidney Injury	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Other - Nervous System	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.

Other adverse events

Measure	Pembrolizumab n=60 participants at risk Pembrolizumab: 200 mg Q3W, intravenous administration for a maximum of 2 years, or until progression or unacceptable toxicity.
Blood and lymphatic system disorders Other - Creatinine decreased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Blood and lymphatic system disorders Other - Haemoptysis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Blood and lymphatic system disorders Other - Hypercalcemia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Blood and lymphatic system disorders Other - Thrombocytopenia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Blood and lymphatic system disorders Anemia	8.3% 5/60 • Number of events 8 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Cardiac arrest	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Other - Ejection systolic murmor	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Heart failure	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Myocardial infarction	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Palpitations	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Sinus bradycardia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Cardiac disorders Atrial fibrillation	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Ear and labyrinth disorders Other - Hearing reduction	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Ear and labyrinth disorders Vestibular disorder	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Endocrine disorders Other - Adrenal insufficiency	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Endocrine disorders Hypophysitis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Endocrine disorders Adrenal insufficiency	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Endocrine disorders Hyperthyroidism	3.3% 2/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Endocrine disorders Hypothyroidism	13.3% 8/60 • Number of events 9 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Eye disorders Other - Age related reduced visual acuity	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Eye disorders Other - Thromboembolic event left eye	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Eye disorders Watering eyes	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Colitis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Dry mouth	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Other - Altered taste	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Other - Decreased appetite	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Other - Gastric reflux	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Other - Reflux	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Mucositis oral	1.7% 1/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Dyspepsia	3.3% 2/60 • Number of events 5 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Dysphagia	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Abdominal pain	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Diarrhea	23.3% 14/60 • Number of events 21 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Vomiting	23.3% 14/60 • Number of events 20 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Constipation	25.0% 15/60 • Number of events 24 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Gastrointestinal disorders Nausea	25.0% 15/60 • Number of events 21 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Chills	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Flu like symptoms	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Abdominal pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Chest wall discomfort (occasional)	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Cough	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Dehydration	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Edema feet	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Hair thinning	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Head cold	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Itch	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Leg cramps	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Poor appetite	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Raised sputum viscosity	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Sore throat	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Swollen feet and ankles	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Other - Weight loss	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Infusion related reaction	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Non-cardiac chest pain	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Malaise	8.3% 5/60 • Number of events 6 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Edema limbs	11.7% 7/60 • Number of events 8 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Fever	15.0% 9/60 • Number of events 11 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Pain	15.0% 9/60 • Number of events 10 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
General disorders Fatigue	60.0% 36/60 • Number of events 62 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Hepatobiliary disorders Other - Bilirubin increased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Hepatobiliary disorders Other - Drug induced liver injury	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Hepatobiliary disorders Other - Raised alk phosphate	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Immune system disorders Other - Rash	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Bronchial infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Chest infections	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Chest Sepsis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Cystitis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Genital candida	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Infected picc line	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Lower respiratory track infection	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Lower respiratory tract infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Oral candida	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Oral candidiasis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Picc line infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Presumed uti	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Thrush	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Undefined infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Unwell	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Viral infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Viral infection around mouth	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Papulopustular rash	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Oral thrush	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Skin infection	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Other - Chest infection	10.0% 6/60 • Number of events 11 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Upper respiratory infection	10.0% 6/60 • Number of events 7 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Lung infection	16.7% 10/60 • Number of events 12 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Infections and infestations Urinary tract infection	16.7% 10/60 • Number of events 16 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Injury, poisoning and procedural complications Bruising	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Injury, poisoning and procedural complications Fall	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Activated partial thromboplastin time prolonged	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Aspartate aminotransferase increased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Blood bilirubin increased	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Blood corticotrophin decreased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations GGT increased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Other - Cortisol low	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Other - Hyperbilirubinemia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Other - Ldh raised - 794 (uln 480)	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Other - Thyroid stimulating hormone increased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Lymphocyte count decreased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Serum amylase increased	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Alanine aminotransferase increased	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Creatinine increased	5.0% 3/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Investigations Weight loss	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hypercalcemia	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hypoalbuminemia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hypocalcemia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Other - Low b12	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Obesity	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Dehydration	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hyperglycemia	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hypokalemia	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hypomagnesemia	10.0% 6/60 • Number of events 9 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Hyponatremia	10.0% 6/60 • Number of events 12 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Metabolism and nutrition disorders Anorexia	33.3% 20/60 • Number of events 28 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Bruising to left arm (garden gate hit it)	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Discitis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Generalised muscle weakness	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Generalized muscle weakness	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Heavy and painful left calf	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Joint pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Left arm pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Left hip/ pelvic pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Left sided gluteal pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Leg ache	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Muscle pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Muscle spasms	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Right hand weakness	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Osteoporosis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Arthralgia	3.3% 2/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Flank pain	3.3% 2/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Knee pain	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Other - Left shoulder pain	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Myalgia	3.3% 2/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Neck pain	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Musculoskeletal and connective tissue disorders Back pain	23.3% 14/60 • Number of events 25 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other - Death	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Ataxia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Concentration impairment	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Dysphasia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Memory impairment	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Other - Involuntary neck movements	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Other - Pins & needles in right arm during antibiotic infusion	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Other - Tingling in extremeties	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Nystagmus	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Seizure	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Stroke	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Tremor	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Lethargy	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Paresthesia	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Peripheral sensory neuropathy	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Headache	8.3% 5/60 • Number of events 6 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Nervous system disorders Dizziness	10.0% 6/60 • Number of events 9 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Psychiatric disorders Confusion	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Psychiatric disorders Depression	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Psychiatric disorders Insomnia	6.7% 4/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Cystitis noninfective	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Proteinuria	1.7% 1/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Other - Raised creatinine	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Other - Renal failure	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Other - Urinary infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Other - Worsening of renal function	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Urinary frequency	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Chronic kidney disease	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Renal and urinary disorders Acute kidney injury	6.7% 4/60 • Number of events 6 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Hoarseness	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Bronchitis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Cap-community acquired pneumonia	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Chest pain	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Exacerbation of copd	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Increased sputum-brown	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Lower respiratory track infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Lower respiratory tract infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Lung crackles	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Mucositis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Reduced air entry and a few creps	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Reduced air entry to right lung	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Reduced air entry to the right lower lobe	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Reduced breath sounds left upper lobe	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Respiratory distress	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Respiratory infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Right basal chest infection	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Scattered creps	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Shortness of breath	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Shortness of breath on minimal exertion	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - White phlegm	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Sore throat	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Chest infection	3.3% 2/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	5.0% 3/60 • Number of events 5 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Exacerbation of chronic obstructive pulmonary disease	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Pneumonia	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.7% 4/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Other - Haemoptysis	6.7% 4/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	8.3% 5/60 • Number of events 5 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Cough	35.0% 21/60 • Number of events 31 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	48.3% 29/60 • Number of events 48 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Abdominal rash	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Blisters on hands	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Dry skin	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Dry skin on legs	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Dry skin under right eye	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Fungal skin rash	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Infected sebaceous cycst	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Itch	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Itch skin	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Itching	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Itchy face	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Itchy skin	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Papulopustular	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Pitting oedema	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Pressure ulcer	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Psoriasis rash	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Rash on legs	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Rash on the legs and arms	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Red legs and mild oedema	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Skin lesion to scalp	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Sore feet and toes	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Sore naval	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Ulcer on left foot	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - X2 sore spots to upper right chest	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Skin ulceration	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Rash acneiform	3.3% 2/60 • Number of events 5 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Skin rash	3.3% 2/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Pruritus	5.0% 3/60 • Number of events 5 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Other - Rash	5.0% 3/60 • Number of events 5 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Dry skin	10.0% 6/60 • Number of events 7 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	20.0% 12/60 • Number of events 14 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Vascular disorders Hypertension	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Vascular disorders Superior vena cava syndrome	1.7% 1/60 • Number of events 2 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Vascular disorders Vasculitis	1.7% 1/60 • Number of events 1 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Vascular disorders Hypotension	5.0% 3/60 • Number of events 3 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.
Vascular disorders Thromboembolic event	5.0% 3/60 • Number of events 4 • Date of patient registration until 6 months after the administration of the last treatment (a maximum of 2 years treatment and 6 months followup after end of treatment) All medical occurrences which met the Adverse Event (AE) definition were reported including abnormal laboratory findings deemed clinically significant by Investigators (abnormal laboratory findings not clinically significant are not AEs) or any pre-existing AEs that worsened by at least 1 CTCAE grade from baseline. SAE expectedness was decided independently using the Reference Safety Information. 2/62 patients were excluded from the Analysis Population as they did not commence trial treatment.

Additional Information

PePS2 Trial Coordinator

Cancer Research UK Clincial Trials Unit, University of Birmingham

Phone: 0121 414 8040

Email: peps2@trials.bham.ac.uk

Results disclosure agreements

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