Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) in Sequential Combination With Gemcitabine as First Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer (NCT NCT00940875)

NCT ID: NCT00940875

Last Updated: 2015-04-02

Results Overview

Progression-free survival (PFS) was defined as the time from randomization to the date of first documentation of progressive disease (PD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.0, or date of death from any cause. PD was defined for target lesions (TLs) as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment, and for non-target lesions (NTLs) as unequivocal progression of NTLs. Participants without documented PD were censored at the date of last tumor assessment, the last date recorded in the drug log, or the last date of follow-up the participant was known to be progression free, whichever was last. Participants without a post-Baseline (BL) tumor assessment who were known to be alive were censored at the date of randomization.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 54 participants
• Primary outcome timeframe: BL, Day 22 of Cycles 2, 4, and 6 (28-day cycles), every 2 months thereafter until disease progression, participant withdrawal, or study termination (12 months after randomization of the last participant).
• Results posted on: 2015-04-02

Participant Flow

Participant milestones

Measure	Gemcitabine Monotherapy Participants received gemcitabine, 1000 milligrams per square meter (mg/m\^2), intravenously (IV), on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine (G) Plus (+) Erlotinib (E) Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, orally (PO), once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Treatment Phase STARTED	31	23
Treatment Phase COMPLETED	5	4
Treatment Phase NOT COMPLETED	26	19
Post-Study Treatment STARTED	0	4
Post-Study Treatment COMPLETED	0	1
Post-Study Treatment NOT COMPLETED	0	3

Reasons for withdrawal

Measure	Gemcitabine Monotherapy Participants received gemcitabine, 1000 milligrams per square meter (mg/m\^2), intravenously (IV), on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine (G) Plus (+) Erlotinib (E) Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, orally (PO), once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Treatment Phase Adverse Event	9	3
Treatment Phase Death	3	5
Treatment Phase Lack of Efficacy	1	0
Treatment Phase Withdrawal by Subject	3	0
Treatment Phase Disease progression	9	11
Treatment Phase Physician Decision	1	0
Post-Study Treatment Death	0	1
Post-Study Treatment Disease Progression	0	2

Baseline Characteristics

A Study of Tarceva (Erlotinib) in Sequential Combination With Gemcitabine as First Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Gemcitabine Monotherapy n=28 Participants Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=26 Participants Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).	Total n=54 Participants Total of all reporting groups
Age, Continuous	74.8 years STANDARD_DEVIATION 8.72 • n=5 Participants	72.8 years STANDARD_DEVIATION 7.91 • n=7 Participants	73.8 years STANDARD_DEVIATION 8.32 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: BL, Day 22 of Cycles 2, 4, and 6 (28-day cycles), every 2 months thereafter until disease progression, participant withdrawal, or study termination (12 months after randomization of the last participant).

Population: FAS

Progression-free survival (PFS) was defined as the time from randomization to the date of first documentation of progressive disease (PD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.0, or date of death from any cause. PD was defined for target lesions (TLs) as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment, and for non-target lesions (NTLs) as unequivocal progression of NTLs. Participants without documented PD were censored at the date of last tumor assessment, the last date recorded in the drug log, or the last date of follow-up the participant was known to be progression free, whichever was last. Participants without a post-Baseline (BL) tumor assessment who were known to be alive were censored at the date of randomization.

Outcome measures

Measure	Gemcitabine Monotherapy n=28 Participants Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=26 Participants Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Percentage of Participants With Disease Progression or Death	96.4 percentage of participants	96.2 percentage of participants

PRIMARY outcome

Timeframe: BL, Day 22 of Cycles 2, 4, and 6 (28-day cycles), every 2 months thereafter until disease progression, participant withdrawal, or study termination (up to 2 years)

Population: FAS

The median time, in weeks, between randomization and PFS event. Participants without documented PD were censored at the date of last tumor assessment, the last date recorded in the drug log, or the last date of follow-up the participant was known to be progression free, whichever was last. Participants without a post-BL tumor assessment who were known to be alive were censored at the date of randomization. PFS was estimated by using Kaplan-Meier methodology.

Outcome measures

Measure	Gemcitabine Monotherapy n=28 Participants Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=26 Participants Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
PFS	8.0 weeks Interval 7.0 to 21.0	10.3 weeks Interval 7.0 to 15.0

SECONDARY outcome

Timeframe: BL, Day 22 of Cycle 2, 4, and 6 (28-day cycles), every 2 months thereafter until disease progression, participant withdrawal, or study termination (12 months after randomization of the last participant).

Population: FAS

As per RECIST V 1.0: for TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of TLs taking as reference the BL SLD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% confidence interval (CI) for one-sample binomial was determined using the Pearson-Clopper Method.

Outcome measures

Measure	Gemcitabine Monotherapy n=28 Participants Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=26 Participants Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Percentage of Participants Who Achieved Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST V 1.0	7.1 percentage of participants Interval 0.9 to 23.5	3.8 percentage of participants Interval 0.1 to 19.6

SECONDARY outcome

Timeframe: Weeks 8 and 16

Population: FAS

Non-progression was defined as CR, PR, or stable disease according to RECIST V 1.0: for TLs, CR was defined as the disappearance of all TLs, PR was defined as at least a 30% decrease in the SLD of TLs taking as reference the BL SLD, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD recorded since the start of treatment. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels, and SD was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above the normal limits. The 95% CI for one-sample binomial was determined using the Pearson-Clopper method.

Outcome measures

Measure	Gemcitabine Monotherapy n=28 Participants Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=26 Participants Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Percentage of Participants With Non-Progression at Weeks 8 and 16 Week 8	50.0 percentage of participants Interval 30.6 to 69.4	38.5 percentage of participants Interval 20.2 to 59.4
Percentage of Participants With Non-Progression at Weeks 8 and 16 Week 16	25.0 percentage of participants Interval 10.7 to 44.9	11.5 percentage of participants Interval 2.4 to 30.2

SECONDARY outcome

Timeframe: BL, Days 1, 8, and 15 of Cycles 1-6 (28-day cycles), every 28 days thereafter until death, participant withdrawal, or study termination up to 2 years.

Population: FAS

Outcome measures

Measure	Gemcitabine Monotherapy n=28 Participants Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=26 Participants Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Percentage of Participants Who Died	92.9 percentage of participants	76.9 percentage of participants

SECONDARY outcome

Timeframe: BL, Days 1, 8, and 15 of Cycles 1-6 (28-day cycles), every 28 days thereafter until death, participant withdrawal, or study termination up to 2 years.

Population: FAS

OS was defined as the median time, in weeks, between randomization and death due to any cause. Participants without documented death were censored at the last date recorded in the drug log, or the last date of follow-up the participant was known to be alive, whichever was last. Participants without a post-BL assessment who were known to be alive were censored at the date of randomization. OS was estimated using Kaplan-Meier methodology.

Outcome measures

Measure	Gemcitabine Monotherapy n=28 Participants Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=26 Participants Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Overall Survival (OS)	21.3 weeks Interval 13.0 to 40.0	17.1 weeks Interval 11.0 to 37.0

SECONDARY outcome

Timeframe: BL, Days 1, 8, and 15 of Cycles 1-6 (28-day cycles), every 28 days thereafter until death, participant withdrawal, or study termination up to 2 years.

Population: Data could not be summarized to be included in the data table because there are too few events to calculate a median and confidence intervals.

Duration of response was defined as the time between the first documentation of CR or PR (whichever status was recorded first as assessed by the RECIST V 1.0) until the date of documented disease progression or death. Participants with no documented disease progression or death after confirmed CR or PR were censored at the date of the last tumor assessment or last date of follow-up when the participant was known to be progression free, whichever was last.

Outcome measures

Outcome data not reported

Adverse Events

Gemcitabine Monotherapy

Serious events: 20 serious events

Other events: 28 other events

Deaths: 0 deaths

Gemcitabine + Erlotinib

Serious events: 14 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Gemcitabine Monotherapy n=31 participants at risk Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=23 participants at risk Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmomary embolism	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Respiratory distress	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Lower respiratory tract infection	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Pneumonia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Cellulitis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Herpes zoster	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Lung infection	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Otitis externa	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Sepsis	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Septic shock	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Pyrexia	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Malaise	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Sudden death	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Diarrhoea	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Constipation	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Dehydration	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Cardiac disorders Atrial fibrillation	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Cardiac disorders Atrial flutter	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Cardiac disorders Cardiac failure congestive	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Embolism venous	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Hypotension	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Peripheral embolism	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Anxiety	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Confusional state	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Mood altered	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Anaemia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Haemoglobin decreased	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Troponin increased	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Plantar fasciitis	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Cerebrovascular accident	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Renal and urinary disorders Renal impairment	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.

Other adverse events

Measure	Gemcitabine Monotherapy n=31 participants at risk Participants received gemcitabine, 1000 mg/m\^2, IV, on Days 1, 8, and 15 of Cycles 1-6 (28-day cycles). Participants consented to post-treatment survival follow-up received no further treatment.	Gemcitabine + Erlotinib n=23 participants at risk Participants received gemcitabine, 1250 mg/m\^2, IV, on Days 1 and 8 of Cycles 1-6 (28-day cycles). Participants also received erlotinib, 150 mg tablets, PO, once per day on Days 15-28 of Cycles 1-6 (28-day cycles); and 150 mg tablets, PO, once per day thereafter until disease progression, unacceptable toxicity, withdrawal, or study termination (12 months after randomization of the last participant).
Gastrointestinal disorders Abdominal pain	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Dry mouth	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	21.7% 5/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Dyspepsia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	13.0% 3/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Abdominal pain upper	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Dysphagia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Mouth ulceration	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Stomatitis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Gingival pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Mouth haemorrhage	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Toothache	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Fatigue	22.6% 7/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	43.5% 10/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Oedema peripheral	25.8% 8/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	17.4% 4/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Chest pain	16.1% 5/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	21.7% 5/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Pyrexia	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Mucosal inflammation	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	13.0% 3/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Pain	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Ill-defined disorder	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Influenza like illness	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
General disorders Injection site reaction	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Back pain	16.1% 5/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Arthralgia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	13.0% 3/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	13.0% 3/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	13.0% 3/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Neck pain	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Myalgia	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.6% 7/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	30.4% 7/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Cough	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	13.0% 3/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Productive cough	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonary hilum mass	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Rales	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Respiratory tract haemorrhage	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Sputum retention	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Lower respiratory tract infection	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Oral candidiasis	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Cellulitis	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Lung infection	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Pneumonia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Upper respiratory tract infection	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Sepsis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Clostridium difficile colitis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Furuncle	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Infection	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Paronychia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Infections and infestations Respiratory tract infection	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Rash	16.1% 5/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	65.2% 15/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Dry skin	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	17.4% 4/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Acne	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Decubitus ulcer	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Skin and subcutaneous tissue disorders Skin ulcer	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Cardiac disorders Cardiac failure congestive	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Cardiac disorders Atrial fibrillation	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Cardiac disorders Pericardial effusion	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Injury, poisoning and procedural complications Laceration	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Injury, poisoning and procedural complications Contusion	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Injury, poisoning and procedural complications Fall	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Injury, poisoning and procedural complications Thermal burn	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Ear and labyrinth disorders Deafness	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Dizziness	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Headache	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Lethargy	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Ataxia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Paraesthesia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Depressed level of consciousness	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Dizziness postural	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Dysgeusia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Hemiparesis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Hypoaesthesia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Intention tremor	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Neuropathy peripheral	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Post herpetic neuralgia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Pyramidal tract syndrome	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Syncope	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Tardive dyskinesia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Nervous system disorders Tremor	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Hypotension	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	21.7% 5/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Hypertension	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Ischaemic limb pain	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Thrombophlebitis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Thrombophlebitis superficial	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Vascular disorders Venous thrombosis limb	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Blepharitis	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Dry eye	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Exophthalmos	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Eye irritation	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Eye pain	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Foreign body sensation in eyes	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Uveitis	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Vision blurred	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Eye disorders Visual impairment	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Renal and urinary disorders Pollakiuria	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Renal and urinary disorders Renal impairment	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Renal and urinary disorders Dysuria	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Renal and urinary disorders Haematuria	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Renal and urinary disorders Urinary retention	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Weight decreased	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Alanine aminotransferase increased	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Haemoglobin decreased	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Aspartate aminotransferase increased	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Platelet count decreased	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Blood alkaline phosphatase increased	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Eastern cooperative oncology group performance status worsened	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Gamma-glutamyltransferase increased	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Hepatic enzyme increased	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Liver function test abnormal	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Platelet count increased	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Investigations Weight increased	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Anaemia	19.4% 6/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	30.4% 7/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Neutropenia	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Bone marrow failure	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Febrile neutropenia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Blood and lymphatic system disorders Leukopenia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Decreased appetite	12.9% 4/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Hypokalaemia	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Dehydration	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Hyperkalaemia	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Gout	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Metabolism and nutrition disorders Hypomagnesaemia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Confusional state	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Insomnia	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	13.0% 3/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Anxiety	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	8.7% 2/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Depression	6.5% 2/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Agitation	0.00% 0/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	4.3% 1/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Delirium	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Psychiatric disorders Depressed mood	3.2% 1/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	0.00% 0/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Nausea	41.9% 13/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	56.5% 13/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Diarrhoea	9.7% 3/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	52.2% 12/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Constipation	19.4% 6/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	30.4% 7/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.
Gastrointestinal disorders Vomiting	16.1% 5/31 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.	26.1% 6/23 • Adverse events (AEs) were recorded from BL until 28 days after the last date study treatment was received. All participants who received at least 1 dose/infusion of study treatment and had at least 1 safety assessment performed after BL were included in the safety analysis.

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER