Trial Outcomes & Findings for Cancer Vaccine Study for Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) in the Asian Population (NCT NCT01015443)

Last Updated: 2016-10-26

Results Overview

OS time was measured as the time (in months) between the date of randomization and the date of death. For subjects alive or lost to follow-up at time of analysis, the time between the date of randomization and the date on which the subject was last known alive was calculated and used as a censored observation in the analysis.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

285 participants

Primary outcome timeframe

From the date of randomization until death, assessed up to 5.6 years

Results posted on

2016-10-26

Participant Flow

First/last subject (informed consent): 03 Dec 2009/10-Sep-2014. Data cut-off date: June 2015; Subjects were randomized at 45 centers in 5 countries worldwide.

A total of 350 subjects were screened for eligibility and 285 subjects were enrolled and randomized.

Participant milestones

Participant milestones
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+Best Supportive Care A single intravenous (IV) infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 microgram (mcg) and then at 6-Week interval, beginning at Week 14 (maintenance phase) until disease progression (PD) is documented or the subject discontinued for any other reason. The best supportive care (BSC) was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC A single IV infusion of 0.9 percent (%) sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Overall Study STARTED	191	94
Overall Study Treated	191	93
Overall Study COMPLETED	191	94
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cancer Vaccine Study for Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) in the Asian Population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=191 Participants A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=94 Participants A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Total n=285 Participants Total of all reporting groups
Age, Continuous	56.5 Years STANDARD_DEVIATION 8.93 • n=93 Participants	59.3 Years STANDARD_DEVIATION 9.08 • n=4 Participants	57.4 Years STANDARD_DEVIATION 9.06 • n=27 Participants
Sex: Female, Male Female	31 Participants n=93 Participants	18 Participants n=4 Participants	49 Participants n=27 Participants
Sex: Female, Male Male	160 Participants n=93 Participants	76 Participants n=4 Participants	236 Participants n=27 Participants

PRIMARY outcome

Timeframe: From the date of randomization until death, assessed up to 5.6 years

Population: The modified intent-to-treat (mITT) analysis set was based on the intention-to-treat (ITT) analysis set (ITT analysis set included all the subjects randomized into the study), but included only subjects with concurrent primary chemo-radiotherapy and prospectively excluded the 5 subjects who were randomized prior to the clinical hold.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=135 Participants A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=68 Participants A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Overall Survival (OS) Time	NA Months Interval 28.7 to Fewer subjects were randomized than planned and analysis was performed earlier than planned due to termination of the tecemotide (L-BLP25) program which resulted in few events. Hence, median and upper limit of confidence interval were not estimable.	NA Months Interval 23.7 to Fewer subjects were randomized than planned and analysis was performed earlier than planned due to termination of the tecemotide (L-BLP25) program which resulted in few events. Hence, median and upper limit of confidence interval were not estimable.

SECONDARY outcome

Timeframe: From the date of randomization to the date of symptomatic progression, assessed up to 5.6 years

Population: The mITT analysis set was based on the ITT analysis set (ITT analysis set included all the subjects randomized into the study), but included only subjects with concurrent primary chemo-radiotherapy and prospectively excluded the 5 subjects who were randomized prior to the clinical hold.

TTSP was measured from randomization to symptomatic progression by lung cancer symptom scale (LCSS) used to measure symptom changes relevant to quality of life (QoL).It consisted of 9 items focused on cancer symptoms (loss of appetite, fatigue, cough, shortness of breath, blood in sputum, pain, symptoms of cancer, illness affecting normal activity, QoL).For each symptom score distance from left boundary to point where subject has marked line was measured in millimeters (mm).Total scale length was 100 mm. Symptomatic progression was defined as increase/worsening of average symptomatic burden index (ASBI) (mean of 6 major lung cancer specific symptom scores);Worsening defined as 10% increase of scale breadth from baseline. Score 0 indicate no/minimum symptoms;100 indicates maximum level of symptoms. Subjects without symptomatic progression/lost to follow-up at time of analysis: time from date of randomization to date of last LCSS assessment was calculated \& used as censored observation.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=135 Participants A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=68 Participants A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Time to Symptom Progression (TTSP)	19.3 Months Interval 16.7 to Fewer subjects were randomized than planned and analysis was performed earlier than planned due to termination of the tecemotide (L-BLP25) program which resulted in few events. Hence, upper limit of confidence interval was not estimable.	24.2 Months Interval 10.8 to Fewer subjects were randomized than planned and analysis was performed earlier than planned due to termination of the tecemotide (L-BLP25) program which resulted in few events. Hence, upper limit of confidence interval was not estimable.

SECONDARY outcome

Timeframe: From the date of randomization to the date of radiological confirmation of PD, assessed up to 5.6 years

Time from randomization to radiological confirmation of disease progression (PD) as determined by the investigator. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions from nadir, or the appearance of one or more new lesions as per RECIST version 1.0. For subjects without radiological confirmed PD who discontinued or died due to PD, the date of trial treatment discontinuation was used as event date. Subjects who missed 2 consecutive scheduled doses without evaluable assessment for the related visits and who were lost to follow-up thereafter were considered as having PD, TTP was calculated from the date of randomization to the date of their first missed treatment. Subjects without PD at time of analysis are censored at either date of last vaccination or death or discontinuation of treatment or lost to follow-up.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=135 Participants A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=68 Participants A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Time to Progression (TTP)	6.4 Months Interval 5.5 to 8.6	7.5 Months Interval 5.9 to 15.2

SECONDARY outcome

Timeframe: From the date of randomization to PD, assessed up to 5.6 years

Time from randomization to objective disease progression (PD) as determined by the investigator or death. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions from nadir, or the appearance of one or more new lesions as per RECIST version 1.0. Subjects who missed 2 consecutive scheduled doses without evaluable assessment for the related visits and who were lost to follow-up thereafter were considered as having PD, and the PFS was calculated from the date of randomization to the date of their first missed treatment. PFS time for subjects without an event was censored as of the date of last performed imaging.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=135 Participants A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=68 Participants A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Progression Free Survival (PFS)	7.0 Months Interval 5.5 to 8.7	8.7 Months Interval 5.9 to 15.2

SECONDARY outcome

Timeframe: From the date of randomization to the date of first missed treatment, assessed up to 5.6 years

TTF was time from randomization to discontinuation of trial treatment for any reason as reported by the investigator. For subjects still receiving treatment at the time of analysis, the time between the date of randomization and the last date of treatment will be used as a censored observation in the analysis. Subjects who missed 2 consecutive scheduled doses without evaluable assessment for the related visits and who were lost to follow-up thereafter were considered treatment failure and the TTF was calculated from the date of randomization to the date of their first missed treatment.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=135 Participants A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=68 Participants A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Time to Treatment Failure (TTF)	4.6 Months Interval 4.5 to 6.0	4.6 Months Interval 3.3 to 5.9

SECONDARY outcome

Timeframe: From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years

Population: Safety analysis set included all subjects who received at least one dose of trial treatment.

An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occur between first dose of study drug administration and 42 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with TEAE leading to death and permanent discontinuation of any trial treatment were presented.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=191 Participants A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=93 Participants A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs leading to discontinuation	22 Subjects	11 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death Serious TEAE	34 Subjects	21 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs leading to death	4 Subjects	2 Subjects
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death TEAEs	156 Subjects	73 Subjects

Adverse Events

Tecemotide (L-BLP25)+Cyclophosphamide+BSC

Serious events: 34 serious events

Other events: 151 other events

Deaths: 0 deaths

Saline + Placebo + BSC

Serious events: 21 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Tecemotide (L-BLP25)+Cyclophosphamide+BSC n=191 participants at risk A single IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of low dose cyclophosphamide was given 3 days prior to first tecemotide (L-BLP25) vaccination. After receiving single low dose cyclophosphamide, subjects received 8 consecutive weekly (Week 1, 2, 3, 4, 5, 6, 7, and 8 primary treatment phase) subcutaneous tecemotide (L-BLP25) vaccinations at a dose of 918 mcg and then at 6-Week interval, beginning at Week 14 (maintenance phase) until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.	Saline + Placebo + BSC n=93 participants at risk A single IV infusion of 0.9% sodium chloride (saline) was administered 3 days prior to first placebo vaccination. After receiving saline solution, subjects received 8 consecutive weekly subcutaneous vaccinations with placebo at Week 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance treatment at 6-Week intervals, beginning at Week 14, until PD is documented or the subject discontinued for any other reason. The BSC was provided as per the investigator's discretion and was not limited to palliative radiation, psychosocial support, analgesics and nutritional support.
Gastrointestinal disorders Abdominal pain upper	3.1% 6/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	5.4% 5/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Gastrointestinal disorders Constipation	2.6% 5/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	8.6% 8/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Gastrointestinal disorders Diarrhoea	3.7% 7/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	5.4% 5/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
General disorders Chest discomfort	2.6% 5/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	6.5% 6/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
General disorders Disease progression	5.8% 11/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	3.2% 3/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
General disorders Fatigue	12.6% 24/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	14.0% 13/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
General disorders Non-cardiac chest pain	7.9% 15/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	11.8% 11/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
General disorders Oedema peripheral	2.6% 5/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	5.4% 5/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
General disorders Pyrexia	5.8% 11/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	11.8% 11/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Infections and infestations Upper respiratory tract infection	7.9% 15/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	7.5% 7/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Injury, poisoning and procedural complications Radiation pneumonitis	4.2% 8/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	6.5% 6/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Metabolism and nutrition disorders Decreased appetite	10.5% 20/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	7.5% 7/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Metabolism and nutrition disorders Hyperuricaemia	0.52% 1/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	5.4% 5/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Musculoskeletal and connective tissue disorders Arthralgia	3.1% 6/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	9.7% 9/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Musculoskeletal and connective tissue disorders Back pain	5.2% 10/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	9.7% 9/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.2% 8/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	5.4% 5/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Nervous system disorders Dizziness	8.4% 16/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	4.3% 4/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Respiratory, thoracic and mediastinal disorders Cough	24.6% 47/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	17.2% 16/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.4% 18/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	16.1% 15/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.8% 11/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	4.3% 4/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	5.2% 10/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	3.2% 3/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.
Skin and subcutaneous tissue disorders Rash	6.8% 13/191 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.	2.2% 2/93 • From the first dose of study drug administration until 42 days after the last dose of study drug administration, assessed up to 5.6 years Safety analysis set included all subjects who received at least one dose of trial treatment.