Trial Outcomes & Findings for Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START) (NCT NCT00409188)

Last Updated: 2015-11-20

Results Overview

Overall survival time was defined as the time from randomization to death. Participants without events were censored at the last date they were known to be alive or the clinical cut-off date, whatever was earlier.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1513 participants

Primary outcome timeframe

Up to 66 months

Results posted on

2015-11-20

Participant Flow

First/last participant (informed consent): 25 January 2007/31 October 2011. Data cut-off for primary endpoint analysis: 08 August 2012. Participants randomized at 264 centers in 33 countries worldwide.

A total of 1908 participants were screened for eligibility and 1513 participants were enrolled and randomized.

Participant milestones

Participant milestones
Measure	Tecemotide (L-BLP25) + Cyclophosphamide A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
Overall Study STARTED	1006	507
Overall Study COMPLETED	623	332
Overall Study NOT COMPLETED	383	175

Reasons for withdrawal

Reasons for withdrawal
Measure	Tecemotide (L-BLP25) + Cyclophosphamide A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
Overall Study Ongoing at data cut-off	383	175

Baseline Characteristics

Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=1006 Participants A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo n=507 Participants A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.	Total n=1513 Participants Total of all reporting groups
Age, Continuous	60.7 years STANDARD_DEVIATION 9.1 • n=5 Participants	60.9 years STANDARD_DEVIATION 9.0 • n=7 Participants	60.8 years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	315 Participants n=5 Participants	162 Participants n=7 Participants	477 Participants n=5 Participants
Sex: Female, Male Male	691 Participants n=5 Participants	345 Participants n=7 Participants	1036 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 66 months

Population: Primary analysis set (modified intention-to-treat \[ITT\] population) was based on the ITT population but prospectively excluded all participants (274 participants) that were randomized during the 6 months (22 Sep 2009 to 22 Mar 2010) prior to the effective date of clinical hold.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=829 Participants A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo n=410 Participants A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
Overall Survival	25.6 months Interval 22.5 to 29.2	22.3 months Interval 19.6 to 25.5

SECONDARY outcome

Timeframe: Up to 66 months

Population: Primary analysis set (modified ITT population) was based on the ITT population but prospectively excluded all participants (274 participants) that were randomized during the 6 months (22 Sep 2009 to 22 Mar 2010) prior to the effective date of clinical hold. "N" signifies the number of participants who were evaluable for this outcome measure.

Time to symptom progression (TTSP) was measured by LCSS. Symptomatic progression was defined as an increase (worsening) of the Average Symptomatic Burden Index (ASBI that is, the mean of the six major lung cancer specific symptom scores of the LCSS patient scale - ranging from 0 to 100 where higher score indicates worst outcome). Worsening was defined as a 10% increase in the scale breadth from the baseline score. TTSP is defined as the time from randomization to worsening in ASBI. Participants without event are censored at the date of the last LCSS assessment.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=829 Participants A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo n=409 Participants A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
Time To Symptom Progression (TTSP) as Measured by the Lung Cancer Symptom Scale (LCSS)	14.2 months Interval 12.9 to 15.7	11.4 months Interval 9.3 to 13.1

SECONDARY outcome

Timeframe: Up to 66 months

Time from randomization to disease progression. Disease progression was defined based on Response Evaluation Criteria in Solid Tumors Version 1.0 \[RECIST v1.0\]) 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.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=829 Participants A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo n=410 Participants A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
Time To Progression (TTP)	10.0 months Interval 9.1 to 11.5	8.4 months Interval 7.2 to 10.8

SECONDARY outcome

Timeframe: Years 1, 2, and 3

The percentages of participants who were alive at 1, 2, and 3 years were calculated as a cumulative percentage by Kaplan-Meier survival analysis approach.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=829 Participants A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo n=410 Participants A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
One-, Two- and Three-year Survival Rate Year 1	77.0 percentage of participants	74.7 percentage of participants
One-, Two- and Three-year Survival Rate Year 2	50.8 percentage of participants	45.9 percentage of participants
One-, Two- and Three-year Survival Rate Year 3	40.2 percentage of participants	37.0 percentage of participants

SECONDARY outcome

Timeframe: From first dose up to 42 days after the last dose of the trial treatment

Population: Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).

Treatment -emergent adverse events were defined as those with onset or worsening occurring at or after the first dosing day of study medication and up to 42 days after the last administration of any study drug or the clinical cut-off date. Injection site reactions were reported as assessed by the Investigator.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=1024 Participants A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo n=477 Participants A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
Number of Participants With Treatment Emergent Adverse Events and Injection Site Reactions Treatment Emergent Adverse events	938 participants	432 participants
Number of Participants With Treatment Emergent Adverse Events and Injection Site Reactions Injection site reaction	176 participants	56 participants

Adverse Events

Tecemotide (L-BLP25) + Cyclophosphamide

Serious events: 303 serious events

Other events: 918 other events

Deaths: 0 deaths

Saline + Placebo

Serious events: 151 serious events

Other events: 417 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study, an integrated clinical and statistical study report shall be written by the Sponsor in consultation with the Coordinating Investigator based on the protocol. The first publication will be a full publication of all data from all sites. The Sponsor is entitled to delay publication in order to obtain patent protection. The ICMJE criteria for authorship will be followed. A separate publication plan will be set up to describe further publications.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=1024 participants at risk A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression was documented.	Saline + Placebo n=477 participants at risk A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 consecutive weekly subcutaneous vaccinations with placebo at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at Week 13, until disease progression was documented.
Gastrointestinal disorders Constipation	7.3% 75/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	5.5% 26/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Gastrointestinal disorders Diarrhoea	8.3% 85/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	9.6% 46/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Gastrointestinal disorders Nausea	13.7% 140/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	8.2% 39/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Gastrointestinal disorders Vomiting	6.3% 65/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	5.5% 26/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
General disorders Asthenia	6.9% 71/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	6.1% 29/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
General disorders Chest pain	12.7% 130/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	9.0% 43/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
General disorders Fatigue	19.0% 195/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	21.4% 102/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
General disorders Influenza like illness	4.4% 45/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	5.7% 27/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
General disorders Non-cardiac chest pain	5.6% 57/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	5.0% 24/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
General disorders Pyrexia	7.8% 80/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	8.6% 41/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Infections and infestations Bronchitis	8.1% 83/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	8.0% 38/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Infections and infestations Nasopharyngitis	12.5% 128/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	9.2% 44/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Infections and infestations Upper respiratory tract infection	9.4% 96/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	7.8% 37/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Injury, poisoning and procedural complications Radiation pneumonitis	7.5% 77/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	6.3% 30/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Metabolism and nutrition disorders Decreased appetite	10.6% 109/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	9.2% 44/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Musculoskeletal and connective tissue disorders Arthralgia	10.5% 108/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	6.9% 33/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Musculoskeletal and connective tissue disorders Back pain	14.3% 146/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	10.9% 52/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.3% 54/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	4.6% 22/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.0% 92/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	6.9% 33/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Musculoskeletal and connective tissue disorders Myalgia	7.1% 73/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	3.8% 18/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 69/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	6.1% 29/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Nervous system disorders Dizziness	8.5% 87/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	7.8% 37/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Nervous system disorders Headache	12.0% 123/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	11.3% 54/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Psychiatric disorders Insomnia	6.2% 64/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	5.2% 25/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Respiratory, thoracic and mediastinal disorders Cough	32.8% 336/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	27.9% 133/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.0% 225/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	21.6% 103/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.9% 60/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	6.7% 32/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Skin and subcutaneous tissue disorders Rash	5.2% 53/1024 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).	5.7% 27/477 • Up to 66 months Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).