Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Vaccines

Cyclophosphamide

Immunomodulating Agents

Immunologic Factors

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

After receiving a single low-dose cyclophosphamide, participants will receive weekly subcutaneous vaccinations with tecemotide (L-BLP25) (930 microgram \[mcg\]) for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (930 mcg) will be administered every 6 weeks until progressive disease (PD).

Tecemotide (L-BLP25)

A single intravenous (IV) infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg/m\^2) of cyclophosphamide will be administered 3 days prior to tecemotide (L-BLP25), the first vaccine treatment.

Single low dose cyclophosphamide

After receiving single dose of saline, participants will receive weekly subcutaneous vaccinations with placebo that matches with tecemotide (L-BLP25) for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with placebo will be administered every 6 weeks until PD.

Placebo

A single dose of saline (sodium chloride, 9 grams per liter \[g/L\]) will be administered intravenously, 3 days prior to the start of placebo.

Saline

Medical Responsible

This is a phase I/II study in Japan to evaluate the safety of EMD531444 and its effects on survival time in patients with stage III unresectable non-small cell lung cancer.

Phase I part is designed to evaluate the safety of EMD531444 930 microgram (mcg) dose to be used in phase II. Phase II part is designed to be conducted as randomized, double blind, placebo controlled study to compare overall survival time in all randomized subjects.

Study of Tecemotide (L-BLP25) in Participants With Stage III Unresectable Non-small Cell Lung Cancer (NSCLC) Following Primary Chemoradiotherapy

Combined Phase I/II Clinical Study of EMD531444(L-BLP25 or BLP25 Liposome Vaccine) in Subjects With Stage III Unresectable Non-small Cell Lung Cancer Following Primary Chemoradiotherapy

OS time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date (01 May 2014), whichever was earlier.

TTP was defined as the time from date of randomization to date of radiological diagnosis of PD (based on Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.0). In the event that radiological confirmation could not be obtained but participant was withdrawn from trial treatment or died due to disease progression, TTP was measured from date of randomization to the date of discontinuation of trial treatment. Participants without event who died from causes other than disease progression were censored at date of death. Participants without event who were lost to follow-up were censored at the date of lost to follow-up, except if they missed 2 consecutive scheduled doses, in which case they were considered as having disease progression at time of first missed administration. Participants without event with ongoing treatment at time of analysis, or who had stopped treatment for reasons other than PD, were censored on the date of last treatment administration.

PFS time was defined as the duration from randomization to either first observation of objective PD (based on RECIST v1.0) or occurrence of death due to any cause. Participants without event still on treatment at time of analysis, or who stopped treatment for reasons other than PD or PD without radiological confirmed progression, were censored at the last imaging date. Participants without event who were lost to follow-up were censored at the date of lost to follow-up, except if they missed 2 consecutive scheduled doses, in which case they were considered as having disease progression at time of first missed administration.

TTF was defined as the duration from date of randomization to the date of discontinuation of any trial treatment (cyclophosphamide or saline, tecemotide \[L-BLP25\] or placebo vaccine) for any reason as reported by the Investigator. Participants who had missed 2 consecutive scheduled doses and were subsequently lost to follow-up were considered as treatment failures with event date as date of first missed administration. Participants without event still on treatment at time of analysis were censored on the date of last treatment administration.

Merck Serono Co., Ltd., Japan

Merck KGaA, Darmstadt, Germany

Safety analysis set included all subjects who were treated with tecemotide \[L-BLP25\] or placebo. Reported treatment-emergent adverse events included events that emerged during treatment having been absent pre-treatment, or worsened relative to the pre-treatment state.

Single dose of cyclophosphamide (300 milligrams per square meter \[mg/m\^2\] to a maximum of 600 mg) was administered intravenously, 3 days prior to the start of vaccination, followed by weekly subcutaneous vaccinations with tecemotide (L-BLP25) (930 mcg) for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (930 mcg) were administered every 6 weeks until PD was documented.

Tecemotide (L-BLP25) + Cyclophosphamide

Single dose of saline (sodium chloride, 9 grams per liter \[g/L\]) was administered intravenously, 3 days prior to the start of vaccination, followed by weekly subcutaneous vaccinations with placebo doses matched to tecemotide (L-BLP25) for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with placebo were administered every 6 weeks until PD was documented.

Placebo + Saline

Total

Age, Continuous

Sex: Female, Male

Intention to Treat (ITT) analysis set included all subjects randomly allocated to a treatment (tecemotide \[L-BLP25\] or placebo)

Merck KGaA Communication Center

ITT analysis set included all subjects randomly allocated to a treatment (tecemotide \[L-BLP25\] or placebo).

Overall Survival (OS) Time

ITT Analysis Set included all subjects randomly allocated to a treatment (tecemotide \[L-BLP25\] or placebo).

Time To Progression (TTP) - Investigator Read

Progression Free Survival (PFS) Time - Investigator Read

Time to Treatment Failure (TTF)

Single dose of cyclophosphamide (300 milligrams per square meter \[mg/m\^2\] to a maximum of 600 mg) was administered intravenously, 3 days prior to the start of vaccination, followed by weekly subcutaneous vaccinations with tecemotide (L-BLP25) (930 microgram \[mcg\]) for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (930 mcg) were administered every 6 weeks until progressive disease (PD) was documented.

Overall Study

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Smoldering Multiple Myeloma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

After receiving single low dose of cyclophosphamide, subjects will receive 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide (L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy is documented.

After receiving multiple low dose of cyclophosphamide, subjects will receive 8 consecutive weekly subcutaneous vaccinations with 806 mcg of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide (L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy is documented.

An intravenous (IV) infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide will be given 3 days before the first vaccine treatment.

An IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of cyclophosphamide will be given 3 days before the first vaccine treatment plus an intravenous dose of cyclophosphamide (300 mg/m\^2, to a maximum of 600 mg) 3 days prior to the tecemotide (LBLP25) administration at week 5 of the weekly treatment phase and 3 days prior to every tecemotide (L-BLP25) administration during the treatment phase with 6-Weekly administration of tecemotide (L-BLP25), commencing at Week 14 up to a maximum treatment period of 2 years.

Multiple low dose cyclophosphamide

Tecemotide (L-BLP25) is believed to induce a Mucinous glycoprotein 1 (MUC1)-specific T-cell response after vaccination. The primary purpose of this study is to ascertain whether vaccination with tecemotide (L-BLP25) induces a MUC1-specific T-cell response in slowly progressive or chemotherapy naive multiple myeloma subjects.

Study of Tecemotide (L-BLP25) in Subjects With Slowly Progressive Multiple Myeloma With no Symptoms and Who Have Had no Chemotherapy

A Randomized, Open-label, Phase II Study With Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Subjects With Either Chemotherapy-naïve, Slowly Progressive, Asymptomatic Multiple Myeloma or With Stage II/III Multiple Myeloma in Stable Response/Plateau Phase Following Anti-tumor Therapy

The overall immune response was achieved at least for 2 timepoints; that is at least 1 parameter in at least 1 assay (Lymphoproliferation assay, enzyme-linked immunospot (ELISPOT) for interferon \[IFN\] gamma, and intracellular IFN gamma cytokine assay in peripheral blood mononuclear cell \[PBMC\]) with ratio to background \>=2, and ratio of background-corrected value to baseline \>=2;Specific immune response at a given timepoint 't' was considered as differences of log-scale values under stimulation (X vax,t ) to those of the respective unstimulated controls (Xneg,t, background values)were computed after certain assay-specific pre-processing steps: Yt = Xvax,t - Xneg,t; A participant was considered to show positive stimulation-induced immune response at timepoint 't' (POS\[t\]=1), upon fulfilling the following criteria: Yt =\>1 (That is at least a 2-fold higher value under stimulation than without stimulation). AVvax,t-1SEM vax,t \> AVneg,t+1SEMneg,t (ELISPOT and proliferation assay only).

Baseline immune response towards MUC1 was defined as an immune response towards BP25, MUC-A2 or MUC-A11 peptide stimulation which was present in at least one of the two baseline assessments; the specific immune responses at baseline were based on the averaged baseline values across the two baseline visits. Initial increase of MUC1-specific immune response was defined as an increase of MUC1-specific immune response during the primary treatment period (up to Week 9).

Relationship between immune response with HLA subtypes was determined by analyzing the number of participants with overall induced immune response grouped by the presence versus absence of the given HLA type.

OCR (CR, or PR, or MR or NC or PD or NE) was defined per Blade Criteria. OCR rate (CR, or PR, or MR) was defined as the number of participants having experienced at least once a CR, PR, or MR, divided by the number of all participants. CR: negative immunofixation on serum and urine monoclonal paraprotein (M-protein), disappearance of any soft tissue plasmacytomas (STP), \<=5% plasma cells in bone marrow (BM); PR: \>=50% reduction in serum M-protein, plasma cells in BM, size of STP; \>=90% reduction of urinary M-protein in 24 hours, no increase in size/number of the lytic bone lesions (LBL). MR: 25%-49% reduction in serum M-protein, plasma cells in BM aspirate in non-secretory myeloma participants, size of STP; 50%-89% reduction in 24 h urinary light chain reaction (LCR), and no increase in size/number of LBL. PD: \>25% increase in the serum M-protein level, 24 hour urinary LCR. Increase in size of existing BL or STP, development of new BL or STP, or development of hypercalcemia

Progression was defined as follows per Blade criteria: The disease was considered to be progressive if it met 1 or more of the following: \>25% increase in the level of serum monoclonal paraprotein (M-protein);\>25% increase in the 24 h urinary light chain excretion; \>25% increase in plasma cells in the bone marrow- definite increase in the size of existing bone lesions or soft tissues plasmacytomas (STP); Development of new bone lesions or STP, or development of hypercalcemia. TTP was defined as time from randomization to disease progression. Participants without events were censored on the date of last tumor assessment. Participants without PD at time of treatment discontinuation were censored at the date of discontinuation. Participants without PD at the time of the analysis but still on treatment were censored at the date of the latest available multiple myeloma status assessment. Participants dying from causes other than PD were treated as censored observations at time of death.

Time from date of randomization to the date of first anti-tumor therapy since end of study treatment. In case a concomitant or concurrent procedure was identified as anti-tumor therapy during the medical review process, the start date of that anti-tumor therapy was used instead. Participants in the survival follow-up phase without subsequent anti-tumor therapy at the time of the analysis were censored at the latest available follow-up date. Participants without anti-tumor therapy and still on treatment at the time of analysis were censored at the data cut-off date if any trial treatment administration was recorded after the data cut-off date. In case no such record exists, the subject was censored at the last available administration date prior or equal to the data cut-off date. Participants dying before start of subsequent anti-tumor therapy were treated as censored observations at time of death.

TEAEs occurred between the first dose of study drug administration and up to 42 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state. A Serious TEAE 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.Grade 3 and 4 TEAES as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 3 (NCI-CTCAE v3.0) were presented. Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL).Grade 4 refers to Life-threatening consequences; where urgent intervention indicated. Injection site reactions, term used per NCI-CTCAE, were also presented.

Tecemotide (L-BLP25): After receiving single low dose cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 mcg of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide \[L-BLP25\]) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy was documented.

Single low dose cyclophosphamide: An intravenous (IV) infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before the first vaccine treatment.

Tecemotide (L-BLP25) Plus Single Low Dose Cyclophosphamide

Tecemotide (L-BLP25): After receiving multiple low dose cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 mcg of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide(L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy was documented.

Multiple low dose cyclophosphamide: An IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of cyclophosphamide was given 3 days before the first vaccine treatment plus an IV dose of cyclophosphamide (300 mg/m\^2, to a maximum of 600 mg) 3 days prior to the tecemotide(LBLP25) administration at week 5 of the weekly treatment phase and 3 days prior to every tecemotide (L-BLP25) administration during the treatment phase with 6-Weekly administration of tecemotide (L-BLP25), commencing at Week-14 up to a maximum treatment period of 2 years.

Tecemotide (L-BLP25) Plus Multiple Low Dose Cyclophosphamide

Tecemotide (L-BLP25): After receiving multiple low dose cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 mcg of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide \[L-BLP25\]) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy was documented.

Multiple low dose cyclophosphamide: An IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of cyclophosphamide was given 3 days before the first vaccine treatment plus an IV dose of cyclophosphamide (300 mg/m\^2, to a maximum of 600 mg) 3 days prior to the tecemotide(LBLP25) administration at week 5 of the weekly treatment phase and 3 days prior to every tecemotide (L-BLP25) administration during the treatment phase with 6-Weekly administration of tecemotide (L-BLP25), commencing at Week-14 up to a maximum treatment period of 2 years.

Safety analysis set included all the randomized participants who received at least 1 dose of trial treatment.

Tecemotide (L-BLP25): After receiving multiple low dose cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 mcg of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide(L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy was documented.

Multiple low dose cyclophosphamide: An IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of cyclophosphamide was given 3 days before the first vaccine treatment plus an IV dose of cyclophosphamide (300 mg/m\^2, to a maximum of 600 mg) 3 days prior to the tecemotide(LBLP25) administration in Weeks 1 and 5 of the weekly treatment phase and 3 days prior to every tecemotide (L-BLP25) administration during the treatment phase with 6-Weekly administration of tecemotide (L-BLP25), commencing at Week-14 up to a maximum treatment period of 2 years.

Immunological diagnostic analysis set was defined as the subset of safety analysis set consisting of all the participants with at least one complete set of baseline (baseline/cyclophosphamide infusion visit or both), Week 5, and Week 9 data of either ELISPOT, proliferation assay or cytokine assay.

Number of Participants With Overall Induced Mucinous Glycoprotein-1 (MUC-1)-Specific Immune Response

Baseline immune response

MUC1 specific immune response at Week 9

Tecemotide (L-BLP25): After receiving multiple low dose cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 mcg of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide(L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy was documented.

Multiple low dose cyclophosphamide: An IV infusion of 300 mg/m\^2 (to a maximum 600 mg/m\^2) of cyclophosphamide was given 3 days before the first vaccine treatment plus an IV dose of cyclophosphamide (300 mg/m\^2, to a maximum of 600 mg) 3 days prior to the tecemotide(LBLP25) administration at week 5 of the weekly treatment phase and 3 days prior to every tecemotide (L-BLP25) administration during the treatment phase with 6-Weekly administration of tecemotide (L-BLP25), commencing at Week-14 up to a maximum treatment period of 2 years.

Number of Participants With Baseline Immune Response and Initial Increase of MUC1 Specific Immune Response

HLA A01 (n=3, 7)

HLA A01 not present (n=14, 8)

HLA A02 present (n=10, 10)

HLA A02 not present (n=7, 5)

HLA A03 present (n=4, 3)

HLA A03 not present (n=13, 12)

HLA A24 present (n=7, 1)

HLA A24 not present (n=10, 14)

HLA A68 present (n=2, 3)

HLA A68 not present (n=15, 12)

HLA B07 present (n=6, 5)

HLA B07 not present (n=11, 10)

HLA B08 present (n=3, 6)

HLA B08 not present (n=14, 9)

HLA B15 present (n=4, 1)

HLA B15 not present (n=13, 14)

HLA B27 present (n=3, 2)

HLA B27 not present (n=14, 13)

HLA B35 present (n=2, 4)

HLA B35 not present (n=15, 11)

HLA B44 present (n=4, 2)

HLA B44 not present (n=13, 13)

HLA C01 present (n=1, 4)

HLA C01 not present (n=16, 11)

HLA C02 present (n=3, 1)

HLA C02 not present (n=14, 14)

HLA C03 present (n=9, 2)

HLA C03 not present (n=8, 13)

HLA C04 present (n=1, 3)

HLA C04 not present (n=16, 12)

HLA C07 present (n=12, 10)

HLA C07 not present (n=5, 5)

HLA DQB02 present (n=2, 6)

HLA DQB02 not present (n=15, 9)

HLA DQB03 present (n=11, 9)

HLA DQB03 not present (n=6, 6)

HLA DQB05 present (n=6, 2)

HLA DQB05 not present (n=11, 13)

HLA DQB06 present (n=7, 5)

HLA DQB06 not present (n=10, 10)

HLA DRB01 present (n=3, 1)

HLA DRB01 not present (n=14, 14)

HLA DRB03 present (n=2, 6)

HLA DRB03 not present (n=15, 9)

HLA DRB04 present (n=11, 6)

HLA DRB04 not present (n=6, 9)

HLA DRB11 present (n=2, 5)

HLA DRB11 not present (n=15, 10)

HLA DRB13 present (n=5, 2)

HLA DRB13 not present (n=12, 13)

HLA DRB15 present (n=5, 3)

HLA DRB15 not present (n=12, 12)

Tecemotide (L-BLP25): After receiving multiple low dose cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 mcg of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide(L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy was documented.

Multiple low dose cyclophosphamide: An IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of cyclophosphamide was given 3 days before the first vaccine treatment plus an IV dose of cyclophosphamide (300 mg/m\^2, to a maximum of 600 mg) 3 days prior to the tecemotide(LBLP25) administration at Week 5 of the weekly treatment phase and 3 days prior to every tecemotide (L-BLP25) administration during the treatment phase with 6-Weekly administration of tecemotide (L-BLP25), commencing at Week-14 up to a maximum treatment period of 2 years.

Immunological diagnostic analysis set was defined as the subset of safety analysis set consisting of all the participants with at least 1 complete set of baseline, Week 5, and Week 9 data of either ELISPOT, proliferation assay or cytokine assay. "n" signifies number of participants evaluable for the particular HLA type, respectively.

Number of Participants With Overall Induced Immune Response by Human Leukocyte-associated Antigen (HLA) Type

CR+PR+MR

Percentage of Participants With Objective Clinical Response (Complete Response [CR], or Partial Response [PR], or Minimal Response [MR]

Time to Progression (TTP)

Time to Anti-tumor Therapy

TEAEs

Serious TEAEs

NCI-CTC Grade 3 and 4 TEAEs

TEAEs leading to discontinuation of treatment

ISRs

Number of Participants With Treatment Emergent Adverse Events (TEAEs),Serious TEAEs, TEAEs of Grade 3 or 4 According to NCI-CTCAE v3.0, TEAEs Leading to Discontinuation and Injection Site Reactions (ISRs)

Tecemotide (L-BLP25): After receiving single low dose cyclophosphamide, participants received 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide (L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy was documented.

Single low dose cyclophosphamide: An intravenous (IV) infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before the first vaccine treatment.

Pharmaceutical Solutions

After receiving cyclophosphamide, participants will receive 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 is documented.

A single intravenous infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide will be given 3 days before first tecemotide (L-BLP25) vaccination.

A single infusion (IV) of 0.9% Saline solution instead of cyclophosphamide but in the same calculated dose will be given three days before first placebo vaccination. Subjects will then receive eight 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 is documented.

The purpose of this study is to determine whether the cancer vaccine tecemotide (L-BLP25) in addition to best supportive care is effective in prolonging the lives of subjects with unresectable stage III non-small cell lung cancer, compared to best supportive care alone.

A local ancillary (sub) study in European centers will evaluate the immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination.

Ancillary Trial: An exploratory investigation of immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination.

The ancillary study is a sub-study within START. This is an exploratory investigation of the immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination. The main objective is to evaluate whether administration of single-shot, low-dose cyclophosphamide followed by tecemotide (L-BLP25) vaccinations induces specific immune response in peripheral blood to BLP25 (the mucinous glycoprotein 1 \[MUC1\] antigen) as well as a modulation of cellular and soluble components of the immune response in subjects with unresectable stage III NSCLC.

Twenty-five of the European START sites will participate in the ancillary study.

Sample size: up to 60 to 80 subjects

All inclusion criteria specified in the START clinical trial protocol except for hemoglobin \>= 100 gram/Liter (g/L)

All exclusion criteria are the same as specified in the START clinical trial protocol

Schedule of events: Blood samples will be taken at baseline, visit week 4, 8 13 and 25 (80 milliliter (mL) whole blood each)

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

A Multi-center Phase III Randomized, Double-blind Placebo-controlled Study of the Cancer Vaccine Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Non-small Cell Lung Cancer (NSCLC) Subjects With Unresectable Stage III Disease.

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.

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.

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.

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.

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.

EMD Serono

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).

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.

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.

Saline + Placebo

ITT population included all the subject who were randomized.

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.

Overall Survival

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) as Measured by the Lung Cancer Symptom Scale (LCSS)

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Tecemotide (L-BLP25) in Participants With Stage III Unresectable Non-small Cell Lung Cancer (NSCLC) Following Primary Chemoradiotherapy	NCT00960115	Non-small Cell ...	Tecemotide (L-B... Single low dose... Placebo Saline	20 Years -	Merck KGaA, Darmstadt, Germany
Study of Tecemotide (L-BLP25) in Subjects With Slowly Progressive Multiple Myeloma With no Symptoms and Who Have Had no Chemotherapy	NCT01094548	Multiple Myelom...	Tecemotide (L-B... Tecemotide (L-B... Single low dose... Multiple low do...	18 Years -	Merck KGaA, Darmstadt, Germany
Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START)	NCT00409188	Non-small Cell ...	Tecemotide (L-B... Single low dose... Placebo	18 Years -	EMD Serono
Cancer Vaccine Study for Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) in the Asian Population	NCT01015443	Non-Small Cell ...	Tecemotide Single low dose... Placebo Saline Best Supportive...	18 Years -	Merck KGaA, Darmstadt, Germany
Phase 2b Randomized Controlled Study of Tecemotide (L-BLP25) for Immunotherapy of NSCLC (Non-Small Cell Lung Cancer)	NCT00157209	Lung Neoplasms Carcinoma, Non-...	Tecemotide (L-B... Single low dose... Best Supportive...	18 Years -	Merck KGaA, Darmstadt, Germany
Cancer Vaccine Study for Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) in the Asian Population	NCT01015443	Non-Small Cell ...	Tecemotide Single low dose... Placebo Saline Best Supportive...	18 Years -	Merck KGaA, Darmstadt, Germany

Spots Global Cancer Trial Database for single low dose cyclophosphamide