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

Phase 1

Completed

Conditions: Non-small Cell Lung Cancer

Interventions: Biological: Tecemotide (L-BLP25)
Biological: Placebo
Other: Saline
Drug: Single low dose cyclophosphamide

Registration Number: NCT00960115

Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 178

Inclusion Criteria

Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of greater than or equal to (>=) 50 Gray (Gy). Participant must have completed the primary thoracic chemoradiotherapy at least 4 weeks and no later than 12 weeks prior to randomization
Written informed consent given before any study-related activities are carried out.
Histologically or cytologically documented unresectable stage III NSCLC. Cancer stage must be confirmed and documented by Computed Tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scan
Documented stable disease or objective response, according to RECIST, after primary chemoradiotherapy for unresectable stage III disease, within four weeks prior to randomization
Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of >= 50 Gy
Eastern cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate bone marrow function
Greater than or equal to 20 years of age

Exclusion Criteria

Lung cancer-specific therapy (including surgery), other than primary chemoradiotherapy. Note: exploratory surgery before study entry is allowed
Immunotherapy (e.g., interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) received within four weeks prior to randomization
Malignant pleural/pericardial effusion or pleural dissemination or separate tumor nodules in the same lobe at initial diagnosis and/or at study entry
Past or current history of neoplasm other than lung carcinoma, except for adequately treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least five years
Autoimmune disease
A recognized immunodeficiency disease including cellular immunodeficiencies, hypogamma-globulinemia, or dysgammaglobulinemia; participants who have hereditary or congenital/acquired immunodeficiencies
Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy, including presence of diffuse radiation pneumonitis spreading out of the involved field
Known Hepatitis B and/or C
Clinically significant hepatic dysfunction
Clinically significant renal dysfunction
Clinically significant cardiac disease
Splenectomy
Infectious process that, in the opinion of the investigator, could compromise the subject's ability to mount an immune response
Pregnant or breast-feeding women. Participants whom the investigator considers may be at risk of pregnancy will have a pregnancy test performed per institutional standard. Male and female subjects who have a reproductive ability, unless using effective contraception as determined by the investigator throughout the study until at least 6 months after the last study treatment
Known drug abuse or alcohol abuse
Legal incapacity or limited legal capacity

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Saline	Saline	Control
Tecemotide (L-BLP25) + Cyclophosphamide	Tecemotide (L-BLP25)	Active
Tecemotide (L-BLP25) + Cyclophosphamide	Single low dose cyclophosphamide	Active
Placebo + Saline	Placebo	Control

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) Time	Time from randomization to death or last day known to be alive reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).	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.

Secondary Outcome Measures

Name	Time	Method
Time To Progression (TTP) - Investigator Read	Time from randomization to PD, reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).	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.
Time to Treatment Failure (TTF)	Time from randomization to discontinuation of trial treatment, reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).	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.
Progression Free Survival (PFS) Time - Investigator Read	Time from randomization to disease progression, death or last tumor assessment, reported between day of first subject randomized in Step 2 (i.e. 03 Feb 2010), until clinical cut-off date (i.e. 01 May 2014).	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.