Trial Outcomes & Findings for Tecemotide Following Concurrent Chemo-radiotherapy for Non-small Cell Lung Cancer (NCT NCT02049151)

NCT ID: NCT02049151

Last Updated: 2017-08-23

Results Overview

Overall survival (OS) was defined as the time (in months) from randomization to death. Data has been presented in terms of number subjects who died and number of censored subjects.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

35 participants

Primary outcome timeframe

Time from date of randomization until death, assessed maximum up to 16 months

Results posted on

2017-08-23

Participant Flow

First/last subject(informed consent): 21 Mar 2014/11 Sep 2014. Study completion date: 02 Jul 2015.

50 subjects were screened for eligibility; 15 excluded (mainly due to non-fulfillment of inclusion or exclusion criteria) and 35 subjects were randomized. Three subjects were randomized but were not treated.

Participant milestones

Participant milestones
Measure	Tecemotide (L-BLP25) + Cyclophosphamide 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 tecemotide dosing, tecemotide (L-BLP25) (806 micrograms \[mcg\]) was administered weekly subcutaneously for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (806 mcg) were administered every 6 weeks until disease progression was documented.	Placebo + Saline Single dose of saline (sodium chloride, 9 grams per liter \[g/L\]) was administered intravenously, 3 days prior to the tecemotide dosing, placebo doses matched to tecemotide (L-BLP25) was administered weekly subcutaneously 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 disease progression was documented.
Overall Study STARTED	15	17
Overall Study COMPLETED	15	17
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tecemotide Following Concurrent Chemo-radiotherapy for Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=15 Participants Single dose of cyclophosphamide (300 mg/m\^2 to a maximum of 600 mg) was administered intravenously, 3 days prior to the tecemotide dosing, tecemotide (L-BLP25) (806 mcg) was administered weekly subcutaneously for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (806 mcg) were administered every 6 weeks until disease progression was documented.	Placebo + Saline n=17 Participants Single dose of saline (sodium chloride, 9 g/L) was administered intravenously, 3 days prior to the tecemotide dosing, placebo doses matched to tecemotide (L-BLP25) was administered weekly subcutaneously 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 disease progression was documented.	Total Title n=32 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=93 Participants	10 Participants n=4 Participants	15 Participants n=27 Participants
Age, Categorical >=65 years	10 Participants n=93 Participants	7 Participants n=4 Participants	17 Participants n=27 Participants
Age, Continuous Age Continuous	66.2 years STANDARD_DEVIATION 5.99 • n=93 Participants	63.9 years STANDARD_DEVIATION 10.45 • n=4 Participants	65.0 years STANDARD_DEVIATION 8.60 • n=27 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	7 Participants n=4 Participants	9 Participants n=27 Participants
Sex: Female, Male Male	13 Participants n=93 Participants	10 Participants n=4 Participants	23 Participants n=27 Participants

PRIMARY outcome

Timeframe: Time from date of randomization until death, assessed maximum up to 16 months

Population: Safety Analysis Set included all subjects who had taken at least one dose of trial treatment (tecemotide \[L-BLP25\] or placebo), including cyclophosphamide or saline. Analysis was not performed due to the premature termination of this study and the tecemotide program based on negative results in EMR 63325-009 (NCT00960115).

Overall survival (OS) was defined as the time (in months) from randomization to death. Data has been presented in terms of number subjects who died and number of censored subjects.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=15 Participants Single dose of cyclophosphamide (300 mg/m\^2 to a maximum of 600 mg) was administered intravenously, 3 days prior to the tecemotide dosing, tecemotide (L-BLP25) (806 mcg) was administered weekly subcutaneously for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (806 mcg) were administered every 6 weeks until disease progression was documented.	Placebo + Saline n=17 Participants Single dose of saline (sodium chloride, 9 g/L) was administered intravenously, 3 days prior to the tecemotide dosing, placebo doses matched to tecemotide (L-BLP25) was administered weekly subcutaneously 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 disease progression was documented.
Overall Survival Number of deaths	1 subjects	2 subjects
Overall Survival Number for censored	14 subjects	15 subjects

SECONDARY outcome

Timeframe: Time from date of randomization until progressive disease (PD), assessed up to 16 months

Population: Analysis was not performed due to the premature termination of this study and the tecemotide program based on negative results in EMR 63325-009 (NCT00960115).

TTSP was measured from date of randomization to date of disease progression (defined based on RECIST v1.1), using the lung cancer symptom scale (LCSS), a validated questionnaire consisting of an observer scale and a subject scale used to specifically measure symptom changes relevant to quality of life (QoL) for individuals undergoing treatment for lung cancer. Subject scale was used as a tool to determine TTSP. It was a 9-item questionnaire used to document subject-reported outcomes for a variety of lung cancer associated symptoms. The average symptomatic burden index (ASBI) was used to determine differences in the treatment groups. ASBI was the mean of the 6 symptom scores derived from the LCSS questionnaire. Symptom progression was defined as an increase (worsening) of the ASBI score of 10% of the scale breadth (10 mm on a scale of 0-100 mm) from the baseline score on at least 2 consecutive assessments during the period when assessments are performed every 3 weeks and every 6 weeks.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from date of randomization until PD or death, assessed up to 16 months

Population: Analysis was not performed due to the premature termination of this study and the tecemotide program based on negative results in EMR 63325-009 (NCT00960115).

PFS was defined as the time from date of randomization until date of the first documentation of PD or death due to any cause in the absence of documented PD, whichever occurred first. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Subjects without event were censored on the date of last tumor assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from date of randomization until PD, assessed up to 16 months

Population: Analysis was not performed due to the premature termination of this study and the tecemotide program based on negative results in EMR 63325-009 (NCT00960115).

TTP was measured from the date of randomization to the date of tumor progression. Date of tumor progression was date of radiological diagnosis of PD, performed as per RECIST 1.1. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression. For participants alive without tumor progression at time of analysis, the time between date of randomization and date of last trial treatment was calculated and used as a censored observation in the analysis. Subjects dying from causes other than PD was censored at time of death.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from first dose up to 42 days after the last dose of the trial treatment: assessed maximum up to 16 months

Population: Safety Analysis Set included all subjects who had taken at least one dose of trial treatment (tecemotide \[L-BLP25\] or placebo), including cyclophosphamide or saline.

An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. 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. TEAEs occurred between the first dose of study drug and up to 42 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Number of Subjects With TEAEs, Serious TEAEs, NCI-CTC Grade 3/4 TEAEs, TEAEs Leading to Permanent Discontinuation, TEAEs Leading to Death, and ISRs were reported.

Outcome measures

Outcome measures
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=15 Participants Single dose of cyclophosphamide (300 mg/m\^2 to a maximum of 600 mg) was administered intravenously, 3 days prior to the tecemotide dosing, tecemotide (L-BLP25) (806 mcg) was administered weekly subcutaneously for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (806 mcg) were administered every 6 weeks until disease progression was documented.	Placebo + Saline n=17 Participants Single dose of saline (sodium chloride, 9 g/L) was administered intravenously, 3 days prior to the tecemotide dosing, placebo doses matched to tecemotide (L-BLP25) was administered weekly subcutaneously 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 disease progression was documented.
Number Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, National Cancer Institute-Common Toxicity Criteria (NCI-CTC)Grade 3/4 TEAEs, TEAEs Leading to Permanent Discontinuation, TEAEs Leading to Death, Injection Site Reactions (ISRs) Grade 3 or 4 TEAEs	5 subjects	2 subjects
Number Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, National Cancer Institute-Common Toxicity Criteria (NCI-CTC)Grade 3/4 TEAEs, TEAEs Leading to Permanent Discontinuation, TEAEs Leading to Death, Injection Site Reactions (ISRs) TEAEs Leading to Permanent Discontinuation	2 subjects	1 subjects
Number Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, National Cancer Institute-Common Toxicity Criteria (NCI-CTC)Grade 3/4 TEAEs, TEAEs Leading to Permanent Discontinuation, TEAEs Leading to Death, Injection Site Reactions (ISRs) TEAEs	14 subjects	13 subjects
Number Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, National Cancer Institute-Common Toxicity Criteria (NCI-CTC)Grade 3/4 TEAEs, TEAEs Leading to Permanent Discontinuation, TEAEs Leading to Death, Injection Site Reactions (ISRs) Serious TEAEs	4 subjects	1 subjects
Number Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, National Cancer Institute-Common Toxicity Criteria (NCI-CTC)Grade 3/4 TEAEs, TEAEs Leading to Permanent Discontinuation, TEAEs Leading to Death, Injection Site Reactions (ISRs) TEAEs leading to death	0 subjects	0 subjects
Number Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, National Cancer Institute-Common Toxicity Criteria (NCI-CTC)Grade 3/4 TEAEs, TEAEs Leading to Permanent Discontinuation, TEAEs Leading to Death, Injection Site Reactions (ISRs) ISRs	0 subjects	3 subjects

Adverse Events

Tecemotide (L-BLP25) + Cyclophosphamide

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo + Saline

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tecemotide (L-BLP25) + Cyclophosphamide n=15 participants at risk 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 tecemotide dosing, tecemotide (L-BLP25) (806 micrograms \[mcg\]) was administered weekly subcutaneously for 8 weeks, followed by a maintenance treatment phase starting at Week 14, in which subcutaneous vaccinations with tecemotide (L-BLP25) (806 mcg) were administered every 6 weeks until disease progression was documented	Placebo + Saline n=17 participants at risk Single dose of saline (sodium chloride, 9 grams per liter \[g/L\]) was administered intravenously, 3 days prior to the tecemotide dosing, placebo doses matched to tecemotide (L-BLP25) was administered weekly subcutaneously 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 disease progression was documented.
Cardiac disorders Atrial fibrillation	6.7% 1/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	0.00% 0/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.
Endocrine disorders Autoimmune thyroiditis	6.7% 1/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	0.00% 0/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.
Infections and infestations Pneumonia	20.0% 3/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	5.9% 1/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.
Infections and infestations Pseudomonal sepsis	6.7% 1/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	0.00% 0/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	5.9% 1/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	5.9% 1/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.7% 1/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	0.00% 0/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	6.7% 1/15 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.	0.00% 0/17 • Time from first dosing day until 42 days following the last vaccination of tecemotide (L-BLP25) or placebo assessed maximum up to 16 months.

Other adverse events

Additional Information

Merck KGaA Communication Centre

Merck Serono, a division of Merck KGaA

Phone: 496151725200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first publication will be publication of results of the analysis of primary endpoint(s) that will include data from all trial centers. Any publications and presentations of results, either in whole or in part, by investigators or their representatives will require pre-submission review by the sponsor/CRO. Sponsor will not suppress or veto publications, but maintains right to delay publication in order to protect intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER