Clinical Trial Results:
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy and Safety of CMB305 in Unresectable Locally-advanced or Metastatic NY-ESO-1+ Synovial Sarcoma Subjects Following First-line Systemic Anti-cancer Therapy
Summary
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EudraCT number |
2018-000824-32 |
Trial protocol |
GB DK |
Global end of trial date |
20 Nov 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jul 2020
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First version publication date |
03 Jul 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
V943A-003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03520959 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IMDZ-04-1702: Immune Design Corp. Protocol Number | ||
Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Nov 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Nov 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess if the CMB305 vaccine regimen may help the body's immune system to slow or stop the growth of synovial sarcoma tumor and improve survival.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Sep 2018
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
1
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was terminated early by the Sponsor. | ||||||||||
Pre-assignment
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Screening details |
Participants with synovial sarcoma expressing New York esophageal squamous cell carcinoma-1 (NY-ESO-1) were recruited in the United States. | ||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||
Roles blinded |
Investigator, Carer, Assessor, Subject | ||||||||||
Arms
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Arm title
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CMB305 | ||||||||||
Arm description |
A sequential regimen of LV305 and G305. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
LV305
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administered via subcutaneous (SC) injection.
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Investigational medicinal product name |
G305
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Administered via intramuscular (IM) injection.
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Baseline characteristics reporting groups
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Reporting group title |
CMB305
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Reporting group description |
A sequential regimen of LV305 and G305. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
CMB305
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Reporting group description |
A sequential regimen of LV305 and G305. |
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End point title |
Progression-Free Survival (PFS) [1] | ||||||||
End point description |
PFS is defined as the time from randomization to the investigator-determined date of disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Primary
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End point timeframe |
From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The study terminated prior to data collection and analysis. |
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Notes [2] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Overall Survival (OS) [3] | ||||||||
End point description |
OS is defined as the time from randomization to the date of death. No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Primary
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End point timeframe |
From randomization to date of death, assessed up to 66 months.
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The study terminated prior to data collection and analysis. |
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Notes [4] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Time to Next Treatment (TTNT) | ||||||||
End point description |
TTNT is defined as the time from randomization to the start of post-study treatment subsequent intervention: [TTNT = start date of subsequent intervention – randomization date + 1]. Subsequent intervention includes anticancer therapy, cancer-related surgery and local regional therapy. Participants who do not start any post-study treatment intervention will be censored at their last known date of being alive. No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Secondary
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End point timeframe |
From last dose of CMB305 to initiation of new therapy, assessed up to 24 months.
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Notes [5] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Distant Metastasis Free Survival (DMFS) | ||||||||
End point description |
DMFS is defined as the time from randomization to evidence of a new distant metastasis not documented at time of randomization: [DMFS = a new distant metastasis documented date – randomization date + 1]. Participants who do not have any new distant metastasis will be censored at their last tumor assessment. No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Secondary
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End point timeframe |
From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
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Notes [6] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Overall Response Rate (ORR) | ||||||||
End point description |
ORR defined by RECIST v1.1 will be summarized by the number and percent of subjects who achieve a complete response (CR) or partial response (PR) based on the investigator’s assessment. ORR will be compared between treatment arms using a logistic regression. No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Secondary
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End point timeframe |
From randomization to investigator-determined date of disease progression, assessed up to 24 months.
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Notes [7] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | ||||||
End point description |
Safety will be assessed primarily based on reported adverse events (AEs), medical events of interest (MEOIs), laboratory values, and concomitant medications reported from initiation of treatment with CMB305 or placebo. No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Secondary
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End point timeframe |
From randomization to investigator-determined date of disease progression or death, assessed up to approximately 2 months.
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Notes [8] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Quality of Life (QoL): EuroQol 5-Dimension 5 Level (EQ-5D-5L) and EuroQol 5-Dimension Youth (EQ-5D-Y) Questionnaires | ||||||
End point description |
QoL evaluated using the EQ-5D-5L (participants ≥18 years of age) or the EQ-5D-Y (participants 12 to <18 years of age). EQ-5D-5L descriptive system is comprised of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Participants indicated their health state by choosing the appropriate level from each dimension. The 5 digit health states obtained for each dimension were then converted into a single median index value using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. In the EQ-VAS, participants recorded their health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Secondary
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End point timeframe |
From Day 1 up to 12 months
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Notes [9] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Number of Participants Who Discontinued Study Treatment Due to an AE | ||||||
End point description |
The number of all participants who discontinued study treatment due to an AE is presented. No data were collected or analyzed for this outcome measure due to early termination of the study.
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End point type |
Secondary
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End point timeframe |
Up to approximately 2 months
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Notes [10] - The study terminated early and no endpoint data were analyzed. |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Up to approximately 2 months
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Adverse event reporting additional description |
0 participants are reported due to the risk of identification of a person.
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Assessment type |
Systematic | ||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
n/a
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Reporting groups
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Reporting group title |
CMB305
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Reporting group description |
Sequentially administered LV305 and G305. | ||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: The study terminated prior to data collection and analysis. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Study was stopped early due to Sponsor decision. |