Cancer, Metastatic Sarcoma, Sarcoma, Soft Tissue Sarcoma, Synovial Sarcoma
Conditions
Keywords
Synovate Study, NY-ESO-1, cancer vaccine, Sarcoma, soft tissue sarcoma, immunotherapy
Brief summary
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.
Detailed description
The Synovate Study is a global, randomized, double-blind, placebo-controlled, phase 3 study in patients with unresectable, locally-advanced or metastatic New York esophageal squamous cell carcinoma 1 (NY-ESO-1) positive synovial sarcoma following first-line systemic anti-cancer therapy.
Interventions
BIOLOGICALLV305
Administered via subcutaneous (SC) injection.
BIOLOGICALG305
Administered via intramuscular (IM) injection.
OTHERLV305-matching placebo
Administered via SC injection.
OTHERG305-matching placebo
Administered via IM injection.
Sponsors
Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Selected Inclusion Criteria: * Histological diagnosis of synovial sarcoma * Immunohistochemistry (IHC) results from tumor biopsy for New York esophageal squamous cell carcinoma 1 (NY-ESO-1) are positive * Participants have received at least 4 but no more than 8 cycles of first-line anthracycline or ifosfamide-containing systemic anti-cancer therapy regimen * Must have documentation of no evidence of disease progression of the tumor during or after completion of first line systemic anti-cancer therapy * ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1 * Age \>/= 12 years * Life expectancy of at least 6 months Selected
Exclusion criteria
* Have received last dose of first-line systemic anti-cancer therapy or date of most recent local regional therapy \>28 days prior to day 1 * Have received prior anti-NY-ESO-1 therapy * Have received first-line systemic anti-cancer therapy with an agent other than anthracycline or ifosfamide * Have received treatment with systemic immunomodulatory agents within 28 days prior to administration of the first dose of CMB305, or 5 half-lives of the drug, whichever occurs sooner. * Have significant immunosuppression from concurrent, recent, or anticipated need for chronic treatment with systemic immunosuppressive dose of corticosteroids or immunosuppressive medications. * Have psychiatric or other medical illness, or any other condition that in the opinion of the investigator prevents compliance with the study procedures or ability to provide valid informed consent. * Have history of uncontrolled autoimmune disease. * Have a significant electrocardiogram finding or cardiovascular disease * have inadequate organ function per protocol * History of other cancer within 3 years * Evidence of active tuberculosis or recent clinically-significant infection requiring systemic therapy. * Evidence of active Hepatitis B, Hepatitis C, or Human Immunodeficiency virus (HIV) infection * Have a history of brain metastasis * Have received cancer therapies including chemotherapy, radiation, biologic, or kinase inhibitors, granulocyte-colony stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 3 weeks prior ot the first scheduled dose of CMB305 * Female of child bearing potential who is pregnant, is planning to become pregnant, or is breast feeding; or male who is sexually active with a female of child bearing potential who is planning to become pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From randomization to investigator-determined date of disease progression or death, assessed up to 24 months. | 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). |
| Overall Survival (OS) | From randomization to date of death, assessed up to 66 months. | OS is defined as the time from randomization to the date of death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From randomization to investigator-determined date of disease progression, assessed up to 24 months. | 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. |
| Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | From randomization to investigator-determined date of disease progression or death, assessed up to approximately 2 months. | 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. |
| Time to Next Treatment (TTNT) | From last dose of CMB305 to initiation of new therapy, assessed up to 24 months. | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 2 months | The number of all participants who discontinued study treatment due to an AE is presented. |
| Quality of Life (QoL): EuroQol 5-Dimension 5 Level (EQ-5D-5L) and EuroQol 5-Dimension Youth (EQ-5D-Y) Questionnaires | From Day 1 up to 12 months | QoL evaluated using the EQ-5D-5L for participants ≥18 years of age or using the EQ-5D-Y for 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 thus 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). |
| Distant Metastasis Free Survival (DMFS) | From randomization to investigator-determined date of disease progression or death, assessed up to 24 months. | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo CMB305 placebo control | 0 |
| CMB305 CMB305: Sequentially administered LV305 \[lentiviral vector encoding New York esophogeal squamous cell carcinoma-1 {NY-ESO-1} gene\] and G305 \[NY-ESO-1 recombinant protein plus glucopyranosyl lipid A stable emulsion {GLA-SE}\] | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated by Sponsor | 0 | 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Survival (OS)
OS is defined as the time from randomization to the date of death.
Time frame: From randomization to date of death, assessed up to 66 months.
Population: No data were collected or analyzed for this outcome measure due to early termination of the study.
Primary
Progression-Free Survival (PFS)
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).
Time frame: From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
Population: No data were collected or analyzed for this outcome measure due to early termination of the study.
Secondary
Distant Metastasis Free Survival (DMFS)
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.
Time frame: From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.
Population: No data were collected or analyzed for this outcome measure due to early termination of the study.
Secondary
Number of Participants Who Discontinued Study Treatment Due to an AE
The number of all participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 2 months
Population: All participants taking any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CMB305 | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
Secondary
Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)
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.
Time frame: From randomization to investigator-determined date of disease progression or death, assessed up to approximately 2 months.
Population: All participants taking any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CMB305 | Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) | 1 Participants |
Secondary
Overall Response Rate (ORR)
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.
Time frame: From randomization to investigator-determined date of disease progression, assessed up to 24 months.
Population: No data were collected or analyzed for this outcome measure due to early termination of the study.
Secondary
Quality of Life (QoL): EuroQol 5-Dimension 5 Level (EQ-5D-5L) and EuroQol 5-Dimension Youth (EQ-5D-Y) Questionnaires
QoL evaluated using the EQ-5D-5L for participants ≥18 years of age or using the EQ-5D-Y for 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 thus 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).
Time frame: From Day 1 up to 12 months
Population: No data were collected or analyzed for this outcome measure due to early termination of the study.
Secondary
Time to Next Treatment (TTNT)
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.
Time frame: From last dose of CMB305 to initiation of new therapy, assessed up to 24 months.
Population: No data were collected or analyzed for this outcome measure due to early termination of the study.