A Phase 3, Randomized, Double-blind, Placebo-controlled Study For Subjects With Locally-advanced Unresectable or Metastatic Synovial Sarcoma (V943-003, IMDZ-04-1702)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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 Participants Following First Line Systemic Anti-cancer Therapy (V943-003, IMDZ-04-1702)

Conditions
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Synovial Sarcoma, Cancer, Soft Tissue Sarcoma, Sarcoma, Metastatic Sarcoma

Intervention / Treatment
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* Biological: LV305
* Biological: G305
* Other: LV305-matching placebo
* Other: G305-matching placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>A sequential regimen of LV305-matching placebo and G305-matching placebo. | Other: LV305-matching placebo<br>* Administered via SC injection.<br>Other: G305-matching placebo<br>* Administered via IM injection.<br>|
| Experimental: CMB305<br>A sequential regimen of LV305 and G305. | Biological: LV305<br>* Administered via subcutaneous (SC) injection.<br>Biological: G305<br>* Administered via intramuscular (IM) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | From randomization to investigator-determined date of disease progression or death, assessed up to 24 months. | 
| Overall Survival (OS) | OS is defined as the time from randomization to the date of death. | From randomization to date of death, assessed up to 66 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From last dose of CMB305 to initiation of new therapy, assessed up to 24 months. | 
| 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. | From randomization to investigator-determined date of disease progression or death, assessed up to 24 months. | 
| 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. | From randomization to investigator-determined date of disease progression, assessed up to 24 months. | 
| 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. | From randomization to investigator-determined date of disease progression or death, assessed up to approximately 2 months. | 
| 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). | From Day 1 up to 12 months | 
| 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. | Up to approximately 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Synovate Study, NY-ESO-1, cancer vaccine, Sarcoma, soft tissue sarcoma, immunotherapy