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

• Sponsor: Immune Design (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03520959
• Collaborator: (none)
• Enrollment: 1
• Locations: 29
• Arms: 2
• Actual Duration (Months): 2.1
• Patients Per Site: 0
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Synovial Sarcoma; Cancer; Soft Tissue Sarcoma; Sarcoma; Metastatic Sarcoma	Biological: LV305; Biological: G305; Other: LV305-matching placebo; Other: G305-matching placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Sep 18, 2018
• Actual Primary Completion Date: Nov 20, 2018
• Actual Study Completion Date: Nov 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo A sequential regimen of LV305-matching placebo and G305-matching placebo.	Other: LV305-matching placebo; Administered via SC injection.; Other: G305-matching placebo; Administered via IM injection.
Experimental: CMB305 A sequential regimen of LV305 and G305.	Biological: LV305; Administered via subcutaneous (SC) injection.; Biological: G305; Administered via intramuscular (IM) injection.

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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).

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic- Scottsdale	Scottsdale	Arizona	United States	85259
2	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
3	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	Stanford University	Palo Alto	California	United States	94305
5	Sarcoma Oncology Center	Santa Monica	California	United States	90403
6	University of Colorado Cancer Center	Boulder	Colorado	United States	80309
7	Yale University School of Medicine- Cancer Center	New Haven	Connecticut	United States	06520
8	University of Miami	Coral Gables	Florida	United States	33146
9	Mayo Clinic- Jacksonville	Jacksonville	Florida	United States	32224
10	Moffitt Cancer Center at USF	Tampa	Florida	United States	33612
11	Northwestern	Chicago	Illinois	United States	60611
12	Dana Farber Cancer Institute/Mass General Hospital	Boston	Massachusetts	United States	02215
13	University of Michigan	Ann Arbor	Michigan	United States	48109
14	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
15	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
16	Hackensack University Medical Center	Edison	New Jersey	United States	08837
17	Cohen Children's Medical Center (Northwell)	Astoria	New York	United States	11105
18	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
19	Duke University	Durham	North Carolina	United States	27708
20	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
21	Ohio State University	Columbus	Ohio	United States	43210
22	Oregon Health and Science University	Portland	Oregon	United States	97239
23	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
24	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15224
25	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
26	MD Anderson Cancer Center	Houston	Texas	United States	77030
27	Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
28	University of Alberta Hospital- Cross Cancer Institute	Edmonton		Canada
29	McGill University	Montréal-Est		Canada

Sponsors and Collaborators

• Immune Design

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 19, 2018
• Statistical Analysis Plan - May 25, 2018

More Information

Publications

None provided.

• Responsible Party: Immune Design
• ClinicalTrials.gov Identifier: NCT03520959
• Other Study ID Numbers: IMDZ-04-1702; V943A-003
• First Posted: May 11, 2018
• Last Update Posted: Apr 16, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Immune Design: Synovate Study; NY-ESO-1; cancer vaccine; Sarcoma; soft tissue sarcoma; immunotherapy
• Additional relevant MeSH terms: Sarcoma; Sarcoma, Synovial

Study Results

Participant Flow

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Period Title: Overall Study
STARTED	0	1
COMPLETED	0	0
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Placebo	CMB305	Total
Arm/Group Description	CMB305 placebo control	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}]	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Sex: Female, Male () []
Female
Male
Ethnicity (NIH/OMB) () []
Hispanic or Latino
Not Hispanic or Latino
Unknown or Not Reported
Race (NIH/OMB) () []
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
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).
Time Frame	From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed for this outcome measure due to early termination of the study.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	0

2. Primary Outcome

Title	Overall Survival (OS)
Description	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.

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed for this outcome measure due to early termination of the study.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	0

3. Secondary Outcome

Title	Time to Next Treatment (TTNT)
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.
Time Frame	From last dose of CMB305 to initiation of new therapy, assessed up to 24 months.

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed for this outcome measure due to early termination of the study.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	0

4. Secondary Outcome

Title	Distant Metastasis Free Survival (DMFS)
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.
Time Frame	From randomization to investigator-determined date of disease progression or death, assessed up to 24 months.

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed for this outcome measure due to early termination of the study.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	0

5. Secondary Outcome

Title	Overall Response Rate (ORR)
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.
Time Frame	From randomization to investigator-determined date of disease progression, assessed up to 24 months.

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed for this outcome measure due to early termination of the study.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	0

6. Secondary Outcome

Title	Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE)
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.
Time Frame	From randomization to investigator-determined date of disease progression or death, assessed up to approximately 2 months.

Outcome Measure Data

Analysis Population Description

All participants taking any amount of study drug.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	1
Number [Participants]	1 Infinity

7. Secondary Outcome

Title	Quality of Life (QoL): EuroQol 5-Dimension 5 Level (EQ-5D-5L) and EuroQol 5-Dimension Youth (EQ-5D-Y) Questionnaires
Description	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

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed for this outcome measure due to early termination of the study.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	0

8. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an AE
Description	The number of all participants who discontinued study treatment due to an AE is presented.
Time Frame	Up to approximately 2 months

Outcome Measure Data

Analysis Population Description

All participants taking any amount of study drug.

Arm/Group Title	Placebo	CMB305
Arm/Group Description	CMB305 placebo control	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}]
Measure Participants	0	1
Number [Participants]	0 NaN

Adverse Events

Time Frame	Up to approximately 2 months
Adverse Event Reporting Description	0 participants are reported due to the risk of identification of a person.
Arm/Group Title	Placebo		CMB305
Arm/Group Description	CMB305 placebo control		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}]
All Cause Mortality
	Placebo		CMB305
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Placebo		CMB305
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Placebo		CMB305
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Study was stopped early due to Sponsor decision.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.