Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)

• Sponsor: Immune Design (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02609984
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 89
• Locations: 18
• Arms: 2
• Actual Duration (Months): 45.3
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label Phase 2 randomized study that will examine the use of the study agents, CMB305 (sequentially administered LV305 which is a dendritic cell-targeting viral vector expressing the New York Esophageal Squamous Cell Carcinoma 1 gene [NY-ESO-1] and G305 which is a NY-ESO-1 recombinant protein plus glucopyranosyl lipid adjuvant-stable emulsion [GLA-SE]) in combination with atezolizumab or atezolizumab alone, in participants with locally advanced, relapsed or metastatic sarcoma (synovial or myxoid/round cell liposarcoma) expressing the NY-ESO-1 protein.

There is no formal primary hypothesis for this study.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma; Myxoid/Round Cell Liposarcoma; Synovial Sarcoma; Metastatic Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Locally Advanced Sarcoma; Liposarcoma	Biological: CMB305; Biological: atezolizumab	Phase 2

Detailed Description

This study is designed to investigate and examine the time to progression and overall survival for CMB305 in combination with atezolizumab or atezolizumab alone in the treatment of participants with sarcoma expressing NY-ESO-1 protein.

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Phase 2 Trial of CMB305 (Sequentially Administered LV305 and G305) and Atezolizumab in Patients With Locally Advanced, Relapsed, or Metastatic Sarcoma Expressing NY-ESO-1
• Actual Study Start Date: Apr 29, 2015
• Actual Primary Completion Date: Feb 6, 2019
• Actual Study Completion Date: Feb 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CMB305 (sequentially administered LV305 and G305)+Atezolizumab Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered intradermally (ID) on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered intramuscularly (IM) and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Biological: CMB305; A combination of LV305 administered intradermally (ID) and G305 administered intramuscularly (IM); Biological: atezolizumab; IV Infusion; Other Names: TECENTRIQ®
Active Comparator: Atezolizumab Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.	Biological: atezolizumab; IV Infusion; Other Names: TECENTRIQ®

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 36.1 months]

   PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use immune-related response criteria (irRC) confirmation and unidimensional tumor measurements as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.

2. Overall Survival (OS) [Up to approximately 36.1 months]

   OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data.

Secondary Outcome Measures

1. Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) [Up to approximately 42 days]

   DLTs will be evaluated during the safety run-in period. Any treatment emergent Grade 3 or higher adverse event (AE) that occurs in the first 42 days after initiation of study treatment, that is deemed possibly, probably or definitely related to the combination of CMB305 and atezolizumab will be considered a DLT with the following exceptions: Alopecia or vomiting (unless not controlled by optimal anti-emetics) Hepatic enzyme elevations associated with the baseline Grade 2 abnormalities Grade 3 laboratory AEs that are asymptomatic and return to baseline or to Grade 1 within 3 days, unless identified specifically as DLT by the investigator or the Data Monitoring Committee (DMC) Grade 3 fatigue Grade 3 systemic reactions (such as fever, headache, influenza like symptoms, myalgia, malaise, or nausea) that return to baseline or Grade 1 within 3 days of study inoculation

2. Number of Participants Who Experienced At Least One Adverse Event (AE) [Up to approximately 36.1 months]

   An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.

3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Up to approximately 24 months]

   An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

4. Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Month 3]

   PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Participants were evaluated every 6 weeks with radiographic imaging to assess their response to treatment. The PFS rate was calculated as the percentage of participants with PFS at Month 3.

5. Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Month 6]

   PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Participants were evaluated every 6 weeks with radiographic imaging to assess their response to treatment. The PFS rate was calculated as the percentage of participants with PFS at Month 6.

6. Time to Next Treatment (TTNT) [Up to approximately 36.1 months]

   TTNT was the time from date of randomization to the start date of subsequent treatment. Participants were treated for up to approximately 2 years and then followed until next treatment or death. Participants who did not receive subsequent treatment were censored at the date of last contact or death. The TTNT was analyzed using the product-limit (Kaplan-Meier) method for censored data.

7. Distant Metastasis Free Survival (DMFS) [Up to approximately 36.1 months]

   DMFS was the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. Participants without metastasis and death were censored at the date of last contact or death. The DMFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.

8. Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody at Baseline [Baseline (Day 1)]

   The number of participants with anti-NY-ESO-1 antibodies at baseline was measured using an enzyme-linked immunosorbent assay (ELISA) with recombinant NY-ESO1 protein. A titer of >1:100 was considered positive. The number of participants that were anti-NY-ESO-1 antibody positive at baseline is presented.

9. Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody After Induction With Treatment [Up to approximately 24 months]

   The number of participants with anti-NY-ESO-1 antibodies induced after treatment was measured using an enzyme-linked immunosorbent assay (ELISA) with recombinant NY-ESO1protein. A titer of >1:100 was considered positive. The induction of anti-NY-ESO-1 antibody response was defined as a ≥4-fold increase in the titer or the presence of a newly positive response after the first dose of treatment. The number of participants that were anti-NY-ESO-1 antibody positive after induction with treatment is presented.

10. Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells at Baseline [Baseline (Day 1)]

    Anti-NY-ESO-1 CD4 and CD8 positive T-cell responses were measured by interferon gamma detecting enzyme-linked ImmunoSpot (ELISPOT) using isolated CD4 and CD8 positive T cells from peripheral blood mononuclear cells (PBMCs) expanded in vitro with a NY-ESO-1 peptide pool (20-mer peptides, 10-mer overlap) and considered positive if there were >50 spot-forming units/50,000 cells observed for NY-ESO-1 peptides and a ≥2-fold increase in spot-forming units compared with a negative control. The number of participants that were anti-NY-ESO-1 T cell positive at baseline is presented.

11. Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells After Induction With Treatment [Up to approximately 24 months]

    Anti-NY-ESO-1 CD4 and CD8 positive T-cell responses were measured by interferon gamma detecting enzyme-linked ImmunoSpot (ELISPOT) using isolated CD4 and CD8 positive T cells expanded with a NY-ESO-1 peptide (20-mer peptides, 10-mer overlap) and considered positive if there were >50 spot-forming units (SPU)/50,000 cells observed for NY-ESO-1 peptides and a ≥2-fold increase in SPU compared with a negative control. The induction of an anti-NYESO-1 CD4 or CD8 positive T-cell response was defined as de novo positive or ≥2-fold rise in the number of SPU after the first dose. A fluorescence-activated cell sorting (FACS)-based intracellular cytokine staining assay for interferon gamma or tumor necrosis factor alpha after stimulation with NY-ESO-1 peptide was also used and staining ≥2-fold above the baseline value was considered positive for T-cell responses. The number of participants that were anti-NY-ESO-1 T cell positive after induction with treatment is presented.

Other Outcome Measures

1. Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 36.1 months]

   ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all lesions in 2 consecutive observations ≥4 weeks apart) or a Partial Response (PR: ≥30% decrease in tumor burden compared with baseline in 2 observations ≥4 weeks apart) per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR is presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Locally advanced, relapsed, or metastatic sarcoma with measurable tumor burden following therapy, as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); the total of all lesions must be ≤12 cm (for synovial sarcoma) or ≤15 cm (for myxoid/round cell liposarcoma [MRCL])

• Tumor histology consistent with synovial sarcoma or MRCL

• Tumor specimen positive for NY-ESO-1 expression by immunohistochemistry (IHC)

• Inadequate response, relapse, and/or unacceptable toxicity with ≥1 prior systemic, surgical, or radiation cancer therapies

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Investigational therapy within 4 weeks prior to CMB305 dosing

• Prior administration of other NY-ESO-1-targeting immunotherapeutics

• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-programmed cell death receptor 1 (PD-1), and anti-programmed cell death ligand (PD-L1) therapeutic antibodies, or any other antibody or drug targeting T-cell costimulation

• Treatment with systemic immunostimulatory agents (including but not limited to interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first dose

• Significant immunosuppression

• Other cancer therapies, including chemotherapy, radiation, biologics or kinase inhibitors within 3 weeks prior to the first scheduled dosing

• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis

• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

• History of other cancer within 3 years

• Evidence of active tuberculosis or recent (<1 week prior to first scheduled dosing) clinically significant infection requiring systemic therapy

• Evidence of active hepatitis B (HepB), hepatitis C (HepC), or Human Immunodeficiency Virus (HIV) infection

• Known active or untreated central nervous system (CNS) metastases

• Pregnant, planning to become pregnant within 6 months of treatment, or nursing

• Known allergy(ies) to any component of CMB305, atezolizumab, or severe allergic reactions to monoclonal antibodies, fusion proteins, or Chinese hamster ovary (CHO) cell products

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Palo Alto	California	United States	94304
2	Sarcoma Oncology Research Center	Santa Monica	California	United States	90403
3	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
4	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
5	Mayo Clinic of Jacksonville	Jacksonville	Florida	United States	32224
6	Georgia Cancer Specialists	Sandy Springs	Georgia	United States	30342
7	Northwestern University Feinburg School of Medicine	Chicago	Illinois	United States	60611
8	University of Iowa Hospital and Clinics	Iowa City	Iowa	United States	52242
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Mayo Clinic Rochester	Rochester	Minnesota	United States	10029
11	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
12	Monter Cancer Research	Lake Success	New York	United States	11042
13	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
14	Duke Cancer Institute	Durham	North Carolina	United States	27710
15	Fox Chase cancer Center	Philadelphia	Pennsylvania	United States	19111
16	Vanderbilt University	Nashville	Tennessee	United States	37232
17	University of Vermont Cancer Center	Burlington	Vermont	United States	05405
18	Scca/Fhcrc	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Immune Design
• Genentech, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 14, 2019
• Study Protocol - Mar 8, 2017

More Information

Publications

None provided.

• Responsible Party: Immune Design
• ClinicalTrials.gov Identifier: NCT02609984
• Other Study ID Numbers: IMDZ-C232; V943A-002; IMDZ-C232
• First Posted: Nov 20, 2015
• Last Update Posted: Jul 7, 2020
• Last Verified: Jun 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Immune Design: immunotherapy; CMB305; LV305; GLA-SE; atezolizumab; NY-ESO-1
• Additional relevant MeSH terms: Sarcoma; Liposarcoma; Sarcoma, Synovial; Liposarcoma, Myxoid; Atezolizumab

Study Results

Participant Flow

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered intradermally (ID) on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered intramuscularly (IM) and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of New York Esophageal Squamous Cell Carcinoma 1 (NY ESO-1) protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Period Title: Overall Study
STARTED	45	44
Treated	45	43
COMPLETED	1	5
NOT COMPLETED	44	39

Baseline Characteristics

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab	Total
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.	Total of all reporting groups
Overall Participants	45	44	89
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.2 (16.52)	46.7 (14.06)	46.4 (15.27)
Sex: Female, Male (Count of Participants)
Female	19 42.2%	19 43.2%	38 42.7%
Male	26 57.8%	25 56.8%	51 57.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 15.6%	6 13.6%	13 14.6%
Not Hispanic or Latino	37 82.2%	34 77.3%	71 79.8%
Unknown or Not Reported	1 2.2%	4 9.1%	5 5.6%
Race/Ethnicity, Customized (Count of Participants)
White	35 77.8%	38 86.4%	73 82%
Asian	3 6.7%	1 2.3%	4 4.5%
Black or African American	1 2.2%	3 6.8%	4 4.5%
American Indian or Alaska Native	2 4.4%	0 0%	2 2.2%
Native Hawaiian or Other	2 4.4%	0 0%	2 2.2%
Other	2 4.4%	0 0%	2 2.2%
Not Reported	0 0%	2 4.5%	2 2.2%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use immune-related response criteria (irRC) confirmation and unidimensional tumor measurements as assessed by Blinded Independent Central Review (BICR). PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame	Up to approximately 36.1 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the electronic Case Report Form (eCRF). Participants were included in the treatment group to which they were randomized.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	44
Median (95% Confidence Interval) [Months]	2.6	1.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4900
	Comments	P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8568
	Confidence Interval	(2-Sided) 95%; 0.5507 to 1.3330
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.

2. Primary Outcome

Title	Overall Survival (OS)
Description	OS was determined for all participants and was defined as the time from randomization to death due to any cause. Participants were censored at the date of their last follow-up. The OS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame	Up to approximately 36.1 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	44
Median (95% Confidence Interval) [Months]	18.2	18.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4737
	Comments	P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.2145
	Confidence Interval	(2-Sided) 95%; 0.7131 to 2.0684
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.

3. Secondary Outcome

Title	Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
Description	DLTs will be evaluated during the safety run-in period. Any treatment emergent Grade 3 or higher adverse event (AE) that occurs in the first 42 days after initiation of study treatment, that is deemed possibly, probably or definitely related to the combination of CMB305 and atezolizumab will be considered a DLT with the following exceptions: Alopecia or vomiting (unless not controlled by optimal anti-emetics) Hepatic enzyme elevations associated with the baseline Grade 2 abnormalities Grade 3 laboratory AEs that are asymptomatic and return to baseline or to Grade 1 within 3 days, unless identified specifically as DLT by the investigator or the Data Monitoring Committee (DMC) Grade 3 fatigue Grade 3 systemic reactions (such as fever, headache, influenza like symptoms, myalgia, malaise, or nausea) that return to baseline or Grade 1 within 3 days of study inoculation
Time Frame	Up to approximately 42 days

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who participated in the safety run-in period and received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	6	6
Count of Participants [Participants]	1 2.2%	1 2.3%

4. Secondary Outcome

Title	Number of Participants Who Experienced At Least One Adverse Event (AE)
Description	An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Time Frame	Up to approximately 36.1 months

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	43
Count of Participants [Participants]	44 97.8%	43 97.7%

5. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Description	An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Time Frame	Up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	43
Count of Participants [Participants]	6 13.3%	6 13.6%

6. Secondary Outcome

Title	Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Participants were evaluated every 6 weeks with radiographic imaging to assess their response to treatment. The PFS rate was calculated as the percentage of participants with PFS at Month 3.
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	44
Number (95% Confidence Interval) [Percentage of participants]	32.6 72.4%	23.8 54.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3645
	Comments	P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
	Method	Log Rank
	Comments

7. Secondary Outcome

Title	Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first, per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. PD was defined as ≥20% increase in tumor burden compared with nadir (at any single time point) in 2 consecutive observations ≥4 weeks apart. If there was no disease progression or death, participants were censored at the date of their last disease assessment. The PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. Participants were evaluated every 6 weeks with radiographic imaging to assess their response to treatment. The PFS rate was calculated as the percentage of participants with PFS at Month 6.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	44
Number (95% Confidence Interval) [Percentage of participants]	16.5 36.7%	9.5 21.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3466
	Comments	P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
	Method	Log Rank
	Comments

8. Secondary Outcome

Title	Time to Next Treatment (TTNT)
Description	TTNT was the time from date of randomization to the start date of subsequent treatment. Participants were treated for up to approximately 2 years and then followed until next treatment or death. Participants who did not receive subsequent treatment were censored at the date of last contact or death. The TTNT was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame	Up to approximately 36.1 months

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	43
Median (95% Confidence Interval) [Months]	6.2	4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1622
	Comments	P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.7006
	Confidence Interval	(2-Sided) 95%; 0.4241 to 1.1574
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.

9. Secondary Outcome

Title	Distant Metastasis Free Survival (DMFS)
Description	DMFS was the time between the date of randomization and the date of first distant metastasis or date of death (whatever the cause), whichever occurs first. Participants without metastasis and death were censored at the date of last contact or death. The DMFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time Frame	Up to approximately 36.1 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	44
Median (Full Range) [Months]	5.3	5.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6397
	Comments	P-value based on a 2-sided stratified log-rank test stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.1849
	Confidence Interval	(2-Sided) 95%; 0.5817 to 2.4134
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is from Cox proportional hazards model stratified by type of sarcoma: synovial sarcoma versus myxoid/round cell liposarcoma.

10. Secondary Outcome

Title	Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody at Baseline
Description	The number of participants with anti-NY-ESO-1 antibodies at baseline was measured using an enzyme-linked immunosorbent assay (ELISA) with recombinant NY-ESO1 protein. A titer of >1:100 was considered positive. The number of participants that were anti-NY-ESO-1 antibody positive at baseline is presented.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for baseline antibody analysis.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	35	29
Count of Participants [Participants]	14 31.1%	6 13.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1128
	Comments
	Method	exact Pearson chi-square test
	Comments

11. Secondary Outcome

Title	Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody After Induction With Treatment
Description	The number of participants with anti-NY-ESO-1 antibodies induced after treatment was measured using an enzyme-linked immunosorbent assay (ELISA) with recombinant NY-ESO1protein. A titer of >1:100 was considered positive. The induction of anti-NY-ESO-1 antibody response was defined as a ≥4-fold increase in the titer or the presence of a newly positive response after the first dose of treatment. The number of participants that were anti-NY-ESO-1 antibody positive after induction with treatment is presented.
Time Frame	Up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for induction after treatment antibody analysis.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	32	27
Count of Participants [Participants]	16 35.6%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	exact Pearson chi-square test
	Comments

12. Secondary Outcome

Title	Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells at Baseline
Description	Anti-NY-ESO-1 CD4 and CD8 positive T-cell responses were measured by interferon gamma detecting enzyme-linked ImmunoSpot (ELISPOT) using isolated CD4 and CD8 positive T cells from peripheral blood mononuclear cells (PBMCs) expanded in vitro with a NY-ESO-1 peptide pool (20-mer peptides, 10-mer overlap) and considered positive if there were >50 spot-forming units/50,000 cells observed for NY-ESO-1 peptides and a ≥2-fold increase in spot-forming units compared with a negative control. The number of participants that were anti-NY-ESO-1 T cell positive at baseline is presented.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for baseline T cell analysis.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	27	24
Count of Participants [Participants]	17 37.8%	12 27.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4050
	Comments
	Method	exact Pearson chi-square test
	Comments

13. Secondary Outcome

Title	Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells After Induction With Treatment
Description	Anti-NY-ESO-1 CD4 and CD8 positive T-cell responses were measured by interferon gamma detecting enzyme-linked ImmunoSpot (ELISPOT) using isolated CD4 and CD8 positive T cells expanded with a NY-ESO-1 peptide (20-mer peptides, 10-mer overlap) and considered positive if there were >50 spot-forming units (SPU)/50,000 cells observed for NY-ESO-1 peptides and a ≥2-fold increase in SPU compared with a negative control. The induction of an anti-NYESO-1 CD4 or CD8 positive T-cell response was defined as de novo positive or ≥2-fold rise in the number of SPU after the first dose. A fluorescence-activated cell sorting (FACS)-based intracellular cytokine staining assay for interferon gamma or tumor necrosis factor alpha after stimulation with NY-ESO-1 peptide was also used and staining ≥2-fold above the baseline value was considered positive for T-cell responses. The number of participants that were anti-NY-ESO-1 T cell positive after induction with treatment is presented.
Time Frame	Up to approximately 24 months

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab and had data available for induction after treatment T cell analysis.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	26	20
Count of Participants [Participants]	14 31.1%	3 6.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab, Atezolizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0127
	Comments
	Method	exact Pearson chi-square test
	Comments

14. Other Pre-specified Outcome

Title	Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all lesions in 2 consecutive observations ≥4 weeks apart) or a Partial Response (PR: ≥30% decrease in tumor burden compared with baseline in 2 observations ≥4 weeks apart) per RECIST 1.1 modified to use irRC confirmation and unidimensional tumor measurements as assessed by BICR. Participants with missing data were considered non-responders. The percentage of participants who experienced a CR or PR is presented.
Time Frame	Up to approximately 36.1 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who met eligibility criteria for the study and had data recorded in the eCRF. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab	Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.	Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Measure Participants	45	44
Number (95% Confidence Interval) [Percentage of participants]	2.2 4.9%	0.0 0%

Adverse Events

Time Frame	Up to approximately 36.1 months
Adverse Event Reporting Description	Populations: All participants who received ≥1 dose of study treatment for AEs; all randomized participants for all-cause mortality. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study drug are excluded as AEs.
Arm/Group Title	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab		Atezolizumab
Arm/Group Description	Participants received CMB305 treatment in combination with 1200 mg/day atezolizumab administered by IV infusion Q3W for up to approximately 2 years. CMB305 treatment consisted of 2 doses of LV305 administered ID on Days 0 and 14 followed every 2 weeks with alternating doses of G305 administered IM and LV305. LV305 was administered at a dose of 1×10^10 vector genomes and G305 at a dose of 5 mcg glucopyranosyl lipid A stable emulsion mixed with 250 mcg of NY ESO-1 protein.		Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
All Cause Mortality
	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab		Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/45 (68.9%)		27/44 (61.4%)
Serious Adverse Events
	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab		Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/45 (37.8%)		9/43 (20.9%)
Cardiac disorders
Acute left ventricular failure	1/45 (2.2%)	2	0/43 (0%)	0
Atrial fibrillation	1/45 (2.2%)	1	0/43 (0%)	0
Pericardial effusion	1/45 (2.2%)	1	0/43 (0%)	0
Congenital, familial and genetic disorders
Right ventricle outflow tract obstruction	1/45 (2.2%)	1	0/43 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/45 (4.4%)	2	0/43 (0%)	0
Nausea	1/45 (2.2%)	1	0/43 (0%)	0
Small intestinal haemorrhage	1/45 (2.2%)	1	0/43 (0%)	0
General disorders
Chest pain	1/45 (2.2%)	1	0/43 (0%)	0
Influenza like illness	1/45 (2.2%)	1	1/43 (2.3%)	1
Pyrexia	1/45 (2.2%)	1	0/43 (0%)	0
Immune system disorders
Drug hypersensitivity	1/45 (2.2%)	1	0/43 (0%)	0
Infections and infestations
Influenza	1/45 (2.2%)	1	0/43 (0%)	0
Pneumonia	3/45 (6.7%)	3	0/43 (0%)	0
Pyelonephritis	1/45 (2.2%)	1	0/43 (0%)	0
Sepsis	1/45 (2.2%)	1	0/43 (0%)	0
Staphylococcal bacteraemia	1/45 (2.2%)	1	0/43 (0%)	0
Urinary tract infection	0/45 (0%)	0	1/43 (2.3%)	1
Injury, poisoning and procedural complications
Spinal compression fracture	1/45 (2.2%)	1	0/43 (0%)	0
Metabolism and nutrition disorders
Hypervolaemia	0/45 (0%)	0	1/43 (2.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage	1/45 (2.2%)	1	0/43 (0%)	0
Nervous system disorders
Hypoaesthesia	0/45 (0%)	0	1/43 (2.3%)	1
Spinal cord compression	0/45 (0%)	0	4/43 (9.3%)	4
Renal and urinary disorders
Urinary tract obstruction	1/45 (2.2%)	1	0/43 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/45 (2.2%)	1	0/43 (0%)	0
Dyspnoea	1/45 (2.2%)	1	1/43 (2.3%)	1
Haemoptysis	3/45 (6.7%)	3	1/43 (2.3%)	1
Pneumonia aspiration	1/45 (2.2%)	1	0/43 (0%)	0
Pneumonitis	2/45 (4.4%)	3	0/43 (0%)	0
Pneumothorax	1/45 (2.2%)	2	0/43 (0%)	0
Respiratory failure	1/45 (2.2%)	1	0/43 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulcer	0/45 (0%)	0	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab		Atezolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/45 (93.3%)		42/43 (97.7%)
Blood and lymphatic system disorders
Anaemia	4/45 (8.9%)	6	6/43 (14%)	7
Lymphadenopathy	3/45 (6.7%)	3	0/43 (0%)	0
Cardiac disorders
Sinus tachycardia	3/45 (6.7%)	3	1/43 (2.3%)	1
Gastrointestinal disorders
Constipation	9/45 (20%)	10	5/43 (11.6%)	6
Diarrhoea	12/45 (26.7%)	15	7/43 (16.3%)	11
Nausea	12/45 (26.7%)	15	11/43 (25.6%)	12
Vomiting	5/45 (11.1%)	7	7/43 (16.3%)	7
General disorders
Chest pain	4/45 (8.9%)	4	2/43 (4.7%)	2
Chills	3/45 (6.7%)	3	2/43 (4.7%)	2
Fatigue	18/45 (40%)	31	10/43 (23.3%)	11
Influenza like illness	3/45 (6.7%)	4	3/43 (7%)	4
Injection site pain	5/45 (11.1%)	5	0/43 (0%)	0
Injection site reaction	3/45 (6.7%)	3	0/43 (0%)	0
Pyrexia	7/45 (15.6%)	8	6/43 (14%)	7
Infections and infestations
Upper respiratory tract infection	3/45 (6.7%)	3	2/43 (4.7%)	2
Urinary tract infection	3/45 (6.7%)	3	0/43 (0%)	0
Injury, poisoning and procedural complications
Procedural pain	2/45 (4.4%)	2	6/43 (14%)	7
Investigations
Activated partial thromboplastin time prolonged	4/45 (8.9%)	10	3/43 (7%)	3
Alanine aminotransferase increased	3/45 (6.7%)	5	4/43 (9.3%)	5
Aspartate aminotransferase increased	3/45 (6.7%)	6	3/43 (7%)	3
Blood alkaline phosphatase increased	4/45 (8.9%)	9	4/43 (9.3%)	5
Blood lactate dehydrogenase increased	3/45 (6.7%)	3	2/43 (4.7%)	2
Metabolism and nutrition disorders
Decreased appetite	6/45 (13.3%)	8	2/43 (4.7%)	3
Hyperglycaemia	3/45 (6.7%)	4	5/43 (11.6%)	7
Hypocalcaemia	4/45 (8.9%)	6	2/43 (4.7%)	2
Hypokalaemia	4/45 (8.9%)	9	3/43 (7%)	3
Hyponatraemia	0/45 (0%)	0	3/43 (7%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	4/45 (8.9%)	4	6/43 (14%)	7
Back pain	9/45 (20%)	12	4/43 (9.3%)	5
Musculoskeletal pain	0/45 (0%)	0	3/43 (7%)	3
Neck pain	3/45 (6.7%)	3	2/43 (4.7%)	4
Pain in extremity	5/45 (11.1%)	5	6/43 (14%)	8
Nervous system disorders
Headache	6/45 (13.3%)	7	7/43 (16.3%)	7
Neuralgia	1/45 (2.2%)	1	4/43 (9.3%)	4
Psychiatric disorders
Insomnia	4/45 (8.9%)	4	3/43 (7%)	3
Renal and urinary disorders
Acute kidney injury	3/45 (6.7%)	3	0/43 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	8/45 (17.8%)	11	5/43 (11.6%)	6
Dyspnoea	12/45 (26.7%)	15	3/43 (7%)	3
Haemoptysis	5/45 (11.1%)	6	2/43 (4.7%)	3
Oropharyngeal pain	3/45 (6.7%)	3	1/43 (2.3%)	1
Pleuritic pain	3/45 (6.7%)	3	0/43 (0%)	0
Pneumothorax	0/45 (0%)	0	3/43 (7%)	3
Skin and subcutaneous tissue disorders
Dry skin	6/45 (13.3%)	6	0/43 (0%)	0
Pruritus	5/45 (11.1%)	6	2/43 (4.7%)	2
Rash pruritic	1/45 (2.2%)	1	3/43 (7%)	3
Vascular disorders
Hypertension	5/45 (11.1%)	8	5/43 (11.6%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Manuscripts reporting the results of this clinical trial, abstracts, press releases, and other media presentations must be provided to the Sponsor for review and comment 30 days prior to submission for publication and may be delayed for up to an additional 30 days in order to ensure that confidential and proprietary data, and intellectual property rights, are protected. Co-authorship of publications will be discussed and mutually agreed upon before submission of a manuscript to a publisher.