Back to resultsStudy to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
Primary Purpose
Sarcoma, Myxoid/Round Cell Liposarcoma, Synovial Sarcoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CMB305
atezolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoma focused on measuring immunotherapy, CMB305, LV305, GLA-SE, atezolizumab, NY-ESO-1
Eligibility Criteria
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
Sites / Locations
- Stanford University Medical Center
- Sarcoma Oncology Research Center
- University of Colorado Cancer Center
- MedStar Washington Hospital Center
- Mayo Clinic of Jacksonville
- Georgia Cancer Specialists
- Northwestern University Feinburg School of Medicine
- University of Iowa Hospital and Clinics
- Massachusetts General Hospital
- Mayo Clinic Rochester
- Washington University in St. Louis
- Monter Cancer Research
- Levine Cancer Institute
- Duke Cancer Institute
- Fox Chase cancer Center
- Vanderbilt University
- University of Vermont Cancer Center
- Scca/Fhcrc
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
CMB305 (sequentially administered LV305 and G305)+Atezolizumab
Atezolizumab
Arm 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 NY ESO-1 protein.
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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.
Overall Survival (OS)
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
Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
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
Number of Participants Who Experienced At Least One Adverse Event (AE)
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.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
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.
Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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.
Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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 to Next Treatment (TTNT)
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.
Distant Metastasis Free Survival (DMFS)
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.
Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody at Baseline
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.
Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody After Induction With Treatment
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.
Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells at Baseline
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.
Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells After Induction With Treatment
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.
Full Information
NCT ID
NCT02609984
First Posted
November 14, 2015
Last Updated
June 26, 2020
Sponsor
Immune Design
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02609984
Brief Title
Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
This study did not meet the efficacy objective
Study Start Date
April 29, 2015 (Actual)
Primary Completion Date
February 6, 2019 (Actual)
Study Completion Date
February 6, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Immune Design
Collaborators
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Myxoid/Round Cell Liposarcoma, Synovial Sarcoma, Metastatic Sarcoma, Recurrent Adult Soft Tissue Sarcoma, Locally Advanced Sarcoma, Liposarcoma
Keywords
immunotherapy, CMB305, LV305, GLA-SE, atezolizumab, NY-ESO-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
89 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CMB305 (sequentially administered LV305 and G305)+Atezolizumab
Arm Type
Experimental
Arm 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 NY ESO-1 protein.
Arm Title
Atezolizumab
Arm Type
Active Comparator
Arm Description
Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years.
Intervention Type
Biological
Intervention Name(s)
CMB305
Intervention Description
A combination of LV305 administered intradermally (ID) and G305 administered intramuscularly (IM)
Intervention Type
Biological
Intervention Name(s)
atezolizumab
Other Intervention Name(s)
TECENTRIQ®
Intervention Description
IV Infusion
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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)
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
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)
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
Other Pre-specified Outcome Measures:
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Sarcoma Oncology Research Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
MedStar Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Mayo Clinic of Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Georgia Cancer Specialists
City
Sandy Springs
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Northwestern University Feinburg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Iowa Hospital and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
10029
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Monter Cancer Research
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke Cancer Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Fox Chase cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Vermont Cancer Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
Scca/Fhcrc
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34260265
Citation
Chawla SP, Van Tine BA, Pollack SM, Ganjoo KN, Elias AD, Riedel RF, Attia S, Choy E, Okuno SH, Agulnik M, von Mehren M, Livingston MB, Keedy VL, Verschraegen CF, Philip T, Bohac GC, Yurasov S, Yakovich A, Lu H, Chen M, Maki RG. Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1. J Clin Oncol. 2022 Apr 20;40(12):1291-1300. doi: 10.1200/JCO.20.03452. Epub 2021 Jul 14.
Results Reference
derived
Learn more about this trial
Study to Compare the Safety and Efficacy of CMB305 With Atezolizumab to Atezolizumab Alone in Participants With Sarcoma (IMDZ-C232/V943A-002)
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