Liposarcoma, Locally Advanced Sarcoma, Metastatic Sarcoma, Myxoid/Round Cell Liposarcoma, Recurrent Adult Soft Tissue Sarcoma, Sarcoma, Synovial Sarcoma
Conditions
Keywords
immunotherapy, CMB305, LV305, GLA-SE, atezolizumab, NY-ESO-1
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.
Interventions
BIOLOGICALCMB305
A combination of LV305 administered intradermally (ID) and G305 administered intramuscularly (IM)
BIOLOGICALatezolizumab
IV Infusion
Sponsors
Genentech, Inc.
Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab 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. | 45 |
| Atezolizumab Participants received 1200 mg/day atezolizumab by IV infusion Q3W for up to approximately 2 years. | 44 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 29 | 26 |
| Overall Study | Disease Progression | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Participation Discontinued by Sponsor | 12 | 10 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Atezolizumab |
|---|---|---|---|
| Age, Continuous | 46.4 Years STANDARD_DEVIATION 15.27 | 46.2 Years STANDARD_DEVIATION 16.52 | 46.7 Years STANDARD_DEVIATION 14.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants | 37 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 73 Participants | 35 Participants | 38 Participants |
| Sex: Female, Male Female | 38 Participants | 19 Participants | 19 Participants |
| Sex: Female, Male Male | 51 Participants | 26 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 31 / 45 | 27 / 44 |
| other Total, other adverse events | 42 / 45 | 42 / 43 |
| serious Total, serious adverse events | 17 / 45 | 9 / 43 |
Outcome results
Primary
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.
Time frame: Up to approximately 36.1 months
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Overall Survival (OS) | 18.2 Months |
| Atezolizumab | Overall Survival (OS) | 18.0 Months |
p-value: 0.473795% CI: [0.7131, 2.0684]Log Rank
Primary
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.
Time frame: Up to approximately 36.1 months
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 2.6 Months |
| Atezolizumab | Progression-Free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 1.6 Months |
p-value: 0.4995% CI: [0.5507, 1.333]Log Rank
Secondary
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.
Time frame: Up to approximately 36.1 months
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Distant Metastasis Free Survival (DMFS) | 5.3 Months |
| Atezolizumab | Distant Metastasis Free Survival (DMFS) | 5.5 Months |
p-value: 0.639795% CI: [0.5817, 2.4134]Log Rank
Secondary
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
Time frame: Up to approximately 42 days
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Atezolizumab | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) | 1 Participants |
Secondary
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.
Time frame: Up to approximately 24 months
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody After Induction With Treatment | 16 Participants |
| Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody After Induction With Treatment | 0 Participants |
p-value: <0.0001exact Pearson chi-square test
Secondary
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.
Time frame: Baseline (Day 1)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody at Baseline | 14 Participants |
| Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) Antibody at Baseline | 6 Participants |
p-value: 0.1128exact Pearson chi-square test
Secondary
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.
Time frame: Up to approximately 24 months
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells After Induction With Treatment | 14 Participants |
| Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells After Induction With Treatment | 3 Participants |
p-value: 0.0127exact Pearson chi-square test
Secondary
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.
Time frame: Baseline (Day 1)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells at Baseline | 17 Participants |
| Atezolizumab | Number of Participants Positive for Anti-New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) T Cells at Baseline | 12 Participants |
p-value: 0.405exact Pearson chi-square test
Secondary
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.
Time frame: Up to approximately 24 months
Population: The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 6 Participants |
| Atezolizumab | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 6 Participants |
Secondary
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.
Time frame: Up to approximately 36.1 months
Population: The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Number of Participants Who Experienced At Least One Adverse Event (AE) | 44 Participants |
| Atezolizumab | Number of Participants Who Experienced At Least One Adverse Event (AE) | 43 Participants |
Secondary
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.
Time frame: Month 3
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 32.6 Percentage of participants |
| Atezolizumab | Progression-Free Survival (PFS) Rate at Month 3 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 23.8 Percentage of participants |
p-value: 0.3645Log Rank
Secondary
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 frame: Month 6
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 16.5 Percentage of participants |
| Atezolizumab | Progression-Free Survival (PFS) Rate at Month 6 Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 9.5 Percentage of participants |
p-value: 0.3466Log Rank
Secondary
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.
Time frame: Up to approximately 36.1 months
Population: The analysis population included all participants who received ≥1 dose of any of the CMB305 components (LV305, G305) or atezolizumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Time to Next Treatment (TTNT) | 6.2 Months |
| Atezolizumab | Time to Next Treatment (TTNT) | 4.9 Months |
p-value: 0.162295% CI: [0.4241, 1.1574]Log Rank
Other Pre-specified
Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| CMB305 (Sequentially Administered LV305 and G305)+Atezolizumab | Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 2.2 Percentage of participants |
| Atezolizumab | Overall Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 0.0 Percentage of participants |