A Study Evaluating the Efficacy and Safety of Multiple Tr... | NCT05116202 | Trialant
NCT05116202
Sponsor
Hoffmann-La Roche
Status
Completed
Last Update Posted
Jul 18, 2025Actual
Enrollment
110Actual
Phase
Phase 1Phase 2
Conditions
Melanoma
Interventions
Nivolumab
Ipilimumab
RO7247669 2100 mg
Atezolizumab
Tiragolumab
RO7247669 600 mg
Countries
United States
Australia
France
Italy
Spain
Protocol Section
Identification Module
NCT ID
NCT05116202
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
BO43328
Secondary IDs
Not provided
Brief Title
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
Official Title
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)
Acronym
Not provided
Organization
Hoffmann-La RocheINDUSTRY
Status Module
Record Verification Date
Jun 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 2, 2022Actual
Primary Completion Date
Sep 22, 2023Actual
Completion Date
May 28, 2024Actual
First Submitted Date
Oct 22, 2021
First Submission Date that Met QC Criteria
Nov 2, 2021
First Posted Date
Nov 10, 2021Actual
Results Waived
Not provided
Results First Submitted Date
May 21, 2025
Results First Submitted that Met QC Criteria
Jun 30, 2025
Results First Posted Date
Jul 18, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Sep 17, 2024
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Jul 18, 2025Actual
Last Update Submitted Date
Jun 30, 2025
Last Update Posted Date
Jul 18, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Hoffmann-La RocheINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Not provided
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of treatment combinations in cancer immunotherapy (CIT)-naive participants with resectable Stage III melanoma (Cohort 1) and in participants with Stage IV melanoma (Cohort 2). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population.
Detailed Description
Not provided
Conditions Module
Conditions
Melanoma
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
110Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1: Nivolumab + Ipilimumab
Active Comparator
Cohort 1 participants in the nivolumab plus ipilimumab arm will receive treatment for 2 cycles (6 weeks) on Day 1 of each cycle (cycle length 21 days) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
Drug: Nivolumab
Drug: Ipilimumab
Cohort 1: RO7247669 2100 mg
Experimental
Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
Drug: RO7247669 2100 mg
Cohort 1: + Atezolizumab + Tiragolumab
Experimental
Cohort 1 participants in the atezolizumab plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
Drug: Atezolizumab
Drug: Tiragolumab
Cohort 1: RO7247669 2100 mg + Tiragolumab
Experimental
Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
Drug: RO7247669 2100 mg
Drug: Tiragolumab
Cohort 2: RO7247669 2100 mg + Tiragolumab
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Nivolumab
Drug
Nivolumab will be administered at a dose of 3 mg/kg IV on Day 1 of each 21 day cycle.
Cohort 1: Nivolumab + Ipilimumab
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review
pRR was defined as the percentage of participants with pathologic complete response (pCR), pathologic near complete response (pnCR), and pathologic partial response (pPR) as determined by an independent pathologic review. pCR was defined as a complete absence of viable tumor cells, pnCR as > 0 to ≤ 10% of viable tumor cells, and pPR was defined as > 10 to ≤ 50% of viable tumor cells in the dissected lymph node. Participants with missing or no pathologic response assessment, including participants who did not proceed to complete lymph node dissection (CLND), were classified as non-responders. pRR was calculated for each arm along with 95% confidence intervals (CIs) using Clopper-Pearson method. The difference in pRR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Time of surgery (scheduled at Week 7)
Objective Response Rate (ORR) for Cohort 2 as Determined by the Investigator
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. ORR was calculated for each arm, along with 95% CIs using Clopper-Pearson method.
From randomization up to approximately 3.6 months
Secondary Outcomes
Measure
Description
Time Frame
pRR for Cohort 1 as Determined by Local Pathologic Assessment
pRR was defined as the percentage of participants with pCR, pnCR, and pPR as determined by a local pathologic review. pCR was defined as a complete absence of viable tumor cells, pnCR as > 0 to ≤ 10% of viable tumor cells, and pPR was defined as > 10 to ≤ 50% of viable tumor cells in the dissected lymph node. Participants with missing or no pathologic response assessment, including participants who did not proceed to CLND, were classified as non-responders. pRR was calculated for each arm along with 95% CIs using Clopper-Pearson method. The difference in pRR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria for Cohort 1:
ECOG performance status (PS) of 0 or 1
Histologically confirmed resectable Stage III melanoma according to AJCC-8 and no history of in-transit metastases within the last 6 months
Fit and planned for CLND
Measurable disease according to RECIST v1.1
Availability of a representative tumor specimen
Adequate hematologic and end-organ function
For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
Negative HIV test, negative hepatitis B surface antibody (HBsAb), and negative total hepatitis B core antibody (HBcAb) test, and negative hepatitis C virus (HCV) at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load.
Exclusion Criteria for Cohort 1:
Mucosal, uveal and acral lentiginous melanoma
Distantly metastasized melanoma
History of in-transit metastases within the last 6 months
Prior radiotherapy
Prior immunotherapy, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, and other systemic therapy for melanoma
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
Prior allogeneic stem cell or solid organ transplantation
Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication, or anticipation of need for systemic immunosuppressant medication during study treatment
Active or history of autoimmune disease or immune deficiency
Inclusion Criteria for Cohort 2:
ECOG PS of 0 or 1
Life expectancy >= 3 months, as determined by the investigator
Histologically confirmed Stage IV (metastatic) cutaneous melanoma according to AJCC-8
Disease progression during or following at least one but no more than two lines of treatment for metastatic disease
Measurable disease according to RECIST v1.1
Availability of a representative tumor specimen
Adequate hematologic and end-organ function
For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
Negative HIV test, negative hepatitis B surface antibody (HBsAb), and negative total hepatitis B core antibody (HBcAb) test, and negative hepatitis C virus (HCV) at screening. Patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load.
Exclusion Criteria for Cohort 2:
Mucosal and uveal melanoma
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
Prior allogeneic stem cell or solid organ transplantation
Known immunodeficiency or conditions requiring treatment with systemic immunosuppressive medication, or anticipation of need for systemic immunosuppressant medication during study treatment
Active or history of autoimmune disease or immune deficiency
Symptomatic, untreated, or progressing CNS metastases
Active or history of carcinomatous meningitis/leptomeningeal disease
Long GV, Nair N, Marbach D, Scolyer RA, Wilson S, Cotting D, Staedler N, Amaria RN, Ascierto PA, Tarhini AA, Robert C, Hamid O, Gaudy-Marqueste C, Lebbe C, Munoz-Couselo E, Menzies AM, Pages C, Curigliano G, Mandala M, Jessop N, Bader U, Perdicchio M, Teichgraber V, Muecke M, Markert C, Blank C. Neoadjuvant PD-1 and LAG-3-targeting bispecific antibody and other immune checkpoint inhibitor combinations in resectable melanoma: the randomized phase 1b/2 Morpheus-Melanoma trial. Nat Med. 2025 Nov;31(11):3700-3712. doi: 10.1038/s41591-025-03967-2. Epub 2025 Sep 24.
A total of 110 participants with resectable Stage III melanoma and Stage IV melanoma took part in Cohort 1 and Cohort 2, respectively. A total of 6 treatment arms were planned in Cohort 1 and 102 participants were enrolled in only 4 arms. The study was closed before the Cohort 1 arms tobemstomig 600 milligrams (mg), and tobemstomig 600 mg + tiragolumab were opened. 8 participants were enrolled in 1 arm in Cohort 2.
Recruitment Details
Participants took part in the study across 14 investigative sites in 5 countries: the United States, Italy, France, Spain, and Australia.
The study is considered "Completed" because all the pre-planned study activities and analyses have been performed.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 milligrams/kilograms (mg/kg) intravenously (IV) and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP
Yes
Yes
No
Study Protocol and Statistical Analysis Plan
May 8, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Netherlands
Submission Tracking
Estimated Results First Submitted Date
Not provided
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Experimental
Cohort 2 participants in RO7247669 plus tiragolumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Drug: RO7247669 2100 mg
Drug: Tiragolumab
Cohort 1: RO7247669 600 mg
Experimental
Cohort 1 participants in the RO7247669 arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
Drug: RO7247669 600 mg
Cohort 1: RO7247669 600 mg + Tiragolumab
Experimental
Cohort 1 participants in the RO7247669 plus tiragolumab arm will receive treatment for 2 cycles (6 weeks) until surgery, or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
Drug: Tiragolumab
Drug: RO7247669 600 mg
Ipilimumab
Drug
Ipilimumab will be administered at a dose of 1 mg/kg by IV on Day 1 of each 21 day cycle.
Cohort 1: Nivolumab + Ipilimumab
RO7247669 2100 mg
Drug
RO7247669 will be administered at a dose of 2100 mg by IV infusion on Day 1 of each 21 day cycle.
Cohort 1: RO7247669 2100 mg
Cohort 1: RO7247669 2100 mg + Tiragolumab
Cohort 2: RO7247669 2100 mg + Tiragolumab
Atezolizumab
Drug
Atezolizumab will be administered at a dose of 1200 mg IV on Day 1 of each 21 day cycle.
Cohort 1: + Atezolizumab + Tiragolumab
Tecentriq, RO5541267
Tiragolumab
Drug
Tiragolumab will be administered at a dose of 600 mg IV on Day 1 of each 21 day cycle.
Cohort 1: + Atezolizumab + Tiragolumab
Cohort 1: RO7247669 2100 mg + Tiragolumab
Cohort 1: RO7247669 600 mg + Tiragolumab
Cohort 2: RO7247669 2100 mg + Tiragolumab
RO7092284
RO7247669 600 mg
Drug
RO7247669 will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.
Cohort 1: RO7247669 600 mg
Cohort 1: RO7247669 600 mg + Tiragolumab
Time of surgery ( scheduled at Week 7)
Event-free Survival (EFS) for Cohort 1
EFS was defined as the time from randomization to any of the following events (whichever occurs first): documented disease progression (PD) that precludes surgery, as assessed by investigator per RECIST v1.1, local, regional, or distant disease recurrence, or death from any cause. PD = as at least a 20% increase in smallest sum of diameter (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Local recurrence was defined as tumor regrowth within 2 cm of the primary lesion's tumor bed; regional recurrence as any nodal or non-nodal tumor lesions that are > 2 cm from the primary lesion but not beyond the regional nodal basin; distant recurrence as any non-local/non-regional recurrence. Participants without disease recurrence, progression, or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier method was used to estimate the median for EFS, and 95% CIs was constructed using Brookmeyer and Crowley method.
From randomization to disease progression, disease recurrence or death or last tumor assessment (up to 22.51 months)
Relapse-free Survival (RFS) for Cohort 1
RFS was defined as the time from surgery to the first documented recurrence of disease or death from any cause. Recurrent disease includes local, regional, or distant recurrence: local recurrence was defined as tumor regrowth within 2 cm of the primary lesion's tumor bed; regional recurrence as any nodal or non-nodal tumor lesions that are more than 2 cm from the primary lesion but are not beyond the regional nodal basin; distant recurrence as any non-local/non-regional recurrence. Participants without disease recurrence or death at the time of analysis were censored at the last tumor assessment. Kaplan-Meier method was used to estimate the median for RFS, and 95% CIs were constructed using the Brookmeyer and Crowley method.
From surgery (scheduled at Week 7) to first documented disease recurrence or death or last tumor assessment (up to 20.9 months)
Overall Survival (OS) for Cohort 1
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. Kaplan-Meier method was used to estimate the median for OS, 95% CIs were constructed using the Brookmeyer and Crowley method.
From randomization to death from any cause or last known to be alive (Up to 25 months)
ORR for Cohort 1
ORR was defined as the percentage of participants with a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. ORR was calculated for each arm, along with 95% CIs using the Clopper-Pearson method. The difference in ORR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Prior to surgery (up to Week 6)
Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) for Cohort 1
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. Severity was determined per NCI CTCAE v5.0 Grade 1: Mild; asymptomatic or mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2:Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant, but not immediately life-threatening: hospitalization or prolongation of hospitalization indicated; disabling or limiting self-care ADL; Grade 4: Life-threatening consequences or urgent intervention indicated; Grade 5: Death related to AE. Multiple occurrences of AEs in the same category at the worst (highest) NCIC-CTCAE grade for an individual are counted only once.
From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (Up to 5.6 months)
Number of Participants With Immune-related AEs Grade ≥ 3 for Cohort 1
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. Participants with immune-related adverse events Grade ≥ 3 were reported.
From initiation of study treatment up to 135 days after the final dose of study treatment (Up to 5.6 months)
Rate of Delayed Surgery Due to Treatment-related AEs
Rate of delayed surgery due to treatment related AEs was defined as the percentage of participants for whom surgery was delayed due to treatment-related AEs for more than 2 weeks. An AE was any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of the investigational product, whether considered related to the investigational product.
Time of surgery (scheduled at Week 7) up to 40.1 weeks
Duration of Surgery Delay Due to Treatment-related AEs
Duration of surgery delay due to treatment related AEs was calculated on the participants for whom surgery was delayed due to treatment-related AEs for more than 2 weeks. An AE was any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of the investigational product, whether considered related to the investigational product.
Time of surgery (scheduled at Week 7) up to 40.1 weeks
Surgical Complication Rates for Cohort 1
Surgical complications were scored according to the Clavien-Dindo surgical classification. Complication rates for every grade were reported and scored for participants who underwent CLND. The Surgical complications according to Clavien-Dindo can be classified into the following grades: Grade I: Any complication that does not need pharmacological treatment or surgical, endoscopic, and radiological interventions. Grade II: Complications that require pharmacological treatment with drugs or blood transfusions and total parenteral nutrition. Grade III: Complications that require surgical, endoscopic, or radiological intervention with (Grade IIIb) or without (Grade IIIa) general anesthesia. Grade IV: Life-threatening complications requiring intensive care unit (ICU) management, which may be single organ (Grade IVa) or multiorgan (Grade IVb) dysfunction. Grade V: Complications that might cause the death of a participant. Values have been rounded off to 2 decimal digits.
At treatment discontinuation visit (Week 13) and Surgery Follow-Up (6 months after surgery)
Progression-Free Survival (PFS) for Cohort 2
PFS after randomization/enrollment was defined as the time from randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurred first), as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on the study (including baseline) and/or unequivocal progression of a non-target lesion and/or any new lesion. Participants without documented disease progression or death at the time of analysis were censored at the day of the last tumor assessment. Kaplan-Meier method was used to estimate the median for PFS, with 95% CIs constructed by using the Brookmeyer and Crowley method.
From randomization/enrollment to first documented disease progression or death or last tumor assessment (up to 3.6 months)
OS for Cohort 2
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. Kaplan-Meier method was used to estimate the median for OS, with 95% CIs constructed by using the Brookmeyer and Crowley method.
From randomization/enrollment to death from any cause or last known to be alive (Up to 24.2 months)
OS Rates at Specific Timepoints for Cohort 2
OS was defined as the time from randomization to death from any cause. OS rate is percentage of participants who were event free for OS. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. OS rate at specific time points were estimated using the Kaplan-Meier method, with 95% CIs calculated based on Greenwood's estimate for the variance.
Months 3, 6 and 12
Duration of Response (DOR) for Cohort 2
DOR was defined as the time from the first occurrence of a documented objective response (OR) to disease progression or death from any cause (whichever occurred first), as determined by the investigator according to RECIST v1.1. OR was defined as a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR = at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on the study (including baseline). Participants without PD or death at time of analysis were censored at time of last tumor assessment. Kaplan-Meier method was used to estimate median for DOR, with 95% CIs constructed using Brookmeyer & Crowley method.
Time from the first occurrence of a documented OR to disease progression or death from any cause (up to 3.6 months)
Disease Control Rate (DCR) for Cohort 2
DCR was defined as the percentage of participants with stable disease for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Stable disease was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on the study (including baseline). DCR was calculated for each treatment arm, with 95% CIs estimated through use of Clopper-Pearson's exact method.
From randomization up to 3.6 months
Number of Participants With AEs and Severity of AEs Determined According to NCI CTCAE v5.0 for Cohort 2
An AE=any untoward medical occurrence in clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. AE can therefore be any unfavorable & unintended sign, symptom/disease temporally associated with using an investigational product, whether or not considered related to the investigational product. Severity was determined per NCI CTCAE v5.0 Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care ADL; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE. Multiple occurrences of AEs in 1 individual are counted once at highest grade.
From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (Up to 10 months)
Los Angeles
California
90025
United States
Moffitt Cancer Center
Tampa
Florida
33612
United States
MD Anderson Cancer Center
Houston
Texas
77030
United States
Melanoma Institute Australia
North Sydney
New South Wales
2060
Australia
Hopital de la Timone
Marseille
13005
France
APHP - Hospital Saint Louis
Paris
75475
France
Institut Universitaire du Cancer de Toulouse-Oncopole
Toulouse
31059
France
Institut Gustave Roussy
Villejuif
94805
France
Azienda Ospedaliera Universitaria Senese
Siena
Abruzzo
53100
Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Naples
Campania
80131
Italy
Istituto Europeo Di Oncologia
Milan
Lombardy
20141
Italy
Ospedale S.Maria della Misericordia
Perugia
Umbria
06132
Italy
Hospital Universitario Vall d Hebron
Barcelona
08035
Spain
FG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
FG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
FG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
FG004
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
FG00022 subjects
FG00140 subjects
FG00220 subjects
FG00320 subjects
FG0048 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
NOT COMPLETED
FG00022 subjects
FG00140 subjects
FG00220 subjects
FG00320 subjects
FG0048 subjects
Type
Comment
Reasons
Study Terminated by Sponsor
FG00021 subjects
FG00138 subjects
FG00217 subjects
FG00318 subjects
FG0040 subjects
Withdrawal by Subject
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0031 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Death
FG0001 subjects
FG0011 subjects
FG0022 subjects
FG0031 subjects
FG004
Intent-to-treat (ITT) population included all participants who were enrolled in the study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
BG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
BG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
BG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
BG004
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00022
BG00140
BG00220
BG00320
BG0048
BG005110
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00055.05± 16.03
BG00164.10± 10.97
BG00258.90± 14.10
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00011
BG0019
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Pathologic Response Rate (pRR) for Cohort 1 as Determined by Independent Pathologic Review
pRR was defined as the percentage of participants with pathologic complete response (pCR), pathologic near complete response (pnCR), and pathologic partial response (pPR) as determined by an independent pathologic review. pCR was defined as a complete absence of viable tumor cells, pnCR as > 0 to ≤ 10% of viable tumor cells, and pPR was defined as > 10 to ≤ 50% of viable tumor cells in the dissected lymph node. Participants with missing or no pathologic response assessment, including participants who did not proceed to complete lymph node dissection (CLND), were classified as non-responders. pRR was calculated for each arm along with 95% confidence intervals (CIs) using Clopper-Pearson method. The difference in pRR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Efficacy-evaluable population included all participants in Cohort 1 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Number
95% Confidence Interval
percentage of participants
Time of surgery (scheduled at Week 7)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG003
Title
Denominators
Categories
Title
Measurements
OG00077.3(54.63 to 92.18)
OG00180.0(64.35 to 90.95)
OG00245.0(23.06 to 68.47)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference in pRR
2.73
2-Sided
95
-22.25
27.70
Superiority
OG000
OG002
Primary
Objective Response Rate (ORR) for Cohort 2 as Determined by the Investigator
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. ORR was calculated for each arm, along with 95% CIs using Clopper-Pearson method.
Efficacy-evaluable population included all participants in Cohort 2 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Number
95% Confidence Interval
percentage of participants
From randomization up to approximately 3.6 months
ID
Title
Description
OG000
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Secondary
pRR for Cohort 1 as Determined by Local Pathologic Assessment
pRR was defined as the percentage of participants with pCR, pnCR, and pPR as determined by a local pathologic review. pCR was defined as a complete absence of viable tumor cells, pnCR as > 0 to ≤ 10% of viable tumor cells, and pPR was defined as > 10 to ≤ 50% of viable tumor cells in the dissected lymph node. Participants with missing or no pathologic response assessment, including participants who did not proceed to CLND, were classified as non-responders. pRR was calculated for each arm along with 95% CIs using Clopper-Pearson method. The difference in pRR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Efficacy-evaluable population included all participants in Cohort 1 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Number
95% Confidence Interval
percentage of participants
Time of surgery ( scheduled at Week 7)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Secondary
Event-free Survival (EFS) for Cohort 1
EFS was defined as the time from randomization to any of the following events (whichever occurs first): documented disease progression (PD) that precludes surgery, as assessed by investigator per RECIST v1.1, local, regional, or distant disease recurrence, or death from any cause. PD = as at least a 20% increase in smallest sum of diameter (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Local recurrence was defined as tumor regrowth within 2 cm of the primary lesion's tumor bed; regional recurrence as any nodal or non-nodal tumor lesions that are > 2 cm from the primary lesion but not beyond the regional nodal basin; distant recurrence as any non-local/non-regional recurrence. Participants without disease recurrence, progression, or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier method was used to estimate the median for EFS, and 95% CIs was constructed using Brookmeyer and Crowley method.
Efficacy-evaluable population included all participants in Cohort 1 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Median
95% Confidence Interval
months
From randomization to disease progression, disease recurrence or death or last tumor assessment (up to 22.51 months)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Secondary
Relapse-free Survival (RFS) for Cohort 1
RFS was defined as the time from surgery to the first documented recurrence of disease or death from any cause. Recurrent disease includes local, regional, or distant recurrence: local recurrence was defined as tumor regrowth within 2 cm of the primary lesion's tumor bed; regional recurrence as any nodal or non-nodal tumor lesions that are more than 2 cm from the primary lesion but are not beyond the regional nodal basin; distant recurrence as any non-local/non-regional recurrence. Participants without disease recurrence or death at the time of analysis were censored at the last tumor assessment. Kaplan-Meier method was used to estimate the median for RFS, and 95% CIs were constructed using the Brookmeyer and Crowley method.
Adjuvant evaluable population included participants in Cohort 1 who had completed surgery (CLND).
Posted
Median
95% Confidence Interval
months
From surgery (scheduled at Week 7) to first documented disease recurrence or death or last tumor assessment (up to 20.9 months)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Secondary
Overall Survival (OS) for Cohort 1
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. Kaplan-Meier method was used to estimate the median for OS, 95% CIs were constructed using the Brookmeyer and Crowley method.
Efficacy-evaluable population included all participants in Cohort 1 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Median
95% Confidence Interval
months
From randomization to death from any cause or last known to be alive (Up to 25 months)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Secondary
ORR for Cohort 1
ORR was defined as the percentage of participants with a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. ORR was calculated for each arm, along with 95% CIs using the Clopper-Pearson method. The difference in ORR between the experimental arms and the control arm was calculated, along with 95% CIs using the Wald method with continuity correction.
Efficacy-evaluable population included all participants in Cohort 1 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Number
95% Confidence Interval
percentage of participants
Prior to surgery (up to Week 6)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Secondary
Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) for Cohort 1
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. Severity was determined per NCI CTCAE v5.0 Grade 1: Mild; asymptomatic or mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2:Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant, but not immediately life-threatening: hospitalization or prolongation of hospitalization indicated; disabling or limiting self-care ADL; Grade 4: Life-threatening consequences or urgent intervention indicated; Grade 5: Death related to AE. Multiple occurrences of AEs in the same category at the worst (highest) NCIC-CTCAE grade for an individual are counted only once.
Safety-evaluable population included all randomized participants in Cohort 1 who received any amount of study treatment. All AEs were reported until 30 days after final dose or until initiation of new systemic anti-cancer therapy (whichever occurs first). Serious AEs and AEs of special interest (AESIs) and treatment-related non-serious AEs that lead to surgery delay were reported until 135 days after final dose or until initiation of new systemic anti-cancer therapy (whichever occurs first).
Posted
Count of Participants
Participants
From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (Up to 5.6 months)
ID
Title
Description
OG000
Secondary
Number of Participants With Immune-related AEs Grade ≥ 3 for Cohort 1
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. Participants with immune-related adverse events Grade ≥ 3 were reported.
Safety-evaluable population included all randomized participants in Cohort 1 who received any amount of the study treatment.
Posted
Count of Participants
Participants
From initiation of study treatment up to 135 days after the final dose of study treatment (Up to 5.6 months)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Secondary
Rate of Delayed Surgery Due to Treatment-related AEs
Rate of delayed surgery due to treatment related AEs was defined as the percentage of participants for whom surgery was delayed due to treatment-related AEs for more than 2 weeks. An AE was any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of the investigational product, whether considered related to the investigational product.
Safety-evaluable population included all randomized participants in Cohort 1 who received any amount of the study treatment.
Posted
Number
percentage of participants
Time of surgery (scheduled at Week 7) up to 40.1 weeks
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Secondary
Duration of Surgery Delay Due to Treatment-related AEs
Duration of surgery delay due to treatment related AEs was calculated on the participants for whom surgery was delayed due to treatment-related AEs for more than 2 weeks. An AE was any untoward medical occurrence in a clinical investigation participants administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of the investigational product, whether considered related to the investigational product.
Safety-evaluable population included all randomized participants in Cohort 1 who received any amount of the study treatment. Participants with a surgery delay of more than 2 weeks due to treatment-related AE were analyzed.
Posted
Mean
Standard Deviation
weeks
Time of surgery (scheduled at Week 7) up to 40.1 weeks
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Secondary
Surgical Complication Rates for Cohort 1
Surgical complications were scored according to the Clavien-Dindo surgical classification. Complication rates for every grade were reported and scored for participants who underwent CLND. The Surgical complications according to Clavien-Dindo can be classified into the following grades: Grade I: Any complication that does not need pharmacological treatment or surgical, endoscopic, and radiological interventions. Grade II: Complications that require pharmacological treatment with drugs or blood transfusions and total parenteral nutrition. Grade III: Complications that require surgical, endoscopic, or radiological intervention with (Grade IIIb) or without (Grade IIIa) general anesthesia. Grade IV: Life-threatening complications requiring intensive care unit (ICU) management, which may be single organ (Grade IVa) or multiorgan (Grade IVb) dysfunction. Grade V: Complications that might cause the death of a participant. Values have been rounded off to 2 decimal digits.
Safety-evaluable population included all randomized participants in Cohort 1 who received any amount of the study treatment. Overall number analyzed is the number of participants who underwent surgery. Number analyzed is the number of participants with surgical complication.
Posted
Number
percentage of participants
At treatment discontinuation visit (Week 13) and Surgery Follow-Up (6 months after surgery)
ID
Title
Description
OG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Secondary
Progression-Free Survival (PFS) for Cohort 2
PFS after randomization/enrollment was defined as the time from randomization/enrollment to the first occurrence of disease progression or death from any cause (whichever occurred first), as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on the study (including baseline) and/or unequivocal progression of a non-target lesion and/or any new lesion. Participants without documented disease progression or death at the time of analysis were censored at the day of the last tumor assessment. Kaplan-Meier method was used to estimate the median for PFS, with 95% CIs constructed by using the Brookmeyer and Crowley method.
Efficacy-evaluable population included all participants in Cohort 2 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Median
95% Confidence Interval
months
From randomization/enrollment to first documented disease progression or death or last tumor assessment (up to 3.6 months)
ID
Title
Description
OG000
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Secondary
OS for Cohort 2
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. Kaplan-Meier method was used to estimate the median for OS, with 95% CIs constructed by using the Brookmeyer and Crowley method.
Efficacy-evaluable population included all participants in Cohort 2 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Median
95% Confidence Interval
months
From randomization/enrollment to death from any cause or last known to be alive (Up to 24.2 months)
ID
Title
Description
OG000
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Units
Counts
Participants
OG000
Secondary
OS Rates at Specific Timepoints for Cohort 2
OS was defined as the time from randomization to death from any cause. OS rate is percentage of participants who were event free for OS. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. OS rate at specific time points were estimated using the Kaplan-Meier method, with 95% CIs calculated based on Greenwood's estimate for the variance.
Efficacy-evaluable population included all participants in Cohort 2 who received at least one dose of each drug for their assigned treatment regimen. Number analyzed per timepoint are unique number of participants out of all the assessed participants who remain at risk for an OS event at that timepoint. Different participants may have contributed data for each timepoint.
Posted
Number
95% Confidence Interval
percentage of participants
Months 3, 6 and 12
ID
Title
Description
OG000
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Units
Counts
Participants
Secondary
Duration of Response (DOR) for Cohort 2
DOR was defined as the time from the first occurrence of a documented objective response (OR) to disease progression or death from any cause (whichever occurred first), as determined by the investigator according to RECIST v1.1. OR was defined as a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR = at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on the study (including baseline). Participants without PD or death at time of analysis were censored at time of last tumor assessment. Kaplan-Meier method was used to estimate median for DOR, with 95% CIs constructed using Brookmeyer & Crowley method.
Efficacy-evaluable population included all participants in Cohort 2 who received at least one dose of each drug for their assigned treatment regimen.
DOR was only evaluated in participants who achieved an OR (CR or PR).
Posted
Time from the first occurrence of a documented OR to disease progression or death from any cause (up to 3.6 months)
ID
Title
Description
OG000
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Secondary
Disease Control Rate (DCR) for Cohort 2
DCR was defined as the percentage of participants with stable disease for ≥ 12 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Stable disease was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on the study (including baseline). DCR was calculated for each treatment arm, with 95% CIs estimated through use of Clopper-Pearson's exact method.
Efficacy-evaluable population included all participants in Cohort 2 who received at least one dose of each drug for their assigned treatment regimen.
Posted
Number
95% Confidence Interval
percentage of participants
From randomization up to 3.6 months
ID
Title
Description
OG000
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
Units
Secondary
Number of Participants With AEs and Severity of AEs Determined According to NCI CTCAE v5.0 for Cohort 2
An AE=any untoward medical occurrence in clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. AE can therefore be any unfavorable & unintended sign, symptom/disease temporally associated with using an investigational product, whether or not considered related to the investigational product. Severity was determined per NCI CTCAE v5.0 Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care ADL; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE. Multiple occurrences of AEs in 1 individual are counted once at highest grade.
Safety-evaluable population included all randomized participants in Cohort 2 who received any amount of the study treatment. All AEs were reported until 30 days after the final dose or until initiation of new systemic anti-cancer therapy (whichever occurs first). Serious AEs and AESIs were reported until 135 days after the final dose or until initiation of new systemic anti-cancer therapy (whichever occurs first).
Posted
Count of Participants
Participants
From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (Up to 10 months)
ID
Title
Description
OG000
Cohort 2: Tobemstomig + Tiragolumab
Time Frame
From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (Up to 5.6 months for Cohort 1 and 10 months for Cohort 2); All-cause Mortality: Randomization up to the end of long-term follow-up (Up to approximately 25 months for Cohort 1 and 24.2 months for Cohort 2)
Description
Safety evaluable population included all randomized participants who received at least one dose of the study drug.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
1
22
4
22
18
22
EG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
1
40
9
40
34
40
EG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
2
20
3
20
18
20
EG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
1
20
6
20
18
20
EG004
Cohort 2: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
5
8
1
8
7
8
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Myocardial ischaemia
Cardiac disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG0030 events0 affected20 at risk
EG0040 events0 affected8 at risk
Myocarditis
Cardiac disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Ventricular fibrillation
Cardiac disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Enteritis
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Immune-mediated hepatitis
Hepatobiliary disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Catheter site infection
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Cellulitis
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Infected seroma
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Meningitis aseptic
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Pneumonia
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Postoperative wound infection
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Post procedural haematoma
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Wound dehiscence
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Heart rate irregular
Investigations
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Troponin increased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Hyperlipasaemia
Metabolism and nutrition disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Myositis
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Immune-mediated lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Scar excision
Surgical and medical procedures
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Haematoma
Vascular disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Hypotension
Vascular disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Lymphatic fistula
Vascular disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG0030 events0 affected20 at risk
EG0043 events2 affected8 at risk
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA version 27.0
Systematic Assessment
EG0004 events4 affected22 at risk
EG0017 events7 affected40 at risk
EG0023 events3 affected20 at risk
EG003
Hypophysitis
Endocrine disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0013 events3 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Thyroiditis
Endocrine disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Dry eye
Eye disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Eyelid ptosis
Eye disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Retinal detachment
Eye disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events1 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Abdominal tenderness
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0013 events3 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0013 events3 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0013 events3 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Gastrointestinal pain
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0004 events4 affected22 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Asthenia
General disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0012 events2 affected40 at risk
EG0024 events4 affected20 at risk
EG003
Chest pain
General disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Chills
General disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Extravasation
General disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Fatigue
General disorders
MedDRA version 27.0
Systematic Assessment
EG0007 events7 affected22 at risk
EG00115 events15 affected40 at risk
EG0024 events3 affected20 at risk
EG003
Hyperthermia
General disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Influenza like illness
General disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Oedema peripheral
General disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0012 events2 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Pain
General disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Peripheral swelling
General disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Pyrexia
General disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0022 events2 affected20 at risk
EG003
Xerosis
General disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0012 events2 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Hypertransaminasaemia
Hepatobiliary disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Contrast media allergy
Immune system disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
COVID-19
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Cystitis
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Device related infection
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0018 events6 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Joint injury
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Post procedural constipation
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Procedural nausea
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0012 events2 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0018 events8 affected40 at risk
EG0024 events4 affected20 at risk
EG003
Seroma
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0003 events3 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Amylase increased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0013 events3 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Blood creatinine increased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
International normalised ratio decreased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Lipase increased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0014 events3 affected40 at risk
EG0020 events0 affected20 at risk
EG003
SARS-CoV-2 test positive
Investigations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Serum ferritin decreased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Troponin increased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Weight decreased
Investigations
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0012 events2 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Hyperamylasaemia
Metabolism and nutrition disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0003 events3 affected22 at risk
EG0013 events2 affected40 at risk
EG0022 events2 affected20 at risk
EG003
Groin pain
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Joint stiffness
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0011 events1 affected40 at risk
EG0022 events2 affected20 at risk
EG003
Myositis
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0012 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Dizziness
Nervous system disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Headache
Nervous system disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Lethargy
Nervous system disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Sensory disturbance
Nervous system disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0011 events1 affected40 at risk
EG0022 events2 affected20 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Renal impairment
Renal and urinary disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0012 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA version 27.0
Systematic Assessment
EG0002 events2 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0011 events1 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Lichenoid keratosis
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0003 events2 affected22 at risk
EG0014 events2 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0008 events8 affected22 at risk
EG0016 events6 affected40 at risk
EG0022 events2 affected20 at risk
EG003
Psoriasis
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0007 events6 affected22 at risk
EG0018 events7 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Rash erythematous
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0021 events1 affected20 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0013 events3 affected40 at risk
EG0022 events2 affected20 at risk
EG003
Haematoma
Vascular disorders
MedDRA version 27.0
Systematic Assessment
EG0000 events0 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Lymphoedema
Vascular disorders
MedDRA version 27.0
Systematic Assessment
EG0001 events1 affected22 at risk
EG0010 events0 affected40 at risk
EG0020 events0 affected20 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG00320
Title
Denominators
Categories
Title
Measurements
OG00081.8(59.72 to 94.81)
OG00175.0(58.80 to 87.31)
OG00250.0(27.20 to 72.80)
OG00360.0(36.05 to 80.88)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference in pRR
-6.82
2-Sided
95
-31.31
17.68
Superiority
OG000
OG002
Difference in pRR
-31.82
2-Sided
95
-63.79
0.16
Superiority
OG000
OG003
Difference in pRR
-21.82
2-Sided
95
-53.44
9.80
Superiority
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG00320
Title
Denominators
Categories
Title
Measurements
OG00019.55(19.55 to NA)The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
OG001NA(14.09 to NA)The median and upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
OG00222.51(6.08 to NA)The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
OG003NA(6.51 to NA)The median and upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
2.09
2-Sided
95
0.42
10.42
Superiority
OG000
OG002
Hazard Ratio (HR)
3.95
2-Sided
95
0.79
19.70
Superiority
OG000
OG003
Hazard Ratio (HR)
6.27
2-Sided
95
0.73
53.70
Superiority
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00138
OG00218
OG00319
Title
Denominators
Categories
Title
Measurements
OG00017.91(17.91 to NA)The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
OG00117.08(11.79 to NA)The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
OG00220.90(4.40 to NA)The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
OG003NA(NA to NA)The median and 95% CI was not estimable due to insufficient number of participants with events.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
1.41
2-Sided
95
0.25
7.75
Superiority
OG000
OG002
Hazard Ratio (HR)
2.09
2-Sided
95
0.35
12.62
Superiority
OG000
OG003
Hazard Ratio (HR)
2.39
2-Sided
95
0.22
26.32
Superiority
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG00320
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)The median and 95% CI was not estimable due to insufficient number of participants with events.
OG001NA(NA to NA)The median and 95% CI was not estimable due to insufficient number of participants with events.
OG002NA(NA to NA)The median and 95% CI was not estimable due to insufficient number of participants with events.
OG003NA(NA to NA)The median and 95% CI was not estimable due to insufficient number of participants with events.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
0.78
2-Sided
95
0.05
12.39
Superiority
OG000
OG002
Hazard Ratio (HR)
2.59
2-Sided
95
0.23
28.65
Superiority
OG000
OG003
Hazard Ratio (HR)
1.16
2-Sided
95
0.07
18.58
Superiority
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG00320
Title
Denominators
Categories
Title
Measurements
OG00059.1(36.35 to 79.29)
OG00137.5(22.73 to 54.20)
OG00235.0(15.39 to 59.22)
OG00360.0(36.05 to 80.88)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Difference in ORR
-21.59
2-Sided
95
-50.55
7.37
Superiority
OG002
Difference in ORR
-24.09
2-Sided
95
-58.17
9.99
Superiority
OG000
OG003
Difference in ORR
0.91
2-Sided
95
-33.58
35.40
Superiority
Cohort 1: Nivolumab + Ipilimumab (Control)
Participants received nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG00320
Title
Denominators
Categories
AE, Any Grade
Title
Measurements
OG00019
OG00136
OG00219
OG00318
Worst Grade, Grade 1 AE
Title
Measurements
OG0004
OG00113
OG0029
OG003
Worst Grade, Grade 2 AE
Title
Measurements
OG0009
OG00115
OG0029
OG003
Worst Grade, Grade 3 AE
Title
Measurements
OG0004
OG0015
OG0021
OG003
Worst Grade, Grade 4 AE
Title
Measurements
OG0002
OG0013
OG0020
OG003
Worst Grade, Grade 5 AE
Title
Measurements
OG0000
OG0010
OG0020
OG003
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG00320
Title
Denominators
Categories
Title
Measurements
OG0005
OG0011
OG0020
OG0033
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00140
OG00220
OG00320
Title
Denominators
Categories
Title
Measurements
OG00013.6
OG0012.5
OG0020
OG0035.0
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG0003
OG0011
OG0020
OG0031
Title
Denominators
Categories
Title
Measurements
OG00017.0± 14.8
OG0015.1± NAThe Standard Deviation (SD) was not estimable due to insufficient number of participants with events.
OG0033.0± NAThe SD was not estimable due to insufficient number of participants with events.
OG001
Cohort 1: Tobemstomig 2100 mg
Participants received a fixed dose of tobemstomig 2100 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG002
Cohort 1: Atezolizumab + Tiragolumab
Participants received atezolizumab 1200 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
OG003
Cohort 1: Tobemstomig + Tiragolumab
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. Post-surgery at the discretion of the investigator, participants started either adjuvant therapy or an observation phase from Week 13.
Units
Counts
Participants
OG00022
OG00138
OG00218
OG00319
Title
Denominators
Categories
Treatment Discontinuation Visit: Grade 0
ParticipantsOG00022
ParticipantsOG00138
ParticipantsOG00218
ParticipantsOG00319
Title
Measurements
OG0000
OG0010
OG0025.55
OG003
Treatment Discontinuation Visit: Grade I
ParticipantsOG00022
ParticipantsOG00138
ParticipantsOG00218
ParticipantsOG00319
Treatment Discontinuation Visit: Grade II
ParticipantsOG00022
ParticipantsOG00138
ParticipantsOG00218
ParticipantsOG00319
Treatment Discontinuation Visit: Grade IIIa
ParticipantsOG00022
ParticipantsOG00138
ParticipantsOG00218
ParticipantsOG00319
Treatment Discontinuation Visit: Grade IIIb
ParticipantsOG00022
ParticipantsOG00138
ParticipantsOG00218
ParticipantsOG00319
Treatment Discontinuation Visit: Grade IVa
ParticipantsOG00022
ParticipantsOG00138
ParticipantsOG00218
ParticipantsOG00319
Long-term Follow-up Month 6: Grade 0
ParticipantsOG00022
ParticipantsOG00137
ParticipantsOG00217
ParticipantsOG00317
Long-term Follow-up Month 6: Grade I
ParticipantsOG00022
ParticipantsOG00137
ParticipantsOG00217
ParticipantsOG00317
Long-term Follow-up Month 6: Grade II
ParticipantsOG00022
ParticipantsOG00137
ParticipantsOG00217
ParticipantsOG00317
Long-term Follow-up Month 6: Grade IIIa
ParticipantsOG00022
ParticipantsOG00137
ParticipantsOG00217
ParticipantsOG00317
Long-term Follow-up Month 6: Grade IIIb
ParticipantsOG00022
ParticipantsOG00137
ParticipantsOG00217
ParticipantsOG00317
Long-term Follow-up Month 6: Grade IVa
ParticipantsOG00022
ParticipantsOG00137
ParticipantsOG00217
ParticipantsOG00317
Units
Counts
Participants
OG0008
Title
Denominators
Categories
Title
Measurements
OG0002.07(1.68 to 2.37)
8
Title
Denominators
Categories
Title
Measurements
OG0008.94(4.17 to NA)The upper limit of the 95% CI was not estimable due to insufficient number of participants with events.
OG0008
Title
Denominators
Categories
3 months
ParticipantsOG0007
Title
Measurements
OG000100.0(100.0 to 100.0)
6 months
ParticipantsOG0004
Title
Measurements
OG00071.43(37.96 to 100.0)
12 months
ParticipantsOG0002
Title
Measurements
OG00047.62(3.47 to 91.77)
Units
Counts
Participants
OG0000
Counts
Participants
OG0008
Title
Denominators
Categories
Title
Measurements
OG0000(0.00 to 36.94)
Participants received tobemstomig 2100 mg IV and tiragolumab 600 mg IV on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.