A Study Evaluating Efficacy and Safety of Multiple Treatm... | NCT05459129

Label	Type	Description	Intervention Names
Atezo + Tira	Active Comparator	Participants in the atezolizumab plus tiragolumab arm will receive treatment for two cycles (6 weeks) until surgery or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	Drug: Atezolizumab Drug: Tiragolumab
Atezo + Tira + CP	Experimental	Participants in the atezolizumab plus tiragolumab plus carboplatin plus paclitaxel arm arm will receive treatment for two cycles (6 weeks) until surgery or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	Drug: Atezolizumab Drug: Tiragolumab Drug: Carboplatin Drug: Paclitaxel

Name	Type	Description	Arm Group Labels	Other Names
Atezolizumab	Drug	Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.	Atezo + Tira Atezo + Tira + CP

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Pathologic Complete Response (pCR) as Determined by Local Pathologic Review	pCR was defined as the absence of any viable primary tumor at time of surgical resection, as determined by local pathologic review. The pCR rate was defined as the percentage of participants who achieved a pCR. pCR rate was calculated for each arm, along with the 95% confidence interval (CI) estimated using the Clopper-Pearson method and the 95% CI for difference in rates was estimated using the Wald method with continuity correction. Participants with missing or no pathologic response assessment were classified as non-responders. Percentages have been rounded off to the nearest whole number.	At the time of surgery (Week 7 ± 1 week)

Secondary Outcomes

Measure	Description	Time Frame
Pathologic Response Rate (pRR) as Determined by Local Pathologic Review	pRR was defined as the percentage of participants with a pCR, major pathological response (mPR), and pathological partial response (pPR). pCR was defined as the absence of any viable primary tumor at time of surgical resection, as determined by local pathologic review. mPR was defined as ≤10% residual viable tumor at the time of surgical resection in the primary tumor. pPR was defined as ≤ 50% residual viable tumor at the time of surgical resection in the primary tumor. pRR was calculated for each arm, along with the 95% CI, estimated using the Clopper-Pearson method, and the 95% CI for the difference in rates was estimated using the Wald method with continuity correction. Percentages have been rounded off to the nearest whole number.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Eastern Cooperative Oncology Group Performance Status of 0 or 1
Histologically confirmed, resectable Stage III-IVA SCCHN
Eligible candidate for R0 resection with curative intent at the time of screening
HPV-negative test for oropharyngeal carcinoma, as determined locally by p16 immunohistochemistry (IHC), in situ hybridization, or polymerase chain reaction-based assay
Measurable disease (at least one target lesion), as assessed according to RECIST v1.1
PD-L1 expression, defined as a combined positive score (CPS) >= 1
Adequate hematologic and end-organ function
Negative HIV test with the following exception: 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.
Negative hepatitis B surface antigen (HBsAg) test at screening
Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb), Positive total hepatitis B core antibody (HBcAb) followed by a negative quantitative hepatitis B virus (HBV) DNA.

Exclusion Criteria:

HPV-positive oropharyngeal cancer, as determined locally by p16 IHC, in situ hybridization, or by polymerase chain reactions-based assay
Distantly metastasized SCCHN
Any prior therapy for SCCHN, including immunotherapy, chemotherapy, or RT
Prior treatment with any of the protocol-specified study treatments
Treatment with investigational therapy within 42 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
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT scan)
History of malignancy other than SCCHN within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5 -year OS rate>90%)
Active tuberculosis
Severe infection within 4 weeks prior to initiation of study treatment
Treatment with therapeutic or prophylactic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment
Significant cardiovascular disease such a New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhytmia, or unstable angina
Major surgical procedure, other than for diagnosis, within 4 weeks prior to study initiation of study treatment, or anticipation of need for a major surgical procedure other than tumor resection, during the study
Any of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of investigational drug, may affect the interpretation of the results, impair the ability of the patient to participate in the study, or renders the patient at high risk form treatment complications
History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
Known allergy or hypersensitivity to any of the study drugs or their excipients
Known intolerance to any of the drugs required for premedication
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Eligible only for the control arm
Active EBV infection or known or suspected chronic EBV infection at screening

Specific Exclusion Criteria for Atezo+Tira+CP:

Known severe allergy or hypersensitivity to placlitaxel, platinum or platinum-containing compounds
Known history of severe hypersensitivity to products containing Cremophor EL
Creatinine clearance <45m./min (Calculated using the Cockcroft-Gault formula)

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope		Duarte	California	91010	United States
Thomas Jefferson University Hospital

ID	Title	Description
FG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 milligrams (mg) as intravenous (IV) infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
FG001

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	Jan 29, 2024

ID	Title	Description
BG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
BG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG00212

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

Percentage of Participants With Pathologic Complete Response (pCR) as Determined by Local Pathologic Review

pCR was defined as the absence of any viable primary tumor at time of surgical resection, as determined by local pathologic review. The pCR rate was defined as the percentage of participants who achieved a pCR. pCR rate was calculated for each arm, along with the 95% confidence interval (CI) estimated using the Clopper-Pearson method and the 95% CI for difference in rates was estimated using the Wald method with continuity correction. Participants with missing or no pathologic response assessment were classified as non-responders. Percentages have been rounded off to the nearest whole number.

Efficacy-evaluable population included all participants who received at least one dose of each drug for their assigned treatment regimen.

Posted

Number

95% Confidence Interval

percentage of participants

At the time of surgery (Week 7 ± 1 week)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Units	Counts
Participants	OG0006 OG0016

Title

Denominators

Categories

Title	Measurements
	OG00016.7(0.42 to 64.12) OG00150.0(11.81 to 88.19)

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 pCR Rates	33.33			2-Sided	95	-33.23	99.90					Superiority

Secondary

Pathologic Response Rate (pRR) as Determined by Local Pathologic Review

pRR was defined as the percentage of participants with a pCR, major pathological response (mPR), and pathological partial response (pPR). pCR was defined as the absence of any viable primary tumor at time of surgical resection, as determined by local pathologic review. mPR was defined as ≤10% residual viable tumor at the time of surgical resection in the primary tumor. pPR was defined as ≤ 50% residual viable tumor at the time of surgical resection in the primary tumor. pRR was calculated for each arm, along with the 95% CI, estimated using the Clopper-Pearson method, and the 95% CI for the difference in rates was estimated using the Wald method with continuity correction. Percentages have been rounded off to the nearest whole number.

Efficacy-evaluable population included all participants who received at least one dose of each drug for their assigned treatment regimen.

Posted

Number

95% Confidence Interval

percentage of participants

At the time of surgery (Week 7 ± 1 week)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Event-Free Survival (EFS)

EFS was defined as the time from randomization to disease progression (PD) that precludes surgery, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); local, regional, or distant disease recurrence or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), and must also demonstrate an absolute increase of ≥ 5 millimeters (mm). Kaplan-Meier method was used to estimate the median for EFS, and 95% Cls was constructed using Brookmeyer and Crowley method. Data from participants who have not experienced such events were censored at the time of the last tumor assessment. Due to the early termination of the study, the limited sample size and follow-up time no meaningful conclusions can be made in terms of median EFS per arm or HR between the arms.

Efficacy-evaluable population included all participants who received at least one dose of each drug for their assigned treatment regimen.

Posted

Median

95% Confidence Interval

months

From randomization to PD disease recurrence or death (Up to 9.2 months)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001

Secondary

Relapse-Free Survival (RFS)

RFS was defined as the time from surgery to the first documented recurrence of disease or death from any cause. Recurrent disease included local, regional, or distant recurrence: local recurrence was defined as tumor regrowth within 2 centimeter (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 who did not have documented recurrence of disease or died, RFS was censored at the day of the last tumor assessment. Kaplan-Meier method was used to estimate the median for RFS, and 95% Cls was constructed using Brookmeyer and Crowley method. Due to the early termination of the study, the limited sample size and follow-up time no meaningful conclusions can be made in terms of median RFS per arm or HR between the arms.

Adjuvant-evaluable population included all participants who received at least one dose of each drug and who completed surgery.

Posted

Median

95% Confidence Interval

months

From surgery (scheduled at Week 7 ± 1 week) to first documented disease recurrence or death (up to 7.6 months)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001

Secondary

Overall Survival (OS)

OS was defined as the time from randomization to death from any cause. Data from 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, and 95% Cls was constructed using Brookmeyer and Crowley method. Due to the early termination of the study, the limited sample size and follow-up time no meaningful conclusions can be made in terms of median OS and no further OS analysis are reported.

Efficacy-evaluable population included all 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 9.2 months)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Objective Response Rate (ORR)

ORR was defined as the percentage of participants with an objective tumor response of complete response (CR) or partial response (PR) as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) have a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. ORR was calculated for each arm, along with 95% CIs, using the Clopper-Pearson method and the 95% CI for difference in rates was estimated using the Wald method with continuity correction. Participants with missing or no response assessments were classified as non-responders.

Efficacy-evaluable population included all participants 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	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Landmark EFS Rate

EFS was defined as the time from randomization to PD that precludes surgery, as determined by the investigator according to RECIST v1.1; local, regional, or distant disease recurrence or death from any cause, whichever occurs first. EFS rate was defined as the percentage of participants who are event-free at the specified timepoints. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), and must also demonstrate an absolute increase of ≥ 5 mm. Landmark EFS rates were estimated for each study arm using the Kaplan-Meier method, with 95% CIs calculated through the use of Greenwood's formula. Percentages have been rounded off to the nearest whole number. Due to the early termination of the study, the limited sample size and follow-up time no meaningful conclusions can be made.

Efficacy-evaluable population included all participants 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 EFS event at that timepoint. Different participants may have contributed data for each timepoint.

Posted

Number

95% Confidence Interval

percentage of participants

3 Months, 6 Months, and 1 Year

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Landmark RFS Rate

RFS was defined as the time from surgery to the first documented recurrence of disease or death from any cause. RFS rate was defined as the percentage of participants who are event-free at the specified timepoints. Recurrent disease included 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. Landmark RFS rates were estimated for each study arm using the Kaplan-Meier method, with 95% CIs calculated through the use of Greenwood's formula. Percentages have been rounded off to the nearest whole number. Due to the early termination of the study, the limited sample size and follow-up time no meaningful conclusions can be made .

Adjuvant-evaluable population included all participants who received at least one dose of each drug and who completed surgery. Number analyzed per timepoint are unique number of participants out of all the assessed participants who remain at risk for an RFS event at that timepoint. Different participants may have contributed data for each timepoint.

Posted

Number

95% Confidence Interval

percentage of participants

3 Months, 6 Months, and 1 Year

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Landmark OS Rate

OS was defined as the time from randomization to death from any cause. OS rate was defined as the percentage of participants who are event-free at the specified timepoints. Landmark OS rates were estimated for each study arm using the Kaplan-Meier method, with 95% CIs calculated through the use of Greenwood's formula. Due to the early termination of the study, the limited sample size and follow-up time no meaningful conclusions can be made .

Efficacy-evaluable population included all participants 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

3 Months, 6 Months, and 1 Year

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Number of Participants With Adverse Events (AEs)

Safety-evaluable population included all randomized participants who received any amount of dose of any component 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 5.1 months)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Number of Participants With Immune-Related AEs Grade >=3

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Grade 3 AEs were defined as severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living.

Safety-evaluable population included all randomized participants who received any amount of dose of any component of the study treatment.

Posted

Count of Participants

Participants

Up to 12 weeks

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

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 2 weeks. An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Safety-evaluable population included all randomized participants who received any amount of dose of any component of the study treatment. Percentages have been rounded off.

Posted

Count of Participants

Participants

Delay up to week after the planned time of surgery (scheduled at Week 7 ± 1 week) up to 2 weeks (up to Week 9)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Duration of Delayed Surgery 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 2 weeks. An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Safety-evaluable population included all randomized participants who received any amount of dose of any component of the study treatment. No participants had surgery delayed due to treatment-related AEs.

Posted

Delay up to week after the planned time of surgery (scheduled at Week 7 ± 1 week) up to 2 weeks (up to Week 9)

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.
OG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Secondary

Rate of Surgical Complications as Assessed According to the Clavien-Dindo Surgical Classification

Surgical complications were scored according to Clavien-Dindo surgical classification. Complication rates for every grade were reported & scored for participants who underwent complete lymph node dissection (CLND). The Surgical complications according to Clavien-Dindo can be classified into 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. Only categories with non-zero data was reported.

Safety-evaluable population included all randomized participants who received any amount of dose of any component of the study treatment. Overall number analyzed is the number of participants who underwent surgery. Percentages have been rounded off.

Posted

Number

percentage of participants

From Surgery (Week 7 ± 1 week) up to 5.1 months

ID	Title	Description
OG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Swelling of eyelid	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected6 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected6 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected6 at risk
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Mouth swelling	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected6 at risk EG0017 events4 affected6 at risk
Oral pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected6 at risk EG0013 events3 affected6 at risk
Tongue ulceration	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected6 at risk EG0014 events2 affected6 at risk
Influenza like illness	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Localised oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Mucosal inflammation	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected6 at risk
Appendicitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Candida infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Enterobacter infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Oral candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Otitis externa	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Peritumoural oedema	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected6 at risk
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Dysgeusia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Paraesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Anxiety	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Sleep disorder	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Dysuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected6 at risk
Hypotension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk

ID	Term
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006258	Head and Neck Neoplasms
D009371	Neoplasms by Site

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Atezolizumab + Tiragolumab	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	1	6	1	6	6	6
EG001	Atezolizumab + Tiragolumab + CP	Participants received atezolizumab, 1200 mg as IV infusion, along with tiragolumab, 600 mg, as IV infusion; carboplatin, at a dose of AUC 5 mg/mL/min as IV infusion and paclitaxel, 175 mg/m^2, as IV infusion on Day 1 of each 21-day cycle for 2 cycles (6 weeks) until surgery (Week 7 ± 1 week) or until unacceptable toxicity or loss of clinical benefit, whichever occurs first.	0	6	3	6	6	6

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Appendicitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Arterial injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected6 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk
Vascular rupture	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk

ID	Term
C000594389	atezolizumab
C000730814	Tiragolumab
D016190	Carboplatin
D017239	Paclitaxel