A Study Evaluating Efficacy and Safety of Multiple Treatment Combinations in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (Morpheus-Head and Neck Cancer)

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.

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.

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.

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.

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.

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.

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.

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 .

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 .

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.

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.

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.

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.

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.