Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer

The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and hazard ratio (HR) and confidence intervals (CIs) from a stratified Cox proportional hazards model. Analyses were stratified on World Health Organization/ Eastern Cooperative Oncology Group performance status (WHO/ECOG PS) (0 or 1) and number of prior lines of therapy in recurrent or metastatic (R/M) setting (1 or 2).

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either oropharyngeal cancer (OPC) HPV negative or non OPC regardless of the HPV status.

The DoR is defined as the time from the date of first documented confirmed response until date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the SoDs of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest previous SoDs (nadir) and the sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. The DoR was analyzed using Kaplan-Meier technique.

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either OPC HPV negative or non OPC regardless of the HPV status. The DoR is assessed for only those participants who had OR.

The DoR is defined as the time from the date of first documented confirmed response until date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the SoDs of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest previous SoDs (nadir) and the sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. The DoR was analyzed using Kaplan-Meier technique.

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The FAS included all participants randomized at least 2 months before the DCO 11May2022 (i.e. on or before 11Mar2022). The DoR is assessed for only those participants who had OR.

Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology and clinical chemistry. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Time frame: Day 1 through 21.4 months (maximum observed duration)

Population: The Safety Analysis Set included all participants randomized at least 2 months before the DCO 01Sep2022 (i.e. on or before 01Jul2022).

Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) reported as TEAEs are reported. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Time frame: Day 1 through 21.4 months (maximum observed duration)

Population: The Safety Analysis Set included all participants randomized at least 2 months before the DCO 01Sep2022 (i.e. on or before 01Jul2022).

Participants with Abnormal ECGs reported as TEAEs are reported. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Time frame: Day 1 through 21.4 months (maximum observed duration)

Population: The Safety Analysis Set (SAS) included all participants randomized at least 2 months before the DCO 01Sep2022 (i.e. on or before 01Jul2022).

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Time frame: Day 1 through 21.4 months (maximum observed duration)

Population: The Safety Analysis Set included all participants randomized at least 2 months before the DCO 01Sep2022 (i.e. on or before 01Jul2022).

The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on HPV status (OPC HPV positive or HPV-unrelated), WHO/ECOG PS (0 or 1) and number of prior lines of therapy in R/M setting (1 or 2).

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The FAS included all participants randomized at least 2 months before the DCO 11May2022 (i.e. on or before 11Mar2022).

The OR is defined as the percentage of participants with at least one confirmed investigator-assessed response of complete response (CR) or partial response (PR) as assessed by RECIST 1.1 guidelines. The CR is defined as disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis \< 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either OPC HPV negative or non OPC regardless of the HPV status. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

The OR is defined as the percentage of participants with at least one confirmed investigator-assessed response of CR or PR as assessed by RECIST 1.1 guidelines. The CR is defined as disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis \< 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The FAS included all participants randomized at least 2 months before the DCO 11May2022 (i.e. on or before 11Mar2022). Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

PFS per RECIST 1.1 as assessed by the investigator is defined as time from randomization until date of RECIST 1.1-defined radiological progressive disease (PD) or death regardless of whether participant withdraws from therapy or received subsequent anticancer therapy prior to progression. PD: at least 20% increase in sum of diameters of target lesions (TLs), taking as reference the smallest sum on study (nadir) and sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. PFS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on HPV status, WHO/ECOG PS (0/1) and no. of prior lines of therapy in R/M setting.

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The FAS included all participants randomized at least 2 months before the DCO 11May2022 (i.e. on or before 11Mar2022).

PFS per RECIST 1.1 as assessed by the investigator is defined as time from randomization until date of RECIST 1.1-defined radiological progressive disease (PD) or death regardless of whether participant withdraws from therapy or received subsequent anticancer therapy prior to progression. PD: at least 20% increase in sum of diameters of target lesions (TLs), taking as reference the smallest sum on study (nadir) and sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing non-TLs (NTLs) or appearance of new lesions. PFS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on WHO/ECOG PS (0/1) and no. of prior lines of therapy in R/M setting.

Time frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Population: The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either OPC HPV negative or non OPC regardless of the HPV status.