Study of Tremelimumab in Patients With Advanced Solid Tumors

Objective response rate (ORR) during the initial tremelimumab monotherapy phase was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.

Time frame: From baseline to 12 months in the tremelimumab monotherapy phase

Population: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

BoR during the initial tremelimumab monotherapy phase was calculated based on the overall visit responses from each RECIST 1.1 assessment and was defined as the best response a patient had during their time in the study (from CR, PR, SD, PD or not evaluable \[NE\]) obtained among all tumor assessment visits from baseline until end of treatment or determination of PD. The BoR was summarized by percentage of patients for each category (CR, PR, SD, PD, and NE).

Time frame: From baseline to 12 months in the tremelimumab monotherapy phase

Population: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

BoR during the retreatment phase was calculated based on the overall visit responses from each RECIST 1.1 assessment and was defined as the best response a patient had during their time in the study (from CR, PR, SD, PD or NE) obtained among all tumor assessment visits from baseline until end of treatment or determination of PD. The BoR was summarized by percentage of patients for each category (CR, PR, SD, PD, and NE).

Time frame: From baseline to 12 months in retreatment phase

Population: Analysis was performed on the MEDI and COMBO analysis sets (all patients who were treated with tremelimumab, received at least 1 dose of durvalumab monotherapy or durvalumab + tremelimumab combination therapy as applicable, and who had a baseline tumor assessment prior to dosing).

DCR during the retreatment phase was defined as the percentage of patients who had a BoR of CR or PR in the first 3 months (PDAC patients) or 4 months (UBC and TNBC patients) or who had demonstrated SD for a minimum interval of 3 or 4 months following the start of study treatment. DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. 95% CIs were calculated using the Clopper Pearson method.

Time frame: From baseline to 4 months in retreatment phase

Population: Analysis was performed on the MEDI and COMBO analysis sets (all patients who were treated with tremelimumab, received at least 1 dose of durvalumab monotherapy or durvalumab + tremelimumab combination therapy as applicable, and who had a baseline tumor assessment prior to dosing).

DCR during the initial tremelimumab monotherapy phase was defined as the percentage of patients who had a best objective response (BoR) of CR or PR in the first 3 months (PDAC patients) or 4 months (UBC and TNBC patients) and 12 months (all patients), or who had demonstrated stable disease (SD) for a minimum interval of 3, 4 or 12 months following the start of study treatment. DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. 95% CIs were calculated using the Clopper Pearson method.

Time frame: From baseline to 12 months in the tremelimumab monotherapy phase

Population: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

DoR during the retreatment phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The time of the initial response was defined as the latest of the dates contributing toward the first visit response of CR or PR. If a patient did not progress following a response, then their DoR was censored at the PFS censoring time. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.

Time frame: From baseline to 12 months in retreatment phase

Population: Analysis was performed on the MEDI and COMBO analysis sets (all patients who were treated with tremelimumab, received at least 1 dose of durvalumab monotherapy or durvalumab + tremelimumab combination therapy as applicable, and who had a baseline tumor assessment prior to dosing).

DoR during the initial tremelimumab monotherapy phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The time of the initial response was defined as the latest of the dates contributing toward the first visit response of CR or PR. If a patient did not progress following a response, then their DoR was censored at the progression-free survival (PFS) censoring time. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.

Time frame: From baseline to 12 months in the tremelimumab monotherapy phase

Population: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

OS during the retreatment phase was defined as the time from the date of first dose until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

Time frame: From baseline in retreatment phase to final data cut-off date

Population: Analysis was performed on the MEDI and COMBO analysis sets (all patients who were treated with tremelimumab, received at least 1 dose of durvalumab monotherapy or durvalumab + tremelimumab combination therapy as applicable, and who had a baseline tumor assessment prior to dosing).

OS was defined as the time from the date of first dose until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. OS is presented from start of tremelimumab monotherapy phase and includes the retreatment phase if the patient entered the corresponding treatment phase. Median OS was calculated using the Kaplan-Meier technique.

Time frame: From baseline to final data cut-off date

Population: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

PFS during the retreatment phase was assessed by the site Investigator using RECIST 1.1 and defined as the time from the date of enrollment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from therapy or received another anticancer therapy prior to progression. Progression events that did not occur within 3 months (PDAC patients) or 4 months (UBC/TNBC patients) of the last evaluable assessment (or first dose) were censored. Median PFS was calculated using the Kaplan-Meier technique.

Time frame: From baseline to 12 months in retreatment phase

Population: Analysis was performed on the MEDI and COMBO analysis sets (all patients who were treated with tremelimumab, received at least 1 dose of durvalumab monotherapy or durvalumab + tremelimumab combination therapy as applicable, and who had a baseline tumor assessment prior to dosing).

PFS during the initial tremelimumab monotherapy phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of enrollment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from therapy or received another anticancer therapy prior to progression. Progression events that did not occur within 3 months (PDAC patients) or 4 months (UBC/TNBC patients) of the last evaluable assessment (or first dose) were censored. Median PFS was calculated using the Kaplan-Meier technique.

Time frame: From baseline to 12 months in the tremelimumab monotherapy phase

Population: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

ORR was assessed by the site Investigator using RECIST 1.1 and was defined as the percentage of patients with a confirmed overall response of CR or PR and was based on all treated patients who had measurable disease at baseline (Day 1) and who sequenced to durvalumab monotherapy (MEDI treatment phase) or durvalumab + tremelimumab combination therapy (COMBO treatment phase). 95% CIs were calculated using the Clopper Pearson method.

Time frame: From baseline to 12 months in retreatment phase

Population: Analysis was performed on the MEDI and COMBO analysis sets (all patients who were treated with tremelimumab, received at least 1 dose of durvalumab monotherapy or durvalumab + tremelimumab combination therapy as applicable, and who had a baseline tumor assessment prior to dosing).