D4884C00001

AstraZeneca

City House,132 Hills Road, Cambridge, United Kingdom, CB2 1RY

Global Clinical Lead, AstraZeneca, +1 302 885 1180, ClinicalTrialTransparency@astrazeneca.com

Global Clinical Lead, AstraZeneca, +1 302 885 1180, ClinicalTrialTransparency@astrazeneca.com

No

No

No

Final

31 Dec 2018

Yes

17 Feb 2018

Yes

28 Mar 2023

No

To investigate the efficacy and safety of tremelimumab monotherapy, with subsequent treatment with either durvalumab monotherapy or durvalumab + tremelimumab combination therapy in patients with select advanced solid tumors.

This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics.

02 Nov 2015

No

No

Belgium: 12

Korea, Republic of: 32

United States: 11

Poland: 3

Netherlands: 6

64

21

0

0

0

0

0

0

35

28

1

Overall Study (overall period)

Not applicable

Yes

Durvalumab

MEDI4736

Solution for infusion

Intravenous use

Retreatment Phase (MEDI): Durvalumab 1.5 g via IV infusion q4w for up to a total of 12 months (13 doses). Retreatment Phase (COMBO): Durvalumab 1.5 g via IV infusion q4w (in combination with tremelimumab 75 mg) for up to 4 doses, followed by durvalumab 1.5 g via IV infusion q4w for up to a total of 8 months (9 additional doses).

Tremelimumab

Solution for infusion

Intravenous use

Monotherapy Phase: Tremelimumab 750 milligrams (mg) via intravenous (IV) infusion once every 4 weeks (q4w) for 7 doses (cycles), then every 12 weeks (q12w) for 2 additional cycles for up to a total of 12 months or until confirmed PD. Retreatment Phase (COMBO): Tremelimumab 75 mg via IV infusion q4w for up to 4 doses (in combination with durvalumab 1.5 g).

Durvalumab

MEDI4736

Solution for infusion

Intravenous use

Retreatment Phase (COMBO): Durvalumab 1.5 g via IV infusion q4w (in combination with tremelimumab 75 mg) for up to 4 doses, followed by durvalumab 1.5 g via IV infusion q4w for up to a total of 8 months (9 additional doses).

Tremelimumab

Solution for infusion

Intravenous use

Monotherapy Phase: Tremelimumab 750 mg via IV infusion q4w for 7 doses, then q12w for 2 additional doses for up to a total of 12 months or until confirmed PD. Retreatment Phase (COMBO): Tremelimumab 75 mg via IV infusion q4w for up to 4 doses (in combination with durvalumab 1.5 g).

Durvalumab

MEDI4736

Solution for infusion

Intravenous use

Retreatment Phase (MEDI): Durvalumab 1.5 g via IV infusion q4w for up to a total of 12 months (13 doses). Retreatment Phase (COMBO): Durvalumab 1.5 g via IV infusion q4w (in combination with tremelimumab 75 mg) for up to 4 doses, followed by durvalumab 1.5 g via IV infusion q4w for up to a total of 8 months (9 additional doses).

Tremelimumab

Solution for infusion

Intravenous use

Monotherapy Phase: Tremelimumab 750 mg via IV infusion q4w for 7 doses, then q12w for 2 additional doses for up to a total of 12 months or until confirmed PD. Retreatment Phase (COMBO): Tremelimumab 75 mg via IV infusion q4w for up to 4 doses (in combination with durvalumab 1.5 g).

UBC Cohort

TNBC Cohort

PDAC Cohort

UBC Cohort

TNBC Cohort

PDAC Cohort

UBC - Tremelimumab Monotherapy

Patients with UBC were administered tremelimumab via IV infusion at a dose of 750 mg q4w for 7 cycles, then q12w for 2 additional cycles, for up to a total of 12 months or until confirmed PD.

TNBC - Tremelimumab Monotherapy

Patients with TNBC were administered tremelimumab via IV infusion at a dose of 750 mg q4w for 7 cycles, then q12w for 2 additional cycles, for up to a total of 12 months or until confirmed PD.

PDAC - Tremelimumab Monotherapy

Patients with PDAC were administered tremelimumab via IV infusion at a dose of 750 mg q4w for 7 cycles, then q12w for 2 additional cycles, for up to a total of 12 months or until confirmed PD.

UBC - COMBO

Eligible UBC patients with confirmed PD on tremelimumab monotherapy or during the follow-up period were sequenced to receive durvalumab + tremelimumab combination therapy (also referred to as COMBO; durvalumab 1.5 g via IV infusion q4w in combination with tremelimumab 75 mg via IV infusion q4w for up to 4 cycles each, followed by durvalumab 1.5 g via IV infusion q4w) for up to a total of 8 months.

TNBC - COMBO

Eligible TNBC patients with confirmed PD on tremelimumab monotherapy or during the follow-up period were sequenced to receive durvalumab + tremelimumab combination therapy (also referred to as COMBO; durvalumab 1.5 g via IV infusion q4w in combination with tremelimumab 75 mg via IV infusion q4w for up to 4 cycles each, followed by durvalumab 1.5 g via IV infusion q4w) for up to a total of 8 months.

PDAC - COMBO

Eligible PDAC patients with confirmed PD on tremelimumab monotherapy or during the follow-up period were sequenced to receive durvalumab + tremelimumab combination therapy (also referred to as COMBO; durvalumab 1.5 g via IV infusion q4w in combination with tremelimumab 75 mg via IV infusion q4w for up to 4 cycles each, followed by durvalumab 1.5 g via IV infusion q4w) for up to a total of 8 months.

UBC- MEDI

Eligible UBC patients with confirmed PD on tremelimumab monotherapy or during the follow-up period were sequenced to receive durvalumab monotherapy (also referred to as MEDI; 1.5 g via IV infusion q4w) for up to a total of 12 months.

PDAC - MEDI

Eligible PDAC patients with confirmed PD on tremelimumab monotherapy or during the follow-up period were sequenced to receive durvalumab monotherapy (also referred to as MEDI; 1.5 g via IV infusion q4w) for up to a total of 12 months.

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

Primary

From baseline to 12 months in the tremelimumab monotherapy phase

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. Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy). DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.

Secondary

From baseline to 12 months in the tremelimumab monotherapy phase

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

Secondary

From baseline to 12 months in the tremelimumab monotherapy phase

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

Secondary

From baseline to 12 months in the tremelimumab monotherapy phase

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

Secondary

From baseline to 12 months in the tremelimumab monotherapy phase

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

Secondary

From baseline to primary data cut-off date

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. 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).

Secondary

From baseline to 12 months in retreatment phase

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. 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 was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.

Secondary

From baseline to 12 months in retreatment phase

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. 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).

Secondary

From baseline to 4 months in retreatment phase

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. 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).

Secondary

From baseline to 12 months in retreatment phase

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). 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).

Secondary

From baseline to 12 months in retreatment phase

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. 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).

Secondary

From baseline in retreatment phase to primary data cut-off date

Adverse events were collected from Day 1 (i.e. first dose) up until 90 days following the end of treatment in the tremelimumab monotherapy phase and the retreatment phase (up to a total of 15 months per treatment phase).

21.0

TNBC - Tremelimumab Monotherapy

PDAC- Tremelimumab Monotherapy

UBC - COMBO

UBC- Tremelimumab Monotherapy

UBC- MEDI

TNBC - COMBO

PDAC - COMBO

PDAC - MEDI