Study of Tremelimumab in Patients With Advanced Solid Tumors

Phase 2

Completed

Conditions: Pancreatic Ductal Adenocarcinoma
Urothelial Bladder Cancer
Triple-negative Breast Cancer

Interventions: Biological: Tremelimumab monotherapy
Biological: MEDI4736 monotherapy
Biological: MEDI4736 + tremelimumab combination therapy

Registration Number: NCT02527434

Lead Sponsor: AstraZeneca

Brief Summary: A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients with Advanced Solid Tumors

Detailed Description: This is an open-label, multi-center study to determine the efficacy and safety of tremelimumab in the treatment of different cohorts of patients with selected advanced solid tumors. If eligible and at the discretion of the Investigator, after confirmed disease progression on tremelimumab monotherapy or during follow-up, patients will have the option of being sequenced to MEDI4736 (MedImmune 4736) monotherapy or MEDI4736 + tremelimumab combination therapy, for up to 12 months or until disease progression, whichever comes sooner.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 64

Inclusion Criteria

histologically or cytologically documented solid tumor malignancies, including but not limited to 1 of the following: UBC, Metastatic PDAC, TNBC; Are intolerant, are ineligible for, or have refused treatment with standard first-line therapy; 2. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scans and that is suitable for accurate repeated measurements.

Exclusion criteria:

Any concurrent chemotherapy, biologic, or hormonal therapy for cancer Treatment; 2. History of leptomeningeal carcinomatosis; 3. Active or prior documented autoimmune or inflammatory disorders; 4. Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 14 days prior to study treatment start; 5. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms; 6. Known allergy or hypersensitivity to IP or any IP excipient

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treme mono to be sequenced to MEDI4736 mono or combination	Tremelimumab monotherapy	tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD)
treme mono to be sequenced to MEDI4736 mono or combination	MEDI4736 + tremelimumab combination therapy	tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD)
treme mono to be sequenced to MEDI4736 mono or combination	MEDI4736 monotherapy	tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD)

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With Confirmed Overall Response During Tremelimumab Monotherapy Phase	From baseline to 12 months in the tremelimumab monotherapy phase	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.

Secondary Outcome Measures

Name	Time	Method
Median DoR During Retreatment Phase	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. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.
Median Duration of Response (DoR) During Tremelimumab Monotherapy Phase	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. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.
Disease Control Rate (DCR) During Tremelimumab Monotherapy Phase	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.
Median Overall Survival (OS) During Tremelimumab Monotherapy Phase	From baseline to final data cut-off date	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.
Percentage of Patients With Confirmed Overall Response During Retreatment Phase	From baseline to 12 months in retreatment phase	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.
DCR During Retreatment Phase	From baseline to 4 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.
Median PFS During Retreatment Phase	From baseline to 12 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.
BoR During Retreatment Phase	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).
Median PFS During Tremelimumab Monotherapy Phase	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.
Best Objective Response (BoR) During Tremelimumab Monotherapy Phase	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).
Median OS During Retreatment Phase	From baseline in retreatment phase to final data cut-off date	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.