Study of Tremelimumab in Patients With Advanced Solid Tumors

A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients With Advanced Solid Tumors

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

Study Overview

• Status: Completed
• Conditions: Pancreatic Ductal Adenocarcinoma; Triple-negative Breast Cancer; Urothelial Bladder Cancer
• Intervention / Treatment: Biological: Tremelimumab monotherapy; Biological: MEDI4736 monotherapy; Biological: MEDI4736 + tremelimumab combination therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Research Site
  • Charleroi, Belgium, 6000
    • Research Site
  • Wilrijk, Belgium, 2610
    • Research Site
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Research Site
  • Utrecht, Netherlands, 3584 CX
    • Research Site
• Poland
  • Gdańsk, Poland, 80-214
    • Research Site
  • Łódź, Poland, 93-513
    • Research Site
• United States
  • California
    • San Francisco, California, United States, 94158
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 150 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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:

1. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treme mono to be sequenced to MEDI4736 mono or combination; tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD)	Biological: Tremelimumab monotherapy; IV infusion; Biological: MEDI4736 monotherapy; IV infusion; Biological: MEDI4736 + tremelimumab combination therapy; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Confirmed Overall Response During 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.	From baseline to 12 months in the tremelimumab monotherapy phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Duration of Response (DoR) During 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.	From baseline to 12 months in the tremelimumab monotherapy phase
Disease Control Rate (DCR) During 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.	From baseline to 12 months in the tremelimumab monotherapy phase
Median PFS During 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.	From baseline to 12 months in the tremelimumab monotherapy phase
Best Objective Response (BoR) During 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).	From baseline to 12 months in the tremelimumab monotherapy phase
Median Overall Survival (OS) During 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.	From baseline to final data cut-off date
Percentage of Patients With Confirmed Overall Response During 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.	From baseline to 12 months in retreatment phase
Median DoR During 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.	From baseline to 12 months in retreatment phase
DCR During 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.	From baseline to 4 months in retreatment phase
Median PFS During 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.	From baseline to 12 months in retreatment phase
BoR During 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).	From baseline to 12 months in retreatment phase
Median OS During 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.	From baseline in retreatment phase to final data cut-off date

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Sharma Padmanee, MD, PhD, Anderson Cancer Center, the University of Texas

Publications and helpful links

Helpful Links

• Related Info
• Related Info
• Redacted CSR synopsis

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2015
• Primary Completion (Actual): February 17, 2018
• Study Completion (Actual): March 28, 2023

Study Registration Dates

• First Submitted: August 12, 2015
• First Submitted That Met QC Criteria: August 18, 2015
• First Posted (Estimated): August 19, 2015

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Urothelial bladder cancer, Triple-negative breast cancer, Pancreatic ductal adenocarcinoma, Advanced Solid Tumors, Tremelimumab, MEDI4736, ORR
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Breast Diseases; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Adenocarcinoma; Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab; Antibodies, Monoclonal
• Other Study ID Numbers: D4884C00001; 2015-002934-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No