Durvalumab and Tremelimumab for Pediatric Malignancies

Phase I/II, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Durvalumab Monotherapy or in Combination With Tremelimumab in Pediatric Patients With Advanced Solid Tumors and Hematological Malignancies.

The purpose of the study is to determine the recommended dose of durvalumab and tremelimumab (immunotherapy drugs) in pediatric patients with advanced solid and hematological cancers and expand in a second phase to test the efficacy of these drugs once this dose is determined.

Study Overview

• Status: Active, not recruiting
• Conditions: Pediatric Cancer; Hematological Malignancies; Solid Tumor Pediatric
• Intervention / Treatment: Drug: Durvalumab / Tremelimumab Combination Therapy

Detailed Description

This is a first time in pediatrics study primarily designed to evaluate the safety and tolerability of durvalumab and durvalumab in combination with tremelimumab at increasing doses in pediatric patients with advanced solid malignancies and hematological malignancies (including lymphomas) and for whom no standard of care treatments exist. Although treatment efficacy is not a primary objective of this study given its early phase nature, the patients screened for this study have no curative options and this study offers the potential of some benefit.

The study will also characterize the PK of durvalumab and durvalumab in combination with tremelimumab in children and adolescents and explore potential biological activity and immunogenicity by assessing pharmacodynamics, anti drug antibody (ADA) levels, and anti-tumor activity. The results from this trial will form the basis for decisions for potential future pediatric studies

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Lille, France, 59020
    • Research Site
  • Marseille, France, 13385
    • Research Site
  • Paris, France, 75248
    • Research Site
• Germany
  • Cologne, Germany, 50924
    • Research Site
• Italy
  • Genova, Italy, 16100
    • Research Site
  • Milan, Italy, 20133
    • Research Site
  • Rome, Italy, 00165
    • Research Site
  • Torino, Italy, 10126
    • Research Site
• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Madrid, Spain, 28009
    • Research Site
• United Kingdom
  • Leeds, United Kingdom, LS1 3EX
    • Research Site
  • London, United Kingdom, WC1N 3JH
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
  • New York
    • New Hyde Park, New York, United States, 11040
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Max Age =17 years
• Solid Tumors (except primary central nervous system malignant tumors): Patients must have a histopathologic confirmation of malignancy. Patients must have progressed or are refractory to standard therapies, and for whom no standard of care treatments exist
• Non-Hodgkin's Lymphoma, limited to primary mediastinal B-cell lymphoma and anaplastic large cell lymphoma. Patients must have progressed or are refractory to standard therapies, and for whom no standard of care treatments exist.
• Provision of diagnostic tumor sample mandated if available
• Evaluable disease
• No prior exposure to immune-mediated therapy
• Adequate organ and marrow function
• Life expectancy of at least 3 months

Exclusion Criteria:

• History of allogeneic organ transplantation (exceptions may be allowed for NHL after discussion with Sponsor). History of autologous bone marrow transplant may be allowed (after discussion with Sponsor).
• Active or prior documented autoimmune or inflammatory disorders (exceptions)
• Uncontrolled intercurrent illness
• History of primary immunodeficiency
• Active infection including tuberculosis, hepatitis B, C or HIV
• Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer therapy (exceptions)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Durvalumab / Tremelimumab Combination Therapy; Part 1 (dose finding) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are initially administered at dose level 1 and dose escalated based on results from PK modeling and tolerance to determine the RP2D. Both drugs are administered every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvavalumab for 4 doses, from cycles 2-5. (sarcoma, NB and NHL) Part 2 (dose expansion phase) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are administered at the RP2D, every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvalumab for 4 doses, from cycles 1-4. Tremelimumab may be added for 4 doses at time of progressive disease. Cohorts: solid tumors, sarcomas, NHL restricted to PMBCL and ALCL subtypes)

Drug: Durvalumab / Tremelimumab Combination Therapy; Starting dose: durvalumab: 20mg/kg tremelimumab: 1mg/kg at cycles 2 to 5 only co-administered with durvalumab. The Recommended Phase 2 dose will be used for the dose expansion phase.; Other Names: durvalumab: Imfinzi, MEDI4736; tremelimumab: CP-675,206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Minimum Serum Concentration (Cmin) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Area Under the Serum Concentration-Time Curve (AUC) From Zero to 14 (AUC 0-14) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Finding Phase: AUC From Zero to 28 (AUC 0-28) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Finding Phase: Time to Cmax (Tmax) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Apparent Terminal Elimination Half-life Associated With the Terminal Slope of the Semi-logarithmic Concentration Time Curve (t½λz) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Dose-Normalized AUC (0-14) (AUC [0-14]/D) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC(0-14)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Finding Phase: Dose-Normalized AUC (0-28) (AUC [0-28]/D) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC(0-28)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Finding Phase: Dose-Normalized Cmax (Cmax/D) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 6, 8, 10 and 12
Dose-Finding Phase: Cmax of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: Cmin of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: (AUC 0-14) of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, and Cycle 2 Day 8
Dose-Finding Phase: (AUC 0-28) of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15
Dose-Finding Phase: Tmax of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: T½λz of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: AUC (0-14)/D of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC(0-14)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1 and Cycle 2 Day 8
Dose-Finding Phase: AUC (0-28)/D of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC(0-28)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15
Dose-Finding Phase: Cmax/D of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, pre-infusion and post-infusion in Cycle 3, 4, and 5
Dose-Finding Phase: Number of Participants With Adverse Events (AE), Serious AE (SAE), AE Leading to Discontinuation of Durvalumab and Tremelimumab, AE of Special Interest (AESI) or AE of Possible Interest (AEPI) Related to Durvalumab and Tremelimumab	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Some AEs and higher-level terms were considered AESI or AEPIs and this list of categories were provided by the patient safety team.	From Day 1 up to 15 months
Dose-Expansion Phase Only: Objective Response Rate (ORR)	ORR as per RECIST 1.1 was defined as the percentage of participants with at least 1 investigator-assessed visit response of complete response (CR) or partial response (PR) that was subsequently confirmed on another scan not less than 4 weeks after visit observed response. CR was defined as disappearance of all target lesions (TLs), any pathological lymph nodes selected as TLs with reduction in short axis to < 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference to baseline sum of diameters as long as criteria for PD are not met.	From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Duration of Response (DOR)	Duration of response was the time from the first documentation of CR/PR (which was subsequently confirmed) until the date of documented progression, or death which coincides with the progression free survival (PFS) endpoint. For participants who did not progress following a response, the DOR was censored during the PFS censoring time. It was calculated using Kaplan-Meier technique.	From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Best Objective Response (BOR)	BOR was calculated based on the overall visit responses from each RECIST 1.1 assessment. Categorization of BOR for solid tumors were based on RECIST 1.1 using the following response categories: CR, PR, stable disease (SD), progression of disease (PD), and not evaluable (NE). CR: disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to <10 mm. PR: 30% decrease in the sum of diameters of TLs. SD: Neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increased to qualify for PD. PD: >= 20 % increase in the sum of diameters to TLs and an increase of >= 5 mm. NE: Only relevant if any of the TLs were not assessed or NE or had a lesion intervention at visit. Non-CR/Non-PD: Persistence of 1+ non-target lesion (s). Non-CR/non-PD was relevant to participants who did not have measurable disease at baseline.	From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Disease Control Rate (DCR)	DCR was defined as the percentage of participants who achieved a BOR of unconfirmed CR or PR, respectively, or who had SD. CR was defined as disappearance of all TLs, any pathological lymph nodes selected as TLs with reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference to baseline sum of diameters as long as criteria for PD are not met. SD: Neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increased to qualify for PD.	At 16 and 24 Weeks
Dose-Expansion Phase Only: PFS	PFS as per RECIST 1.1 was defined as the time from the date of first dose of study treatment until the date of objective disease progression or death by any cause in the absence of progression, regardless of whether the participant withdrew from study therapy or received another anti-cancer therapy prior to progression (date of PFS event or censoring - date of first dose + 1). Confidence interval was calculated using Kaplan-Meier technique.	From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Overall Survival (OS)	OS was defined as the time from the date of first dose of study treatment until death due to any cause regardless of whether the patient withdraws from study treatment or received another anti-cancer therapy (i.e date of death or censoring - date of first dose + 1).	From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Dose-Expansion Phase Only: Survival Rate at 12 Months and 24 Months	Survival rates were defined as the Kaplan-Meier estimate of OS at 12 and 24 months.	At 12 and 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Expansion Phase: Cmax of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 8, and 12
Dose-Expansion Phase: Cmin of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 8, and 12
Dose-Expansion Phase: AUC (0-14) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Expansion Phase: AUC (0-28) of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Expansion Phase: Tmax of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 8, and 12
Dose-Expansion Phase: T½λz of Durvalumab	Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 8, and 12
Dose-Expansion Phase: AUC (0-14)/D of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-14)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Expansion Phase: AUC (0-28)/D of Durvalumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-28)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Expansion Phase: Cmax/D of Durvalumab	Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, pre-infusion and post-infusion in Cycle 3, 4, 8, and 12
Dose-Expansion Phase: Cmax of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 3 Day 1 pre-infusion and post-infusion on Cycle 4
Dose-Expansion Phase: Cmin of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 3 Day 1 pre-infusion and post-infusion on Cycle 4
Dose-Expansion Phase: AUC (0-14) of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Expansion Phase: AUC (0-28) of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Expansion Phase: Tmax of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 3 Day 1 pre-infusion and post-infusion on Cycle 4
Dose-Expansion Phase: T½λz of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 3 Day 1 pre-infusion and post-infusion on Cycle 4
Dose-Expansion Phase: AUC (0-14)/D of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-14)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Dose-Expansion Phase: AUC (0-28)/D of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. AUC (0-28)/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Dose-Expansion Phase: Cmax/D of Tremelimumab	Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.	Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 3 Day 1 pre-infusion and post-infusion on Cycle 4
Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs)	ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Persistently positive was defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.	Pre-infusion on Cycle 1 Day 1 and Cycle 3 Day 1 (durvalumab and tremelimumab), pre-infusion on Cycle 2 Day 1, Cycle 5 Day 1 and Cycle 8 Day 1 for tremelimumab
Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs	ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Persistently positive was defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. The category includes participants meeting these criteria who are ADA positive at baseline. Transiently positive was defined as having at least 1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The category includes participants meeting these criteria who are ADA positive at baseline.	Pre-infusion on Cycle 1 Day 1 and Cycle 3 Day 1 (durvalumab and tremelimumab) and random sample on Cycle 7 Day 1 for tremelimumab
Number of Participants With Individual Antibody Titer Measurement	Blood samples were planned to be collected for vaccine antibody titer measurements before and after planned routine immunization.	Pre-infusion on Cycle 1 Day 1 and Cycle 4 Day 1 for durvalumab, pre-infusion on Cycle 1 Day 1, pre-infusion on Cycle 3, 4, and 8 Day 1 for tremelimumab (dose-expansion)
Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67	Blood samples were collected at indicated timepoints for flow cytometry assessment. Cycle (C) and Day (D). Data collected for the flow cytometry analysis from the participants enrolled in both the dose finding and dose expansion phase were analyzed in the context of the dosing regimen received, to determine any potential differences in the immune response based on the durvalumab dose.	Pre-dose Cycle 1 Day 8, pre-dose Cycle 2 Day 1, Cycle 2 Day 8, pre-dose Cycle 3 Day 1 (Dose-finding); Pre-dose Cycle 1 Day 1, Cycle 1 Day 8, pre-dose Cycle 2 Day 1 (Dose-expansion)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Ashok Gupta, MD, PhD, AstraZeneca Global Medicines Development, Academy House

Publications and helpful links

Helpful Links

• Study Protocol
• CSR Synopsis Redacted
• SAP Redacted

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2019
• Primary Completion (Actual): February 28, 2023
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: February 8, 2019
• First Posted (Actual): February 12, 2019

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms; Hematologic Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; durvalumab; tremelimumab
• Other Study ID Numbers: D419EC00001; 2018-003118-42 (EudraCT Number); 2023-510424-68-00 (Registry Identifier: CTIS (EU))

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
• product manufactured in and exported from the U.S.: Yes