Durvalumab and Tremelimumab for Pediatric Malignancies

• ClinicalTrials.gov Identifier: NCT03837899
• Recruitment Status: Active, not recruiting
• First Posted: February 12, 2019
• Results First Posted: March 19, 2024
• Last Update Posted: March 19, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pediatric Cancer; Solid Tumor Pediatric; Hematological Malignancies	Drug: Durvalumab / Tremelimumab Combination Therapy	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: March 7, 2019
• Actual Primary Completion Date: February 28, 2023
• Estimated Study Completion Date: December 30, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.
2. Dose-Finding Phase: Minimum Serum Concentration (Cmin) of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.
3. Dose-Finding Phase: Area Under the Serum Concentration-Time Curve (AUC) From Zero to 14 (AUC 0-14) of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8 ]
   Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.
4. Dose-Finding Phase: AUC From Zero to 28 (AUC 0-28) of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15 ]
   Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.
5. Dose-Finding Phase: Time to Cmax (Tmax) of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.
6. Dose-Finding Phase: Apparent Terminal Elimination Half-life Associated With the Terminal Slope of the Semi-logarithmic Concentration Time Curve (t½λz) of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.
7. Dose-Finding Phase: Dose-Normalized AUC (0-14) (AUC [0-14]/D) of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8 ]
   Serum samples were collected from the participants at the defined timepoints. AUC(0-14)/D was determined using standard non-compartmental methods.
8. Dose-Finding Phase: Dose-Normalized AUC (0-28) (AUC [0-28]/D) of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15 ]
   Serum samples were collected from the participants at the defined timepoints. AUC(0-28)/D was determined using standard non-compartmental methods.
9. Dose-Finding Phase: Dose-Normalized Cmax (Cmax/D) of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.
10. Dose-Finding Phase: Cmax of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.
11. Dose-Finding Phase: Cmin of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.
12. Dose-Finding Phase: (AUC 0-14) of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 2 Day 1, and Cycle 2 Day 8 ]
    Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.
13. Dose-Finding Phase: (AUC 0-28) of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15 ]
    Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.
14. Dose-Finding Phase: Tmax of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.
15. Dose-Finding Phase: T½λz of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.
16. Dose-Finding Phase: AUC (0-14)/D of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 2 Day 1 and Cycle 2 Day 8 ]
    Serum samples were collected from the participants at the defined timepoints. AUC(0-14)/D was determined using standard non-compartmental methods.
17. Dose-Finding Phase: AUC (0-28)/D of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15 ]
    Serum samples were collected from the participants at the defined timepoints. AUC(0-28)/D was determined using standard non-compartmental methods.
18. Dose-Finding Phase: Cmax/D of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.
19. 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 [ Time Frame: From Day 1 up to 15 months ]
    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.
20. Dose-Expansion Phase Only: Objective Response Rate (ORR) [ Time Frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023) ]
    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.
21. Dose-Expansion Phase Only: Duration of Response (DOR) [ Time Frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023) ]
    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.
22. Dose-Expansion Phase Only: Best Objective Response (BOR) [ Time Frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023) ]
    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.
23. Dose-Expansion Phase Only: Disease Control Rate (DCR) [ Time Frame: At 16 and 24 Weeks ]
    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.
24. Dose-Expansion Phase Only: PFS [ Time Frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023) ]
    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.
25. Dose-Expansion Phase Only: Overall Survival (OS) [ Time Frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023) ]
    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).
26. Dose-Expansion Phase Only: Survival Rate at 12 Months and 24 Months [ Time Frame: At 12 and 24 Weeks ]
    Survival rates were defined as the Kaplan-Meier estimate of OS at 12 and 24 months.

Secondary Outcome Measures :

1. Dose-Expansion Phase: Cmax of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.
2. Dose-Expansion Phase: Cmin of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.
3. Dose-Expansion Phase: AUC (0-14) of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8 ]
   Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.
4. Dose-Expansion Phase: AUC (0-28) of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15 ]
   Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.
5. Dose-Expansion Phase: Tmax of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.
6. Dose-Expansion Phase: T½λz of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.
7. Dose-Expansion Phase: AUC (0-14)/D of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8 ]
   Serum samples were collected from the participants at the defined timepoints. AUC (0-14)/D was determined using standard non-compartmental methods.
8. Dose-Expansion Phase: AUC (0-28)/D of Durvalumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15 ]
   Serum samples were collected from the participants at the defined timepoints. AUC (0-28)/D was determined using standard non-compartmental methods.
9. Dose-Expansion Phase: Cmax/D of Durvalumab [ Time Frame: 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 ]
   Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.
10. Dose-Expansion Phase: Cmax of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods.
11. Dose-Expansion Phase: Cmin of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods.
12. Dose-Expansion Phase: AUC (0-14) of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8 ]
    Serum samples were collected from the participants at the defined timepoints. AUC (0-14) was determined using standard non-compartmental methods.
13. Dose-Expansion Phase: AUC (0-28) of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15 ]
    Serum samples were collected from the participants at the defined timepoints. AUC (0-28) was determined using standard non-compartmental methods.
14. Dose-Expansion Phase: Tmax of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods.
15. Dose-Expansion Phase: T½λz of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods.
16. Dose-Expansion Phase: AUC (0-14)/D of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8 ]
    Serum samples were collected from the participants at the defined timepoints. AUC (0-14)/D was determined using standard non-compartmental methods.
17. Dose-Expansion Phase: AUC (0-28)/D of Tremelimumab [ Time Frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15 ]
    Serum samples were collected from the participants at the defined timepoints. AUC (0-28)/D was determined using standard non-compartmental methods.
18. Dose-Expansion Phase: Cmax/D of Tremelimumab [ Time Frame: 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 ]
    Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods.
19. Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) [ Time Frame: 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 ]
    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.
20. Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs [ Time Frame: 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 ]
    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.
21. Number of Participants With Individual Antibody Titer Measurement [ Time Frame: 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) ]
    Blood samples were planned to be collected for vaccine antibody titer measurements before and after planned routine immunization.
22. Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 [ Time Frame: 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) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 0 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, Maryland

Research Site

Baltimore, Maryland, United States, 21231

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02115

United States, New York

Research Site

New Hyde Park, New York, United States, 11040

United States, Oklahoma

Research Site

Oklahoma City, Oklahoma, United States, 73104

United States, South Carolina

Research Site

Charleston, South Carolina, United States, 29425

France

Research Site

Lille Cedex, France, 59020

Research Site

Marseille, France, 13385

Research Site

Paris Cedex 05, France, 75248

Germany

Research Site

Köln, Germany, 50924

Italy

Research Site

Genova, Italy, 16100

Research Site

Milano, Italy, 20133

Research Site

Rome, Italy, 00165

Research Site

Torino, Italy, 10126

Netherlands

Research Site

Utrecht, Netherlands, 3584 CS

Spain

Research Site

Barcelona, Spain, 08035

Research Site

Madrid, Spain, 28009

United Kingdom

Research Site

Leeds, United Kingdom, LS1 3EX

Research Site

London, United Kingdom, WC1N 3JH

Research Site

Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

AstraZeneca

Investigators

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

  Study Documents (Full-Text)

Documents provided by AstraZeneca:

Study Protocol  [PDF] December 12, 2022

Statistical Analysis Plan  [PDF] April 19, 2023

More Information

Additional Information:

Study Protocol 

CSR Synopsis Redacted 

SAP Redacted 

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03837899
• Other Study ID Numbers: D419EC00001; 2018-003118-42 ( EudraCT Number )
• First Posted: February 12, 2019
• Results First Posted: March 19, 2024
• Last Update Posted: March 19, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• 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
• 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
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• 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

Keywords provided by AstraZeneca:

Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy

Additional relevant MeSH terms:

Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Hematologic Diseases; Durvalumab; Tremelimumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs