Pediatric CancerPhase 1/2NCT03837899
Durvalumab and Tremelimumab for Pediatric Malignancies
A Phase 1/2 study testing Durvalumab / Tremelimumab Combination Therapy in people with Pediatric Cancer and Solid Tumor Pediatric, run by AstraZeneca at 19 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 18 years
- Conditions the study is for
- Pediatric Cancer, Solid Tumor Pediatric, Hematological Malignancies
- What is being tested?
- Durvalumab / Tremelimumab Combination Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 19 sitesin 7 countries
- Study dates
- 7 Mar 2019to 31 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
19 sites in 7 countries.
19 sites in 7 countries
United States5 sites
Research Site
Baltimore, Maryland, 21231
Research Site
Boston, Massachusetts, 02115
Research Site
Charleston, South Carolina, 29425
Research Site
New Hyde Park, New York, 11040
Research Site
Oklahoma City, Oklahoma, 73104
Italy4 sites
Research Site
Genova, 16100
Research Site
Milan, 20133
Research Site
Rome, 00165
Research Site
Torino, 10126
France3 sites
Research Site
Lille, 59020
Research Site
Marseille, 13385
Research Site
Paris, 75248
United Kingdom3 sites
Research Site
Leeds, LS1 3EX
Research Site
London, WC1N 3JH
Research Site
Sutton, SM2 5PT
About this study
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.
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.
Read the 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
- Being tested
- Durvalumab / Tremelimumab Combination Therapy
- Keywords
- Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
- Medical subject headings
- Neoplasms, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Durvalumab / Tremelimumab Combination TherapyDrug
Also called durvalumab: Imfinzi, MEDI4736, tremelimumab: CP-675,206
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.
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab / Tremelimumab Combination Therapy | Experimental | 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) Receives: Drug: Durvalumab / Tremelimumab Combination Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: At 12 and 24 Weeks
Secondary outcomes (22)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2019
- Study start7 Mar 2019
- Primary completion28 Feb 2023
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pediatric CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ashok Gupta, MD, PhD, Study director, AstraZeneca Global Medicines Development, Academy House
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03837899
- Sponsor's protocol ID
- D419EC00001
- Other IDs
- 2023-510424-68-00, 2018-003118-42, 2018, 2023
- Status last verified
- Sep 2026
- First submitted
- 24 Jan 2019
- Last updated
- 29 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Hargrave D, Marshall LV, Andre N, Krystal J, Ladle BH, Robbins KA, Hois S, Armstrong J, Donegan S. Phase I/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors. Front Oncol. 2026 May 15;16:1680081. doi: 10.3389/fonc.2026.1680081. eCollection 2026.
PubMed 42222420
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03837899
- Acronym / sponsor ID
- D419EC00001
- Keywords
- Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 7 Mar 2019 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 12 Feb 2019 (actual)
- Results
- Posted 19 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Durvalumab / Tremelimumab Combination Therapy | Experimental | Drug: Durvalumab / Tremelimumab Combination TherapyPart 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) |
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Durvalumab / Tremelimumab Combination TherapyAlso: durvalumab: Imfinzi, MEDI4736, tremelimumab: CP-675,206Starting 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. | Drug | Durvalumab / Tremelimumab Combination Therapy |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
22 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42222420Hargrave D, Marshall LV, Andre N, Krystal J, Ladle BH, Robbins KA, Hois S, Armstrong J, Donegan S. Phase I/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors. Front Oncol. 2026 May 15;16:1680081. doi: 10.3389/fonc.2026.1680081. eCollection 2026.
- Study ProtocolLink provided by the sponsor.
- CSR Synopsis RedactedLink provided by the sponsor.
- SAP RedactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Knowledge, Attitudes, Practice
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashok Gupta, MD, PhD study director
AstraZeneca Global Medicines Development, Academy House
19 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Durvalumab / Tremelimumab Combination Therapy in people with Pediatric Cancer and Solid Tumor Pediatric, run by AstraZeneca at 19 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Italy, France, United Kingdom, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 26 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03837899, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.