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Durvalumab / Tremelimumab Combination Therapy

Phase 1

Pediatric Cancer | Small molecule | Oncology |AstraZeneca PLC|Last Updated: Apr 21, 2026

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
UNCONTROLLEDDMC
Total Trials1
Total Enrollment50
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03837899Durvalumab and Tremelimumab for Pediatric MalignanciesPHASE1 ACTIVE NOT_RECRUITING 50Mar 7, 2019Dec 31, 2026Apr 21, 202619 United States, France +5
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Study Endpoints
Primary Endpoints
Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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)
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)
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
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)
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
At 12 and 24 Weeks

Survival rates were defined as the Kaplan-Meier estimate of OS at 12 and 24 months.

Secondary Endpoints
Dose-Expansion Phase: Cmax of Durvalumab
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
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
Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Durvalumab / Tremelimumab Combination TherapyEXPERIMENTALPart 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)
Interventions
NameTypeDescription
Durvalumab / Tremelimumab Combination TherapyDRUGStarting 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.
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Eligibility Criteria
Age Range0 Years — 18 Years
SexALL
Healthy VolunteersNo
Study Sites19

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 ...

Countries:United StatesFranceGermanyItalyNetherlandsSpainUnited Kingdom
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Recent Changes (Last 90 Days)
MEDIUMMay 26, 2026NCT03837899primaryCompletionDate: changed
LOWMay 24, 2026NCT03837899studyFirstPostDate: changed