Hematological Malignancies, Pediatric Cancer, Solid Tumor Pediatric
Conditions
Keywords
Pediatric, solid tumors, hematological malignancies, durvalumab, tremelimumab, immunotherapy
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.
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
Interventions
DRUGDurvalumab / 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.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Serum samples were collected from the participants at the defined timepoints. Cmax was determined using standard non-compartmental methods. |
| 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 | Serum samples were collected from the participants at the defined timepoints. Cmin was determined using standard non-compartmental methods. |
| Dose-Expansion Phase: 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-Expansion Phase: 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-Expansion Phase: 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, 8, and 12 | Serum samples were collected from the participants at the defined timepoints. Tmax was determined using standard non-compartmental methods. |
| Dose-Expansion Phase: 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, 8, and 12 | Serum samples were collected from the participants at the defined timepoints. T½λz was determined using standard non-compartmental methods. |
| Dose-Expansion Phase: 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-Expansion Phase: 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-Expansion Phase: 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, 8, and 12 | Serum samples were collected from the participants at the defined timepoints. Cmax/D was determined using standard non-compartmental methods. |
| Dose-Expansion Phase: Cmax of Tremelimumab | 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. |
| Dose-Expansion Phase: Cmin of Tremelimumab | 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. |
| Dose-Expansion Phase: AUC (0-14) of Tremelimumab | 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-Expansion Phase: AUC (0-28) of Tremelimumab | 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-Expansion Phase: Tmax of Tremelimumab | 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. |
| Dose-Expansion Phase: T½λz of Tremelimumab | 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. |
| Dose-Expansion Phase: AUC (0-14)/D of Tremelimumab | 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-Expansion Phase: AUC (0-28)/D of Tremelimumab | 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-Expansion Phase: Cmax/D of Tremelimumab | 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. |
| Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | 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. |
| Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | 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. |
| Number of Participants With Individual Antibody Titer Measurement | 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. |
| Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | 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. |
Countries
France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORAshok Gupta, MD, PhD
AstraZeneca Global Medicines Development, Academy House
Participant flow
Recruitment details
This open-label study was conducted in 2 sequential phases: a dose-finding phase (Phase I), followed by a dose-expansion phase (Phase II) in pediatric participants with advanced solid tumors, including sarcoma. Here, results for data analyzed through data cut-off date (DCO) 20-Apr-2023 have been reported.
Pre-assignment details
Each treatment cycle was 28 days. Overall, 33 participants were enrolled in dose-finding phase and 29 participants were administered study treatment. In dose-expansion phase, 23 participants were enrolled and 21 participants were administered study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg Participants who weighed \>= 35 kg were administered durvalumab 20 mg/kg IV in Cycle 1 followed by durvalumab in combination with tremelimumab 1 mg/kg IV in Cycles 2-5 every 28 days. From Cycle 6 onwards participants were administered durvalumab 20 mg/kg every 28 days until clinical or confirmed disease progression or until any of other discontinuation criterion was met, whichever occurred first. | 7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg Participants who weighed \>= 35 kg were administered durvalumab 30 mg/kg IV in Cycle 1 followed by durvalumab in combination with tremelimumab 1 mg/kg IV in Cycles 2-5 every 28 days. From Cycle 6 onwards participants were administered durvalumab 20 mg/kg every 28 days until clinical or confirmed disease progression or until any of other discontinuation criterion was met, whichever occurred first. | 11 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg Participants who weighed \< 35 kg were administered durvalumab 20 mg/kg IV in Cycle 1 followed by durvalumab in combination with tremelimumab 1 mg/kg IV in Cycles 2-5 every 28 days. From Cycle 6 onwards participants were administered durvalumab 20 mg/kg every 28 days until clinical or confirmed disease progression or until any of other discontinuation criterion was met, whichever occurred first. | 3 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg Participants who weighed \< 35 kg were administered durvalumab 30 mg/kg IV in Cycle 1 followed by durvalumab in combination with tremelimumab 1 mg/kg IV in Cycles 2-5 every 28 days. From Cycle 6 onwards participants were administered durvalumab 20 mg/kg every 28 days until clinical or confirmed disease progression or until any of other discontinuation criterion was met, whichever occurred first. | 8 |
| SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg Participants with osteosarcoma and Ewing sarcoma, rhabdomyosarcoma, non rhabdomyosarcoma soft tissue sarcoma, and other sarcomas were included in this arm. Participants were administered durvalumab 30 mg/kg IV in combination with tremelimumab 1 mg/kg IV in Cycles 1-4 every 28 days. From Cycle 5 onwards participants were administered durvalumab 30 mg/kg every 28 days until clinical or confirmed disease progression or until any of other discontinuation criterion was met, whichever occurred first. | 11 |
| STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg Participants with solid tumor other (STO) were included in this arm. Participants were administered durvalumab 30 mg/kg IV in combination with tremelimumab 1 mg/kg IV in Cycles 1-4 every 28 days. From Cycle 5 onwards participants were administered durvalumab 30 mg/kg every 28 days until clinical or confirmed disease progression or until any of other discontinuation criterion was met, whichever came occurred first. | 10 |
| Total | 50 |
Baseline characteristics
| Characteristic | Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Total | STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg |
|---|---|---|---|---|---|---|---|
| Age, Customized 85 years and above | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 6 Participants | 25 Participants | 7 Participants | 4 Participants | 2 Participants | 0 Participants | 6 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 24 Participants | 3 Participants | 7 Participants | 6 Participants | 3 Participants | 5 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 weeks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 7 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 6 Participants | 43 Participants | 8 Participants | 11 Participants | 7 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 10 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 33 Participants | 6 Participants | 8 Participants | 4 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 26 Participants | 5 Participants | 6 Participants | 3 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 24 Participants | 5 Participants | 5 Participants | 5 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 7 | 8 / 11 | 3 / 3 | 7 / 8 | 8 / 11 | 7 / 10 |
| other Total, other adverse events | 6 / 7 | 11 / 11 | 3 / 3 | 7 / 8 | 8 / 11 | 9 / 10 |
| serious Total, serious adverse events | 1 / 7 | 1 / 11 | 0 / 3 | 1 / 8 | 6 / 11 | 3 / 10 |
Outcome results
Primary
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.
Time frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Population: The FAS included all participants who were assigned to treatment and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | SD >= 7 weeks | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | PR | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | PD | 9 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | Unconfirmed complete or partial response | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | Not evaluable | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | CR | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | Not evaluable | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | PR | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | CR | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | Unconfirmed complete or partial response | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | SD >= 7 weeks | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Best Objective Response (BOR) | PD | 7 Participants |
Primary
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.
Time frame: At 16 and 24 Weeks
Population: The FAS included all participants who were assigned to treatment and received at least 1 dose of study treatment. Only participants who achieved a BOR were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Disease Control Rate (DCR) | Week 24 | 9.1 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Disease Control Rate (DCR) | Week 16 | 9.1 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Disease Control Rate (DCR) | Week 24 | 10.0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Disease Control Rate (DCR) | Week 16 | 10.0 percentage of participants |
Primary
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.
Time frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Population: The evaluable for response analysis set is the subset of participants in the FAS who had measurable disease (as per RECIST 1.1) at baseline and had at least 1 follow-up scan measuring all required target lesions and had been followed for at least 3 cycles or measurable disease (as per RECIST 1.1) at baseline and progressed or died in the absence of a follow-up scan. Only responders were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Duration of Response (DOR) | 10.8 months |
Primary
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.
Time frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Population: The evaluable for response analysis set is the subset of participants in the FAS who had measurable disease (as per RECIST 1.1) at baseline and had at least 1 follow-up scan measuring all required target lesions and had been followed for at least 3 cycles or measurable disease (as per RECIST 1.1) at baseline and progressed or died in the absence of a follow-up scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Objective Response Rate (ORR) | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Objective Response Rate (ORR) | 11.1 percentage of participants |
Primary
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).
Time frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Population: The FAS included all participants who were assigned to treatment and received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Overall Survival (OS) | 6.6 months |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Overall Survival (OS) | 6.9 months |
Primary
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.
Time frame: From first dose of study treatment until death or up to approximately 4 years (clinical DCO of 20 Apr 2023)
Population: The FAS included all participants who were assigned to treatment and received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: PFS | 1.7 months |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: PFS | 1.7 months |
Primary
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.
Time frame: At 12 and 24 Weeks
Population: The FAS included all participants who were assigned to treatment and received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Survival Rate at 12 Months and 24 Months | 12 Months | 25.6 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Survival Rate at 12 Months and 24 Months | 24 Months | NA percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Survival Rate at 12 Months and 24 Months | 12 Months | 40.0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase Only: Survival Rate at 12 Months and 24 Months | 24 Months | 30.0 percentage of participants |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Apparent Terminal Elimination Half-life Associated With the Terminal Slope of the Semi-logarithmic Concentration Time Curve (t½λz) of Durvalumab | 16.7 days | Geometric Coefficient of Variation 47.1 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Apparent Terminal Elimination Half-life Associated With the Terminal Slope of the Semi-logarithmic Concentration Time Curve (t½λz) of Durvalumab | 25.3 days | Geometric Coefficient of Variation 56.5 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Apparent Terminal Elimination Half-life Associated With the Terminal Slope of the Semi-logarithmic Concentration Time Curve (t½λz) of Durvalumab | 8.26 days | — |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Apparent Terminal Elimination Half-life Associated With the Terminal Slope of the Semi-logarithmic Concentration Time Curve (t½λz) of Durvalumab | 15.6 days | Geometric Coefficient of Variation 23.3 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Area Under the Serum Concentration-Time Curve (AUC) From Zero to 14 (AUC 0-14) of Durvalumab | 2650 day*mcg/mL | Geometric Coefficient of Variation 61.5 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Area Under the Serum Concentration-Time Curve (AUC) From Zero to 14 (AUC 0-14) of Durvalumab | 5660 day*mcg/mL | Geometric Coefficient of Variation 17.7 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Area Under the Serum Concentration-Time Curve (AUC) From Zero to 14 (AUC 0-14) of Durvalumab | 1830 day*mcg/mL | Geometric Coefficient of Variation 54.7 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Area Under the Serum Concentration-Time Curve (AUC) From Zero to 14 (AUC 0-14) of Durvalumab | 3720 day*mcg/mL | Geometric Coefficient of Variation 46.9 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 2 Day 1 and Cycle 2 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC (0-14)/D of Tremelimumab | 127 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 47.3 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC (0-14)/D of Tremelimumab | 160 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 35.6 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC (0-14)/D of Tremelimumab | 165 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 7 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC (0-14)/D of Tremelimumab | 149 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 20.1 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 2 Day 1, and Cycle 2 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: (AUC 0-14) of Tremelimumab | 127 day*mcg/mL | Geometric Coefficient of Variation 47.3 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: (AUC 0-14) of Tremelimumab | 160 day*mcg/mL | Geometric Coefficient of Variation 35.6 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: (AUC 0-14) of Tremelimumab | 165 day*mcg/mL | Geometric Coefficient of Variation 7 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: (AUC 0-14) of Tremelimumab | 149 day*mcg/mL | Geometric Coefficient of Variation 20.1 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC (0-28)/D of Tremelimumab | 235 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 11.2 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC (0-28)/D of Tremelimumab | 205 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 22.9 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC (0-28)/D of Tremelimumab | 208 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 14.8 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 2 Day 1, Cycle 2 Day 8, and Cycle 2 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: (AUC 0-28) of Tremelimumab | 235 day*mcg/mL | Geometric Coefficient of Variation 11.2 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: (AUC 0-28) of Tremelimumab | 205 day*mcg/mL | Geometric Coefficient of Variation 22.9 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: (AUC 0-28) of Tremelimumab | 208 day*mcg/mL | Geometric Coefficient of Variation 14.8 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC From Zero to 28 (AUC 0-28) of Durvalumab | 3290 day*mcg/mL | Geometric Coefficient of Variation 50.1 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC From Zero to 28 (AUC 0-28) of Durvalumab | 8790 day*mcg/mL | Geometric Coefficient of Variation 13.5 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC From Zero to 28 (AUC 0-28) of Durvalumab | 2500 day*mcg/mL | Geometric Coefficient of Variation 55.4 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: AUC From Zero to 28 (AUC 0-28) of Durvalumab | 6380 day*mcg/mL | Geometric Coefficient of Variation 40.1 |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax/D of Tremelimumab | 19.1 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 73.3 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax/D of Tremelimumab | 24.5 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 44.7 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax/D of Tremelimumab | 39.2 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 68.8 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax/D of Tremelimumab | 23.0 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 31.7 |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax of Tremelimumab | 19.1 mcg/mL | Geometric Coefficient of Variation 73.3 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax of Tremelimumab | 24.5 mcg/mL | Geometric Coefficient of Variation 44.7 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax of Tremelimumab | 39.2 mcg/mL | Geometric Coefficient of Variation 68.8 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmax of Tremelimumab | 23.0 mcg/mL | Geometric Coefficient of Variation 31.7 |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmin of Tremelimumab | 3.71 mcg/mL | Geometric Coefficient of Variation 3.75 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmin of Tremelimumab | 3.45 mcg/mL | Geometric Coefficient of Variation 29.2 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Cmin of Tremelimumab | 3.03 mcg/mL | Geometric Coefficient of Variation 50.3 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-14) (AUC [0-14]/D) of Durvalumab | 132 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 61.5 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-14) (AUC [0-14]/D) of Durvalumab | 189 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 17.7 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-14) (AUC [0-14]/D) of Durvalumab | 91.6 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 54.7 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-14) (AUC [0-14]/D) of Durvalumab | 124 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 46.9 |
Primary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-28) (AUC [0-28]/D) of Durvalumab | 164 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 50.1 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-28) (AUC [0-28]/D) of Durvalumab | 293 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 13.5 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-28) (AUC [0-28]/D) of Durvalumab | 125 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 55.4 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized AUC (0-28) (AUC [0-28]/D) of Durvalumab | 213 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 40.1 |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized Cmax (Cmax/D) of Durvalumab | 18.1 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 58 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized Cmax (Cmax/D) of Durvalumab | 28.8 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 36 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized Cmax (Cmax/D) of Durvalumab | 13.7 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 135 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Dose-Normalized Cmax (Cmax/D) of Durvalumab | 20.4 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 34.2 |
Primary
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.
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
Population: The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study treatment per the clinical study protocol (CSP) for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab | 363 micrograms/ milliliter (mcg/mL) | Geometric Coefficient of Variation 58 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab | 865 micrograms/ milliliter (mcg/mL) | Geometric Coefficient of Variation 36 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab | 275 micrograms/ milliliter (mcg/mL) | Geometric Coefficient of Variation 135 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab | 612 micrograms/ milliliter (mcg/mL) | Geometric Coefficient of Variation 34.2 |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Minimum Serum Concentration (Cmin) of Durvalumab | 48.6 mcg/mL | Geometric Coefficient of Variation 104 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Minimum Serum Concentration (Cmin) of Durvalumab | 169 mcg/mL | Geometric Coefficient of Variation 28.5 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Minimum Serum Concentration (Cmin) of Durvalumab | 21.7 mcg/mL | Geometric Coefficient of Variation 34.6 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Minimum Serum Concentration (Cmin) of Durvalumab | 118 mcg/mL | Geometric Coefficient of Variation 45.4 |
Primary
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.
Time frame: From Day 1 up to 15 months
Population: The Safety analysis set included all participants who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | Any AE | 6 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Tremelimumab | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Tremelimumab | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Durvalumab | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | Any SAE | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Durvalumab | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Durvalumab | 4 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | Any SAE | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Tremelimumab | 2 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Durvalumab | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Tremelimumab | 1 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | Any AE | 11 Participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Durvalumab | 0 Participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | Any AE | 3 Participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | Any SAE | 0 Participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Tremelimumab | 0 Participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Durvalumab | 0 Participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Tremelimumab | 0 Participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Durvalumab | 2 Participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | Any SAE | 1 Participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Durvalumab | 0 Participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | Any AE | 7 Participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AESIs or AEPIs related to Tremelimumab | 1 Participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 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 | AE leading to discontinuation of Tremelimumab | 0 Participants |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: T½λz of Tremelimumab | 16.8 days | Geometric Coefficient of Variation 5.27 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: T½λz of Tremelimumab | 18.7 days | Geometric Coefficient of Variation 20.5 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: T½λz of Tremelimumab | 31.6 days | Geometric Coefficient of Variation 86 |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Time to Cmax (Tmax) of Durvalumab | 0.094 days |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Time to Cmax (Tmax) of Durvalumab | 0.087 days |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Time to Cmax (Tmax) of Durvalumab | 0.09 days |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Time to Cmax (Tmax) of Durvalumab | 0.087 days |
Primary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Tmax of Tremelimumab | 0.046 days |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Tmax of Tremelimumab | 0.051 days |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Tmax of Tremelimumab | 0.040 days |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Tmax of Tremelimumab | 0.046 days |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14)/D of Durvalumab | 141 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 23.2 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14)/D of Durvalumab | 130 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 20 |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14)/D of Tremelimumab | 183 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 65.9 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14)/D of Tremelimumab | 150 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 11.8 |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14) of Durvalumab | 4240 day*mcg/mL | Geometric Coefficient of Variation 23.2 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14) of Durvalumab | 3900 day*mcg/mL | Geometric Coefficient of Variation 20 |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1 and Cycle 1 Day 8
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14) of Tremelimumab | 183 day*mcg/mL | Geometric Coefficient of Variation 65.9 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-14) of Tremelimumab | 150 day*mcg/mL | Geometric Coefficient of Variation 11.8 |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28)/D of Durvalumab | 213 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 23.7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28)/D of Durvalumab | 196 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 25.2 |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28)/D of Tremelimumab | 270 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 58.1 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28)/D of Tremelimumab | 228 (day*mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 12.4 |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28) of Durvalumab | 6400 day*mcg/mL | Geometric Coefficient of Variation 23.7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28) of Durvalumab | 5880 day*mcg/mL | Geometric Coefficient of Variation 25.2 |
Secondary
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.
Time frame: Pre-infusion and post-infusion on Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28) of Tremelimumab | 270 day*mcg/mL | Geometric Coefficient of Variation 58.1 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: AUC (0-28) of Tremelimumab | 228 day*mcg/mL | Geometric Coefficient of Variation 12.4 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax/D of Durvalumab | 20.2 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 27.7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax/D of Durvalumab | 19.8 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 14.2 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax/D of Tremelimumab | 29.2 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 86 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax/D of Tremelimumab | 23.2 (mcg/mL)/(mg/kg) | Geometric Coefficient of Variation 18.8 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax of Durvalumab | 606 mcg/mL | Geometric Coefficient of Variation 27.7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax of Durvalumab | 595 mcg/mL | Geometric Coefficient of Variation 14.2 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax of Tremelimumab | 29.2 mcg/mL | Geometric Coefficient of Variation 86 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmax of Tremelimumab | 23.2 mcg/mL | Geometric Coefficient of Variation 18.8 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmin of Durvalumab | 108 mcg/mL | Geometric Coefficient of Variation 29.6 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmin of Durvalumab | 78.3 mcg/mL | Geometric Coefficient of Variation 94.1 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmin of Tremelimumab | 3.91 mcg/mL | Geometric Coefficient of Variation 41.7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Cmin of Tremelimumab | 3.40 mcg/mL | Geometric Coefficient of Variation 66.2 |
Secondary
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.
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
Population: The ADA analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom baseline, and any post-dose data were available were included in the ADA analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Tremelimumab, Transiently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Durvalumab, Transiently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Tremelimumab, ADA positive at any visit | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Durvalumab, ADA positive at any visit | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Tremelimumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Durvalumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Tremelimumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Durvalumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Durvalumab, ADA positive at any visit | 20 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Durvalumab, Transiently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Tremelimumab, ADA positive at any visit | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Percentage of Participants Who Developed Detectable ADAs | Tremelimumab, Transiently positive | 0 percentage of participants |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: T½λz of Durvalumab | 17.4 days | Geometric Coefficient of Variation 26.2 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: T½λz of Durvalumab | 14.2 days | Geometric Coefficient of Variation 48.6 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: T½λz of Tremelimumab | 15.9 days | Geometric Coefficient of Variation 26.2 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: T½λz of Tremelimumab | 15.6 days | Geometric Coefficient of Variation 40.4 |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Tmax of Durvalumab | 0.049 days |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Tmax of Durvalumab | 0.051 days |
Secondary
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.
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
Population: The PK analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom any post-dose data were available who did not violate or deviate from the CSP in ways that would significantly affect the PK analysis. Only data from the participants analyzed were reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Tmax of Tremelimumab | 0.049 days |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Expansion Phase: Tmax of Tremelimumab | 0.052 days |
Secondary
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.
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
Population: The ADA analysis set included all participants who received at least 1 dose of study treatment per the CSP for whom baseline, and any post-dose data were available were included in the ADA analysis set. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Transiently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, ADA positive at any visit | 25 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Transiently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, ADA positive at any visit | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, ADA positive at any visit | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Transiently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, ADA positive at any visit | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Persistently positive | 0 percentage of participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Transiently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Transiently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Persistently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Transiently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, ADA positive at any visit | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, ADA positive at any visit | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Persistently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Transiently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, Persistently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, ADA positive at any visit | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Persistently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Durvalumab, Transiently positive | 0 percentage of participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Dose-Finding Phase: Percentage of Participants Who Developed Detectable Anti-Drug Antibodies (ADAs) | Tremelimumab, ADA positive at any visit | 0 percentage of participants |
Secondary
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.
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)
Population: Participants who received the Durvalumab + tremelimumab combination who had a pre-treatment sample collected on Day 1 and a repeat sample on Day 8 were included. As the weight of the participant was not believed to impact the immune response, it was determined that aggregating the data by dosing regimen rather than by weight group, was considered acceptable for this particular analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C1D8 | 112.8 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C1D8 | 20.0 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C2D1 | -20.0 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C1D8 | -30.1 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C2D1 | 10.3 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C1D8 | -12.5 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C2D1 | 10.1 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C1D8 | -23.3 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C2D1 | 3.6 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C1D8 | -29.2 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C2D1 | 6.2 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C2D1 | -25.8 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C2D1 | 40.4 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C2D8 | 30.1 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C3D1 | -8.3 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C2D1 | 27.2 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C3D1 | -2.5 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C2D8 | 7.4 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C3D1 | 25.9 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C2D1 | 31.0 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C2D1 | 16.7 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C2D8 | 66.7 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C3D1 | 0.0 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C2D8 | 20.6 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C2D8 | 153.1 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C3D1 | -33.4 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C2D1 | 6.1 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C2D8 | 12.8 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C2D1 | 133.3 percentage of cells per cubic millimeter |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C3D1 | -12.3 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C2D1 | -25.8 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C2D1 | 10.6 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C2D1 | -62.1 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C2D8 | 13.8 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C2D8 | 16.1 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+; C3D1 | 0.6 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C2D8 | -40.0 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C2D1 | -12.0 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C3D1 | 21.9 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C3D1 | 15.7 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C3D1 | 23.0 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C2D1 | 32.2 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD8+ Ki67; C3D1 | -55.4 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C2D8 | 47.4 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | B cells; C2D8 | -8.2 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | NK cells; C3D1 | 43.7 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+; C2D1 | 9.2 percentage of cells per cubic millimeter |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Median Percent Change From Baseline of Cluster of Differentiation 4+ (CD4+), CD8+, B Cells, Natural Killer (NK) Cells, and T-cell Activation With Ki67 | T cells CD4+ Ki67; C2D8 | 118.2 percentage of cells per cubic millimeter |
Secondary
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.
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)
Population: Participants who has a baseline titer collected and who has subsequent samples following a routine childhood immunization were included. As no participants received a routine immunization during the study, no additional samples were collected, hence no data analysed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Number of Participants With Individual Antibody Titer Measurement | 0 Participants |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Number of Participants With Individual Antibody Titer Measurement | 0 Participants |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Number of Participants With Individual Antibody Titer Measurement | 0 Participants |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Number of Participants With Individual Antibody Titer Measurement | 0 Participants |
| SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Number of Participants With Individual Antibody Titer Measurement | 0 Participants |
| STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Number of Participants With Individual Antibody Titer Measurement | 0 Participants |