This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Durvalumab and Tremelimumab for Pediatric Malignancies (NCT03837899), a non-randomized phase 1, phase 2 study. The primary outcome is Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03837899 |
| Phase | Phase 1, Phase 2 |
| Condition | Pediatric Cancer, Solid Tumor Pediatric, Hematological Malignancies |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns pediatric patients with advanced solid tumors and hematological malignancies. The listed conditions include Pediatric Cancer, Solid Tumor Pediatric, and Hematological Malignancies. The primary pharmacokinetic analysis set is defined as participants who received at least one dose and had post-dose data, subject to protocol-related exclusions that could significantly affect the pharmacokinetic analysis.
Intervention
The listed intervention is durvalumab combined with tremelimumab. In the dose-finding description, both drugs are given as intravenous infusions every 4 weeks, with dosing initially at dose level 1 and escalation informed by pharmacokinetic modeling and tolerance. The study objective describes determining a recommended dose and then evaluating the drugs in a dose-expansion phase.
Comparator
There is no randomized control group. The record identifies a non-randomized, single-group model and describes dose groups and disease cohorts. Those groups do not constitute a like-for-like randomized comparison, so differences across them cannot be interpreted as unbiased treatment effects.
Primary question
The registered primary outcome is the maximum serum concentration, or Cmax, of durvalumab during the dose-finding phase. It is a pharmacokinetic measure of drug exposure, not a clinical response endpoint. The record describes measurements at specified points during treatment, but a numerical primary-outcome result is not reported in the registry record.
3. Trial Design
NCT03837899 is a Phase I/II, open-label study sponsored by AstraZeneca. The registry lists an enrollment of 50 and a non-randomized allocation with a single-group model. The study status is active, not recruiting. Its start date is 2019-03-07, and the listed primary completion date is 2023-02-28. These registry entries describe the study record; they do not establish how many participants were ultimately treated or followed.
The stated purpose is to determine a recommended dose of durvalumab and tremelimumab in pediatric patients with advanced solid and hematological cancers, followed by a dose-expansion phase to assess the drugs at the selected dose. The intervention description specifies combination treatment. In dose finding, the drugs are initially administered at dose level 1, with dose escalation based on pharmacokinetic modeling and tolerance. Both drugs are described as intravenous infusions every 4 weeks.
Arm descriptions distinguish participants by weight and dose, and also identify sarcoma and STO groups. The record lists durvalumab doses of 20 mg/kg or 30 mg/kg, each combined with tremelimumab 1mg/kg. Because allocation is non-randomized and the registry explicitly cautions that the arms are not a like-for-like control comparison, observed differences among these groups should not be treated as randomized treatment contrasts. No masking is used, so the study is open-label.
The primary registered outcome is a pharmacokinetic measure rather than a tumor-response or survival endpoint. The record also lists pharmacokinetic outcomes for dose expansion and 48 outcome measures overall. A detailed statistical analysis plan, including any protocol-defined comparisons, is not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 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.
Overall Study
| Stage | Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg |
|---|---|---|---|---|---|---|
| STARTED | 7 | 11 | 3 | 8 | 11 | 10 |
| COMPLETED | 1 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 11 | 3 | 8 | 11 | 10 |
Reasons for not completing this period:
| Reason | Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg |
|---|---|---|---|---|---|---|
| Death | 6 | 8 | 3 | 7 | 8 | 7 |
| Moved to post-trial access program | 0 | 1 | 0 | 0 | 0 | 0 |
| Other | 0 | 0 | 0 | 0 | 0 | 2 |
| Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Study specific discontinuation criteria | 0 | 1 | 0 | 0 | 3 | 1 |
Analysis population for the primary outcome, as defined in the registry: 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.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: The Full analysis set (FAS) included all participants who were assigned to treatment and received at least 1 dose of study treatment.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg |
|---|---|---|---|---|---|---|---|
| Participants analysed | 7 | 11 | 3 | 8 | 11 | 10 | |
| Age, Customized: In utero | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Customized: Preterm newborn infants (gestational age < 37 weeks) | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Customized: Newborns (0-27 days) | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Customized: Infants and toddlers (28 days-23 months) | Participants | 1 | 0 | 0 | 0 | 0 | 0 |
| Age, Customized: Children (2-11 years) | Participants | 0 | 5 | 3 | 6 | 7 | 3 |
| Age, Customized: Adolescents (12-17 years) | Participants | 6 | 6 | 0 | 2 | 4 | 7 |
| Age, Customized: Adults (18-64 years) | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Customized: From 65-84 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 3 | 8 | 1 | 3 | 6 | 5 |
| Sex: Female, Male: Male | Participants | 4 | 3 | 2 | 5 | 5 | 5 |
| Race/Ethnicity, Customized: Black or African American | Participants | 1 | 1 | 0 | 1 | 0 | 0 |
| Race/Ethnicity, Customized: Native Hawaiian or other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 1 | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: White | Participants | 5 | 8 | 2 | 4 | 8 | 6 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 1 | 1 | 3 | 1 | 3 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 1 | 2 | 1 | 1 | 0 | 2 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 6 | 9 | 2 | 7 | 11 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Dose-Finding Phase: Maximum Serum Concentration (Cmax) of Durvalumab, measured over 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.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | micrograms/ milliliter (mcg/mL) |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the maximum serum concentration of durvalumab, called Cmax, during the dose-finding phase. It is expressed in micrograms/ milliliter (mcg/mL), summarized as a geometric mean, with geometric coefficient of variation as the dispersion measure. Serum samples are collected at specified pre-infusion and post-infusion timepoints, from Cycle 1 Day 1 through later cycles, including Cycle 12. The record says Cmax is determined using standard non-compartmental methods.
In general, Cmax describes the highest measured concentration of a drug in serum over the sampling schedule. It is useful in pharmacokinetic work because concentration measurements can help characterize drug exposure and inform dose selection. The geometric mean is a summary suited to positive measurements that may vary multiplicatively; the geometric coefficient of variation expresses relative variability around that summary. These statistical summaries describe concentration data, not direct clinical benefit.
The record does not report a numerical Cmax estimate, its geometric coefficient of variation, or a confidence interval. It therefore does not permit readers to assess the observed concentration level or its precision from the registry information. The listed endpoint should not be mistaken for a measure of tumor response, symptom change, or survival.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies Cmax of durvalumab as the primary dose-finding outcome and describes its measurement schedule and summary statistics. It does not report a numerical Cmax result. Without an estimate and an indication of its uncertainty, the posted information cannot show the observed concentration level or how precisely it was estimated. Nor does the primary endpoint itself answer whether tumors changed or how participants fared clinically.
The study is non-randomized, open-label, and described as a single-group study. The registry lists multiple dose and disease groups, but they are not randomized controls. In general, comparisons among non-randomized groups may reflect differences in participant characteristics, dose assignment, disease type, treatment exposure, or other factors as well as any treatment-related differences. The registry specifically notes that the arms are not a like-for-like control comparison. This limits causal interpretation of any differences between groups.
The study’s stated sequence is dose finding followed by dose expansion. The record says dose escalation is informed by pharmacokinetic modeling and tolerance, but it does not give the detailed escalation algorithm or the rule used to select the recommended dose. The registry record also does not report the dose ultimately recommended. Consequently, the available description explains the intended purpose but does not establish the outcome of dose selection.
Safety entries are reported across dose or disease groups, including counts of participants at risk and affected for serious and other adverse events, and deaths. These are descriptive group-level counts. They do not by themselves establish that the study drugs caused an event, and the varying groups are not a randomized basis for comparing risk. The listed serious-event terms have percentages, but the registry information does not provide a denominator definition alongside those terms.
Planning illustrations based on an observed effect, if consulted, should be read as hypothetical design calculations under stated assumptions, not as observed power or evidence that a future study would reproduce the effect. The registry record does not report the effect estimate underlying such illustrations as a primary Cmax result. Overall, the available information describes the design, endpoint, and some safety reporting, but not a numerical primary outcome or an efficacy conclusion.
9. Statistical Methods Explained
The primary outcome is a pharmacokinetic endpoint. In general, pharmacokinetics describes how drug concentrations change in the body over time. The registered endpoint, Cmax, is the maximum serum concentration of durvalumab measured according to a specified sampling schedule. The record states that serum samples are obtained before and after infusion at designated cycle timepoints, and that Cmax is determined using standard non-compartmental methods. This describes the endpoint’s measurement approach; the detailed calculation procedures are not reported in the registry record.
Why use a geometric mean?
The primary summary is a geometric mean. In general, this is calculated on a logarithmic scale and then expressed on the original scale. It can be appropriate for positive concentration measurements when values vary proportionally rather than by a constant additive amount. It is not the same as an arithmetic average, and it should be interpreted alongside the variability measure and, where available, an interval estimate. A numerical geometric mean and confidence interval for the primary endpoint are not reported in the registry record.
What does the dispersion measure describe?
The registered dispersion measure is the geometric coefficient of variation. In general, a coefficient of variation describes variability relative to the scale of the measurements. The geometric version is commonly paired with geometric summaries when data are analyzed on a log scale. It helps convey how much concentration measurements vary proportionally, but it is not a confidence interval and does not by itself indicate the precision of the estimated geometric mean. The registry does not report a numerical value for this measure for the primary endpoint.
How does dose finding fit the design?
The record describes dose finding in which participants initially receive dose level 1 and doses are escalated based on pharmacokinetic modeling and tolerance. This is a description of the intended approach, not a full statistical rule. The precise escalation boundaries, cohort decision criteria, stopping rules, or dose-selection procedure are not reported in the registry record. The listed dose groups include durvalumab at 20 mg/kg or 30 mg/kg with tremelimumab 1mg/kg; the record also separates groups by weight or disease category. Since allocation is non-randomized, comparisons between those groups are descriptive and potentially affected by group differences.
The protocol’s dose-finding objective is to determine a recommended dose, after which the study description says a dose-expansion phase will test efficacy. The registry’s primary endpoint remains a pharmacokinetic measure. A pharmacokinetic result can inform exposure and dose selection, but it does not substitute for a clinical endpoint. The efficacy outcomes, response definitions, and their analysis details are not reported in the registry record as described in the registry entries.
What does non-compartmental analysis mean?
In general, non-compartmental analysis uses observed concentration-time data to derive pharmacokinetic measures without requiring a prespecified model of body compartments. The record states that this approach is used to determine Cmax. It does not supply the underlying concentration data, the handling of values below quantification limits, or detailed implementation choices. Those details matter because sampling patterns and data handling can affect estimated pharmacokinetic summaries.
The dose-expansion secondary outcomes include durvalumab Cmax, Cmin, AUC (0-14), AUC (0-28), Tmax, T½λz, AUC (0-14)/D, and AUC (0-28)/D. In general, Cmin is a low or trough concentration measure; AUC represents concentration accumulated over a time interval; Tmax is the time to the maximum concentration; and T½λz describes a terminal half-life measure. Dose-normalized AUC expresses exposure relative to dose. These terms characterize drug exposure, not clinical efficacy. Numerical estimates for these secondary outcomes are not reported in the registry record.
The record defines the pharmacokinetic analysis set as participants who received at least 1 dose, had any post-dose data available, and did not have a protocol violation or deviation expected to significantly affect the pharmacokinetic analysis. This is a specified analysis-population definition. The number included in that set and the effects of exclusions or missing samples are not reported in the registry record.
General interpretation of uncertainty relies on confidence intervals and appropriate models, but no primary endpoint interval, hypothesis test, or model-based treatment contrast is reported in the registry record. The record lists 48 outcome measures and 0 analyses. Those entries do not establish that all outcomes were measured or analyzed in the same population, and details of analysis methods beyond the stated Cmax approach are not reported. Any planning illustration based on an observed effect is a design calculation under its assumptions, not observed power and not evidence of a treatment effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 48 outcome measures and 0 analyses. It does not report a multiplicity strategy for handling inference across outcomes, dose groups, timepoints, or phases. In general, when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase; prespecified testing procedures can help control that risk. Without a reported plan, the inferential status of any individual result cannot be assessed from the registry record. No numerical hypothesis tests for the primary endpoint are reported.
The primary pharmacokinetic analysis set is described: eligible participants received at least 1 dose, had post-dose data, and had no protocol violation or deviation judged likely to significantly affect the pharmacokinetic analysis. This does not specify how missing concentration measurements are handled, how partial sampling schedules are treated, or whether sensitivity analyses are planned. Those details are not reported in the registry record. The number of participants contributing to the primary endpoint is also not reported in the registry record.
The registry does not report a detailed statistical analysis plan, the handling of missing clinical outcomes, or methods for any efficacy analyses. It also does not report whether interim analyses were planned. These omissions prevent evaluation of how analysis choices may have affected endpoint estimates or interpretation.
The sample-size assumptions describe planning illustrations computed from an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not the study’s own design justification or observed power. The protocol’s sample-size justification is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 1 | 7 | 14.3% |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 1 | 11 | 9.1% |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 0 | 3 | 0.0% |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 1 | 8 | 12.5% |
| SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 6 | 11 | 54.5% |
| STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 3 | 10 | 30.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 6 of 7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 8 of 11 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 3 of 3 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 7 of 8 |
| SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 8 of 11 |
| STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 7 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 6 of 7 |
| Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 11 of 11 |
| Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | 3 of 3 |
| Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 7 of 8 |
| SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 8 of 11 |
| STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | 9 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 7 | 0 of 11 | 0 of 3 | 0 of 8 | 3 of 11 | 0 of 10 |
| Transverse sinus thrombosis | Nervous system disorders | 0 of 7 | 0 of 11 | 0 of 3 | 1 of 8 | 0 of 11 | 0 of 10 |
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | 0 of 7 | 0 of 11 | 0 of 3 | 0 of 8 | 1 of 11 | 0 of 10 |
| Abdominal pain | Gastrointestinal disorders | 0 of 7 | 0 of 11 | 0 of 3 | 0 of 8 | 1 of 11 | 0 of 10 |
| Pulmonary thrombosis | Respiratory, thoracic and mediastinal disorders | 0 of 7 | 0 of 11 | 0 of 3 | 0 of 8 | 0 of 11 | 1 of 10 |
| Ascites | Gastrointestinal disorders | 0 of 7 | 0 of 11 | 0 of 3 | 0 of 8 | 1 of 11 | 0 of 10 |
| Colitis | Gastrointestinal disorders | 0 of 7 | 1 of 11 | 0 of 3 | 0 of 8 | 0 of 11 | 0 of 10 |
| Constipation | Gastrointestinal disorders | 0 of 7 | 0 of 11 | 0 of 3 | 0 of 8 | 0 of 11 | 1 of 10 |
| Diarrhoea | Gastrointestinal disorders | 0 of 7 | 1 of 11 | 0 of 3 | 0 of 8 | 0 of 11 | 0 of 10 |
| Anaemia | Blood and lymphatic system disorders | 1 of 7 | 0 of 11 | 0 of 3 | 0 of 8 | 0 of 11 | 0 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A (>= 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm A (>= 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 20 mg/kg + Tremelimumab 1mg/kg | Arm B (< 35 kg): Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | SARCOMA: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg | STO: Durvalumab 30 mg/kg + Tremelimumab 1mg/kg |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 2 of 7 | 1 of 11 | 0 of 3 | 2 of 8 | 6 of 11 | 4 of 10 |
| Anaemia | Blood and lymphatic system disorders | 2 of 7 | 2 of 11 | 1 of 3 | 1 of 8 | 4 of 11 | 3 of 10 |
| Vomiting | Gastrointestinal disorders | 3 of 7 | 2 of 11 | 0 of 3 | 3 of 8 | 2 of 11 | 2 of 10 |
| Headache | Nervous system disorders | 1 of 7 | 4 of 11 | 0 of 3 | 2 of 8 | 1 of 11 | 2 of 10 |
| Abdominal pain | Gastrointestinal disorders | 0 of 7 | 3 of 11 | 0 of 3 | 1 of 8 | 3 of 11 | 1 of 10 |
| Diarrhoea | Gastrointestinal disorders | 0 of 7 | 3 of 11 | 1 of 3 | 0 of 8 | 2 of 11 | 2 of 10 |
| Nausea | Gastrointestinal disorders | 0 of 7 | 7 of 11 | 0 of 3 | 0 of 8 | 0 of 11 | 1 of 10 |
| Alanine aminotransferase increased | Investigations | 0 of 7 | 4 of 11 | 1 of 3 | 1 of 8 | 2 of 11 | 0 of 10 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 7 | 1 of 11 | 0 of 3 | 2 of 8 | 0 of 11 | 3 of 10 |
| Asthenia | General disorders | 1 of 7 | 2 of 11 | 0 of 3 | 0 of 8 | 2 of 11 | 2 of 10 |
Serious events with the highest arm-level rate: pyrexia (27.3%), anaemia (14.3%), transverse sinus thrombosis (12.5%), pulmonary thrombosis (10.0%), constipation (10.0%).
The registry reports safety counts by listed dose or disease group. For each group it gives participants at risk and affected for serious adverse events, participants at risk and affected for other adverse events, and deaths. These should be read within the reported group rather than combined across groups. The record does not provide a common randomized control group, and the groups are not a like-for-like comparison. Differences in counts therefore cannot be interpreted as comparative treatment effects.
The listed serious adverse event terms include Pyrexia at 27.3%, Anaemia at 14.3%, Transverse sinus thrombosis at 12.5%, Pulmonary thrombosis at 10.0%, Constipation at 10.0%, and Platelet count decreased at 10.0%. The registry information does not define the denominator for these percentages alongside the term list, so they should not be converted into participant counts or compared directly with group-level counts.
In general, adverse-event summaries describe events recorded during a study period; they do not establish causation. The record does not report event timing, severity grades, exposure-adjusted rates, or attribution details in the registry record described. Death counts are reported by group, but their causes and relationship to treatment are not reported in the registry record. The listed safety data are descriptive and should be interpreted with these limits.
12. What the Result Does, and Does Not, Mean
The study record describes a Phase I/II investigation intended to select a dose of durvalumab and tremelimumab and then evaluate the drugs in a dose-expansion phase. The registered primary outcome is durvalumab Cmax, a pharmacokinetic measure. That focus is appropriate to a dose-finding question: concentration data can characterize exposure and contribute to dose selection. It does not directly measure tumor response, survival, or quality of life.
The available record does not report a numerical primary Cmax result or its uncertainty. It also does not state the recommended dose reached, or provide a numerical efficacy result. Therefore, the information cannot establish the magnitude or precision of the primary pharmacokinetic outcome, nor can it support a conclusion about clinical benefit. This is an absence of reported results in the registry record, not evidence that an outcome was zero or that an analysis found no effect.
The study is non-randomized and open-label. Its dose and disease groups are not randomized controls, so differences across those groups cannot isolate the effect of treatment from other differences between participants or groups. The registry explicitly warns that the arms are not a like-for-like control comparison. Any descriptive safety figures likewise do not demonstrate that a particular event was caused by the study drugs.
The safety entries show reported counts by group and percentages for selected serious-event terms. They do not provide, in the registry record described, a complete account of event timing, attribution, or exposure-adjusted risk. The record also does not report the details needed to assess missingness, multiplicity, or the full statistical analysis plan.
In general, a trial’s design and posted outcomes answer different questions: design describes what investigators intended to evaluate, while results are needed to assess observed estimates and their precision. Here, the registry information supports a description of the study’s aims, structure, endpoint, and selected safety reporting. It does not support a conclusion that the combination is effective or ineffective.
13. Why This Trial Matters Statistically
This study is statistically notable because its primary question is about pharmacokinetics and dose selection in a pediatric population with advanced cancers. Cmax and other listed concentration measures describe exposure to durvalumab. In general, these measures can help characterize how drug concentrations behave under a dosing schedule and can contribute to decisions about dose levels. They answer a different question from whether a treatment changes a clinical outcome.
The dose-finding and dose-expansion structure also matters for interpretation. A dose selected using exposure and tolerance information may then be studied further, but evidence from a dose-finding phase should not automatically be treated as evidence of efficacy. The registry description states this sequence of objectives without reporting a numerical recommended dose or primary Cmax result.
The non-randomized design places limits on comparisons between the listed groups. This is especially important because groups are defined by dose, weight, or cancer type, rather than randomized assignment to comparable conditions. General statistical methods cannot remove all potential differences between groups when allocation is not randomized, particularly when the record does not report adjustment methods or a detailed analysis plan.
Finally, the endpoint’s summary needs its variability and uncertainty to be interpretable. The registry specifies a geometric mean and geometric coefficient of variation, but does not report numerical values for the primary outcome. The record therefore defines what was intended to be measured more clearly than it documents what was observed. Distinguishing endpoint definition, study design, and actual results is central to statistical reading of this trial.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry information describes the study as active but not recruiting and lists a primary completion date of 2023-02-28; it does not establish the timing or completeness of posted results. Enrollment is listed as 50, but the number treated, the number included in the pharmacokinetic analysis set, and the number completing relevant assessments are not reported in the registry record.
The primary endpoint is defined, but its numerical estimate and uncertainty are not reported. The record also does not specify the recommended dose selected, the detailed dose-escalation criteria, or the precise analysis procedures beyond use of standard non-compartmental methods for Cmax. Concentration data and handling rules for incomplete or missing samples are not reported.
The non-randomized, open-label design means that the listed groups are not suitable as randomized controls. Group membership differs by dose, weight category, or disease category, and the record does not report adjusted analyses that would address such differences. Efficacy outcomes and their numerical results are not included in the registry record described. The registry lists pharmacokinetic secondary outcomes, but not their numerical findings.
Safety reporting is also limited for interpretation: the record gives group-level counts and selected serious-event percentages, but the denominator definition for the percentages, event attribution, timing, severity grading, and exposure-adjusted comparisons are not reported in the registry record. A detailed statistical analysis plan, multiplicity strategy, missing-data approach, interim-analysis plan, and sample-size justification are not reported. These limits mean the record supports a description of the study design and recorded safety summaries, but not a comprehensive assessment of treatment effects or their precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Durvalumab and Tremelimumab for Pediatric Malignancies — NCT03837899.
- Registry record last updated 2026-09-29; status last verified 2026-09.
- Results first posted 2024-03-19.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT03837899 is a Phase I/II, open-label, non-randomized study sponsored by AstraZeneca, with a single-group model and listed enrollment of 50. The registry status is active, not recruiting. The study concerns durvalumab and tremelimumab in pediatric patients with advanced solid tumors and hematological malignancies, with dose finding followed by dose expansion described as the study objective.
The primary outcome is dose-finding Cmax of durvalumab, summarized by geometric mean and geometric coefficient of variation. The record describes serum sampling and standard non-compartmental methods, but a numerical primary result is not reported in the registry record. Safety counts are listed by dose or disease group; the arms are not a like-for-like control comparison. Detailed analysis, missing-data, and multiplicity methods are not reported in the registry record.