Study of Tremelimumab in Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Tremelimumab in Patients With Advanced Solid Tumors (NCT02527434), a na phase 2 study. The primary outcome is Percentage of Patients With Confirmed Overall Response During Tremelimumab Monotherapy Phase.

2. Clinical Question

This question concerns the proportion of patients meeting a defined tumor-response criterion during the initial treatment phase. Confirmation is part of the endpoint definition: a response was not counted merely because an assessment first suggested complete or partial response. The registry record specifies that the primary measure was based on treated patients with measurable disease at baseline.

The study also lists outcomes for response duration, disease control, progression-free survival, overall survival, best objective response, and response during retreatment. Those measures address different aspects of disease course and treatment sequence. The primary question is narrower: it asks whether a confirmed response was observed during the initial tremelimumab monotherapy phase. The response estimate, its confidence interval limits, and the number of patients contributing to that primary endpoint are not reported in the registry record. Without those results, the response proportion itself cannot be described or assessed for precision.

3. Trial Design

This was a Phase II, multicenter, open-label, single-group study of tremelimumab monotherapy in patients with advanced solid tumors. The conditions named in the registry record were urothelial bladder cancer, triple-negative breast cancer, and pancreatic ductal adenocarcinoma. Planned enrollment was 64. The study is listed as completed; its recorded start was 2015-11-02 and its primary completion was 2018-02-17.

Allocation is recorded as NA, and masking as none. These design features mean the registry record does not describe randomized assignment or blinded treatment assessment. The primary endpoint was assessed by the site investigator. The record describes an initial tremelimumab monotherapy phase, with an option for eligible patients to receive MEDI4736 monotherapy or MEDI4736 plus tremelimumab after progressive disease. Thus, the treatment path could continue beyond the initial phase for eligible patients; the primary response question remains specific to tremelimumab monotherapy.

The listed interventions include tremelimumab monotherapy, MEDI4736 monotherapy, and MEDI4736 plus tremelimumab combination therapy. Safety groups are also listed for monotherapy, combination therapy, and MEDI4736 monotherapy, separated by cancer type. Those groups describe treatment-specific records, but do not establish randomized comparisons between treatments. The registry record does not report how eligibility for sequencing was determined, how many patients entered each later treatment phase, or how the treatment groups were formed beyond the stated sequence option.

A single-group design can describe outcomes observed among participants receiving the study treatment, but it does not create a concurrent control contrast. Differences between the cancer-specific groups or treatment phases cannot be interpreted as randomized treatment effects. The detailed protocol, including any further design rationale, 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: The patients were split into 3 different analysis cohorts based on their tumor types: urothelial bladder cancer (UBC), triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

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: Analysis was performed on the FAS (all treated patients who received at least 1 dose of tremelimumab monotherapy).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients With Confirmed Overall Response During Tremelimumab Monotherapy Phase, measured over From baseline to 12 months in the tremelimumab monotherapy phase.

The primary endpoint is the percentage of patients with a confirmed overall response during the tremelimumab monotherapy phase. Overall response was defined as complete response or partial response, assessed by the site investigator using RECIST 1.1. The timeframe was from baseline to 12 months in that phase. The analysis description identifies treated patients with measurable disease at baseline, while the analysis population is described as all treated patients who received at least one dose of tremelimumab monotherapy.

This is a binary endpoint at the participant level: a patient either meets the confirmed-response definition or does not. Expressing the result as a percentage provides a direct summary of how often the specified response criterion was met in the assessed population. Confirmation is intended to distinguish a response that is sustained according to the endpoint rules from an initial assessment that may not be confirmed.

Response rate is distinct from response duration, disease control, progression-free survival, and overall survival. A response proportion alone does not describe how long responses lasted or how long patients remained alive or free of progression. Those outcomes are separately listed as secondary measures. The registry record specifies a Clopper-Pearson method for the 95% confidence interval, but the primary response percentage and confidence interval are not reported in the registry record. Therefore, the endpoint definition is available, while its observed result and precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a response percentage represent?

For a binary endpoint, each participant is classified according to whether the endpoint definition was met. The response percentage summarizes the share of the analysis population classified as responders. In this study, the definition required confirmed complete response or partial response under RECIST 1.1, as assessed by the site investigator during the tremelimumab monotherapy phase.

The percentage is a descriptive estimate for the participants included in that analysis. It is not, by itself, a comparison with what would have happened under another treatment. In a single-group study, an observed response proportion characterizes the study group; it does not supply a randomized estimate of a difference between treatments. The registry record does not report the response count or percentage, so no numerical response estimate can be interpreted.

How should the confidence interval be understood?

The record specifies a 95% confidence interval calculated by the Clopper-Pearson method. In general, a confidence interval expresses uncertainty around an estimate using a method with stated long-run coverage properties when its assumptions hold. It is not a guarantee that the particular interval contains the true value, nor is it a probability statement about the true response rate after the data have been observed.

Clopper-Pearson is an exact interval method for a binomial proportion. It is designed for a setting where each participant contributes a response or nonresponse classification. The interval's limits are not reported in the registry record. Without the response count and interval limits, readers cannot assess whether the estimate is relatively precise or uncertain.

Why does the analysis population matter?

The primary description refers to all treated patients who had measurable disease at baseline, while the population description defines the FAS as all treated patients who received at least one dose of tremelimumab monotherapy. These descriptions identify treatment exposure and baseline measurability as relevant to the analysis. The registry record does not report the number of patients in either described population or explain how any difference between the wording was handled in the endpoint calculation.

General statistical principle: defining the analysis population before examining outcomes helps make clear who contributes to an estimate. Excluding people without measurable baseline disease may be appropriate to an endpoint that requires measurable disease, but how exclusions and unevaluable assessments were handled should be explicit. The registry record does not report those handling details or the count excluded from the primary analysis.

What can the study design estimate?

The study is listed as single group, open label, with allocation NA and no masking. General statistical principle: a single-group study can estimate an outcome proportion among observed participants, but it cannot directly estimate a randomized between-group treatment contrast. Randomization helps balance measured and unmeasured prognostic factors across assigned groups; that protection is not described for this study. Open-label design means treatment assignment was not masked, and the endpoint assessment was performed by the site investigator.

The response criteria provide a defined basis for classifying outcomes, but criteria alone do not create blinding or a control group. The registry record does not report any independent central review or other assessment process, so none should be assumed. The primary result, even if available, would need interpretation as a response proportion in the enrolled study population rather than as a direct causal comparison.

How does sequencing affect interpretation?

Eligible patients could be sequenced to MEDI4736 monotherapy or the combination of MEDI4736 and tremelimumab after progressive disease. The primary endpoint, however, is explicitly tied to the initial tremelimumab monotherapy phase. Outcomes collected during a later phase concern a different treatment period and have separate listed measures for response and response duration. They should not be treated as interchangeable with the primary endpoint.

General statistical principle: later-phase outcomes can be affected by who remains eligible, who chooses or receives further treatment, and the timing of treatment transitions. Such selection can make later groups differ from the initial study population. The registry record does not report transition counts, detailed eligibility rules, or analyses that adjust for this selection. It also does not report a comparative analysis of the treatment sequences.

What does the sample-size planning information mean?

The stated sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The planning values are not reported in the registry record presented for this study, and the listed assumptions are not evidence that the trial itself used that design. In particular, the actual study is recorded as single group, not a two-arm randomized comparison.

Such planning illustrations address the number of participants per arm that would be needed under specified assumptions for a target power. They are not observed power and do not establish that a study was adequately powered for its actual design. Because the primary response estimate is not reported, the observed effect underlying any such illustration cannot be examined from the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("UBC - Tremelimumab Monotherapy", "TNBC - Tremelimumab Monotherapy", "PDAC - Tremelimumab Monotherapy")
n      <- c(32, 12, 20)
events <- c(6, 1, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  UBC - Tremelimumab Monotherapy  32  6  18.8  7.2  36.4  8.9  35.3  9.0  35.5
ARM  TNBC - Tremelimumab Monotherapy  12  1  8.3  0.2  38.5  1.5  35.4  1.9  36.0
ARM  PDAC - Tremelimumab Monotherapy  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures, including the primary confirmed-response measure and secondary measures for response duration, disease control, progression-free survival, best objective response, overall survival, and outcomes during retreatment. When multiple outcomes are examined, the chance of at least one apparently notable finding can increase if each is tested without accounting for the family of analyses. General statistical practice may use prespecified hierarchies, adjustment procedures, or a clearly descriptive interpretation, depending on the study goals.

The registry record does not report a multiplicity adjustment, testing hierarchy, or other plan for interpreting multiple outcomes. It also lists zero analyses. This listing does not show whether analyses were performed outside what is recorded; it means analysis details are not reported in the registry record. No inference about statistical significance or confirmatory status can be made from the count of listed outcomes alone.

Missing-data handling is not reported in the registry record. In general, response analyses need to specify how participants with missing assessments, insufficient follow-up, or unevaluable response status are treated. Different rules can change the denominator and the resulting estimate. The record defines the analysis population in terms of treatment and baseline measurable disease, but does not describe imputation, censoring, or a rule for unevaluable cases.

The record's primary endpoint description and FAS description both refer to treated patients, with baseline measurability specifically stated for the response assessment. The number included in the primary analysis and the handling of any exclusions are not reported in the registry record. These omissions prevent readers from checking the analysis denominator or assessing how incomplete assessments may have affected the posted result.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (25.0%), diarrhoea (25.0%), large intestinal obstruction (25.0%), jaundice cholestatic (25.0%), encephalopathy (25.0%).

The safety figures are presented by cancer type and treatment group. For tremelimumab monotherapy, serious adverse events affected 18 of 32 participants in the urothelial bladder cancer group, 4 of 12 in the triple-negative breast cancer group, and 11 of 20 in the pancreatic ductal adenocarcinoma group. Other adverse events affected 30 of 32, 10 of 12, and 19 of 20 participants in those respective groups. Reported deaths in those groups were 13, 4, and 12.

For combination therapy, serious adverse events affected 3 of 7 participants with urothelial bladder cancer, 2 of 5 with triple-negative breast cancer, and 3 of 4 with pancreatic ductal adenocarcinoma. Other adverse events affected 7 of 7, 5 of 5, and 4 of 4; reported deaths were 4, 2, and 4. For MEDI4736 monotherapy, serious adverse events affected 1 of 4 participants in the urothelial bladder cancer group and 0 of 1 in the pancreatic ductal adenocarcinoma group; other adverse events affected 4 of 4 and 1 of 1, and reported deaths were 4 and 1.

The listed serious-event terms—anaemia, diarrhoea, large intestinal obstruction, jaundice cholestatic, encephalopathy, and pneumonitis—are each reported at 25.0%. Their denominators and cohort-specific context are not reported in the registry record. The death counts do not establish cause or treatment attribution. Group sizes vary, and the groups are not randomized comparisons; these counts should be read descriptively rather than as comparative safety estimates.

13. What the Result Does, and Does Not, Mean

The registry record establishes how the primary response outcome was defined and how it was intended to be summarized. It describes confirmed complete or partial response under RECIST 1.1, assessed by the site investigator during the initial tremelimumab monotherapy phase. It also specifies the Clopper-Pearson method for the 95% confidence interval. These details help readers understand what the endpoint means and what method was planned for its uncertainty interval.

However, the primary response count, percentage, and confidence interval are not reported in the registry record. The posted information therefore does not show how many patients responded, what the observed response proportion was, or how precise that estimate was. The endpoint definition alone is not an outcome result. No claim about the magnitude of response can be supported from the registry record.

Even with a reported response percentage, the single-group design would support a description of outcomes in the study population rather than a randomized comparison with another treatment. The registry record does not describe a concurrent control group. Its open-label design and investigator assessment are also relevant context. A defined response framework supports consistent classification, but does not remove the limitations of an unblinded, nonrandomized design.

The study covered three different cancer types and allowed eligible patients to proceed to later treatment phases after progressive disease. These features matter because participants and treatment periods are not necessarily comparable across groups. The record does not report the numbers entering each later phase or provide detailed analyses by cancer type. Accordingly, neither cross-group comparisons nor conclusions about the later treatment sequence are supported by the information reported.

The appropriate statistical reading is therefore limited: the endpoint and interval method are specified, while the primary result and several analysis details are not reported. Safety counts are descriptive and do not establish treatment causation. Neither the outcome definition nor the safety summaries alone establish a treatment effect.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why an endpoint definition and an outcome estimate are separate parts of evidence. The registry record gives a specific definition for confirmed response, identifies the assessment framework, states the analysis population, and names the confidence-interval method. Those details make the intended estimand more understandable. Yet the response count, percentage, and interval limits are not reported in the registry record, so the outcome cannot be evaluated quantitatively.

The design also illustrates the distinction between estimating an outcome in a treated cohort and estimating a comparative treatment effect. A single-group study can describe what was observed among participants, but without randomized allocation and a comparator it does not directly estimate how outcomes differ under alternative treatments. The open-label design and investigator assessment add interpretive context, while the use of RECIST 1.1 gives a defined response framework.

The three disease groups and the option for later treatment sequencing make the analysis population and treatment period especially important. Initial monotherapy outcomes are not equivalent to later retreatment outcomes, and descriptive safety groups do not constitute like-for-like comparisons. Clear reporting of denominators, transition counts, missing-assessment rules, and results by disease group would help readers understand the scope and precision of each estimate. Those details are not reported in the registry record.

Finally, the registry lists multiple outcomes but does not report a multiplicity strategy or analysis details. This highlights why a prespecified interpretation plan matters when a study tracks several endpoints. The statistical significance or confirmatory status of any result cannot be inferred from the outcome list. Overall, the record offers useful design and endpoint definitions, but its reported information is insufficient to assess the primary response result.

15. 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 most direct limitation for interpreting the primary endpoint is that its observed response count, percentage, confidence interval limits, and analysis denominator are not reported in the registry record. Although the endpoint definition and interval method are stated, the result's magnitude and precision cannot be assessed.

The study is listed as single group, open label, with no masking and allocation recorded as NA. There is no concurrent randomized control described, so the design cannot support a randomized treatment contrast. The primary endpoint was assessed by the site investigator; independent review procedures are not reported in the registry record.

The study includes urothelial bladder cancer, triple-negative breast cancer, and pancreatic ductal adenocarcinoma. The registry record does not report primary response results separately by cancer type. The planned enrollment was 64, but the actual number contributing to the primary response analysis is not reported. Eligibility for sequencing after progressive disease, treatment transitions, and participant counts in later phases are also not reported in the registry record.

Missing-data rules, handling of unevaluable assessments, and the multiplicity strategy are not reported in the registry record. The record lists 12 outcome measures and zero analyses, but this does not indicate whether analyses were performed outside the listed registry information. The safety figures are broken out across small and unequal groups; the record does not establish that these groups are comparable, and reported death counts do not identify cause or treatment attribution.

These limitations constrain interpretation of both efficacy and safety. They do not establish that an outcome was favorable or unfavorable; they identify which conclusions cannot be drawn from the information reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Tremelimumab in Patients With Advanced Solid Tumors — NCT02527434.
• Registry record last updated 2023-11-15; status last verified 2023-10.
• Results first posted 2019-03-05.
• 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.

19. Record Summary

NCT02527434 is a completed Phase II, multicenter, open-label, single-group study sponsored by AstraZeneca. The study concerns tremelimumab monotherapy in patients with advanced urothelial bladder cancer, triple-negative breast cancer, or pancreatic ductal adenocarcinoma. Planned enrollment was 64; the recorded start date was 2015-11-02 and primary completion date was 2018-02-17.

The primary endpoint was the percentage of patients with confirmed complete or partial response during the tremelimumab monotherapy phase, assessed by the site investigator using RECIST 1.1 from baseline to 12 months. The record specifies a Clopper-Pearson 95% confidence interval. Eligible patients could proceed after progressive disease to MEDI4736 monotherapy or MEDI4736 plus tremelimumab.

The primary response count, percentage, and interval limits are not reported in the registry record. The record lists 12 outcome measures and zero analyses. It includes safety counts by cancer type and treatment group, which are descriptive and do not form randomized comparisons.