Testing Whether the Combination of Two Immunotherapy Drugs Have Activity in Recurrent or Persistent Clear Cell Ovarian Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing Whether the Combination of Two Immunotherapy Drugs Have Activity in Recurrent or Persistent Clear Cell Ovarian Cancer (NCT03602586), a na phase 2 study. The primary outcome is Complete or Partial Objective Tumor Response.

2. Clinical Question

This question is about tumor response during a defined period, not a direct comparison of the combination with another treatment. Progression-free survival and overall survival were listed as secondary outcomes, along with adverse events of grade 3 or higher. Their definitions and numerical results are not reported in the registry record. The study is identified as phase II and the listed enrollment is 14. Those details describe the study’s scale and phase, but do not fill in the missing response result or establish how representative the evaluable participants were.

3. Trial Design

This was a phase II, single-group study with no allocation and no masking. The registry lists enrollment of 14 participants and identifies the National Cancer Institute as sponsor. Its status is completed; the recorded study start was 2018-12-21 and primary completion was 2021-02-01. These dates describe the registered study timeline and do not supply details about when individual participants were assessed or followed.

Participants received epacadostat and pembrolizumab as a combination regimen. Epacadostat was taken by mouth twice daily, while pembrolizumab was administered intravenously over 30 minutes every three weeks. The treatment description states that cycles repeated every 21 days in the absence of disease progression or unacceptable toxicity. Other protocol details, including dose amounts, are not reported in the registry record.

The design has no concurrent control arm. Although the brief summary mentions usual treatment options, it does not describe participants assigned to those options. As a result, the study can describe outcomes observed among participants receiving the combination, but the design does not provide a like-for-like comparison against usual treatment. There is also no masking, so the record describes an open-label design.

The primary endpoint was complete or partial objective tumor response within 7 months of study entry, assessed by RECIST version 1.1. Progression-free survival, overall survival, and adverse events of grade 3 or higher were listed as secondary outcomes. The registry record does not report the statistical analysis plan, the approach to follow-up, or the results for these outcomes. It also does not report a sample-size justification or the number of participants included in each outcome analysis.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable patients

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.

6. Primary Endpoint

The registry lists the primary outcome as Complete or Partial Objective Tumor Response, measured over Within 7 months of study entry.

The primary endpoint counts participants with a complete or partial objective tumor response within 7 months of study entry. The registry identifies the assessed population as evaluable patients and names RECIST version 1.1 as the response criteria. It describes complete response as disappearance of all target lesions. Its description of partial response includes a decrease of at least 20% in the sum of the longest diameters of target lesions and a 5 mm absolute increase. That wording combines a decrease and an increase; the registry record does not clarify the apparent ambiguity. It defines overall response as complete response plus partial response.

Objective response is used to describe tumor change under stated criteria and within a stated assessment window. Counting participants rather than reporting only a tumor measurement gives a response count for the defined population. In general, a response endpoint can summarize observed tumor changes, but it does not by itself describe how long a response lasts or whether an outcome differs from what would have occurred under another treatment.

The registry record does not report the observed response count, the evaluable population size, or a response estimate. It says that exact 95% confidence limits accounting for interim analysis will be provided in the final report; those limits are not included in the registry record. The endpoint definition is therefore available, but the posted record does not give the result needed to quantify response frequency or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a binary primary outcome: whether an evaluable participant had a complete or partial objective tumor response within 7 months of study entry. For this kind of outcome, a basic summary can be a count of participants meeting the response definition and the number assessed. The record identifies the outcome unit as participants, but it does not give the response count or the size of the evaluable population. Accordingly, there is no observed response proportion or estimate to interpret from the registry record.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate using the observed data and a specified statistical procedure. A point estimate alone does not show how precisely an outcome has been estimated. With a small study population, uncertainty may be substantial, but the actual interval depends on the observed outcome and the method used. No response estimate or interval is reported in the registry record, so the precision of this study’s primary result cannot be evaluated from the posted information.

The endpoint description states that exact 95% confidence limits, accounting for interim analysis, will be provided in the final report. This records an intended feature of the reporting, not the limits themselves. The timing and number of interim analyses, their statistical procedures, and any effect on the final analysis are not reported in the registry record. It is therefore not possible to reconstruct or assess the intended adjustment from the available information.

Why does the single-group design matter?

A single-group design estimates outcomes among participants who received the study regimen. Without a concurrent control group, there is no randomized contrast within the trial to separate outcomes associated with treatment from other influences. Randomization, when used, helps balance known and unknown participant characteristics between groups on average. This study had no allocation and no masking, so a comparative treatment effect cannot be inferred from an internal randomized comparison. The registry’s mention of usual treatment in the brief summary does not create a control arm.

Open-label means that masking was absent. In general, knowledge of treatment assignment can influence some aspects of care, reporting, or assessment. RECIST criteria provide defined response categories, but the registry record does not describe independent review, assessor masking, or other procedures that might address assessment-related concerns. Those procedures are not reported in the registry record.

How should planning assumptions be read?

General sample-size illustrations are planning exercises, not observed results or evidence that a study had a particular probability of detecting an effect. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of an observed effect. These are assumptions for an illustration, not a description of this single-group trial’s treatment allocation. The registry record does not report a sample-size justification for the trial. The observed effect needed to ground such an illustration is also not reported in the registry record, so the planning assumptions should not be confused with the trial’s own design rationale or with observed power.

In general, over-dispersion means that observed variability is greater than a statistical model expects. Accounting for it can affect uncertainty estimates and, depending on the analysis, standard errors or intervals. That concept does not establish that over-dispersion was present or modeled in this study. The registry record does not report a statistical analysis plan or identify a model for the primary endpoint, so no claim can be made about whether such an adjustment was relevant or used.

What is not available for secondary outcomes?

Progression-free survival and overall survival are listed as secondary outcomes, but definitions, time origins, censoring rules, follow-up details, estimates, and confidence intervals are not reported in the registry record. In general, time-to-event analyses account for the time participants are followed and whether an event has occurred by the end of observation. The method depends on definitions of the event and censoring. Those details are necessary to interpret such analyses and are not available.

Likewise, adverse events of grade 3 or higher are listed as a secondary outcome, but a result for that outcome is not reported in the registry record. The record separately lists serious-event counts and serious-event terms. Seriousness and severity are distinct concepts in general: seriousness concerns regulatory outcome criteria, while severity describes intensity. The record does not provide enough detail to equate its serious-event counts with the listed grade 3-or-higher outcome.

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("Treatment (Epacadostat, Pembrolizumab)")
n      <- c(14)
events <- c(3)
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  Treatment (Epacadostat, Pembrolizumab)  14  3  21.4  4.7  50.8  7.6  47.6  7.8  48.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and several secondary outcomes: adverse events of grade 3 or higher, progression-free survival, and overall survival. It does not report how many statistical hypotheses were planned, whether any outcomes were formally tested, or whether an approach to multiplicity was specified. When several outcomes are tested, general statistical practice may account for the increased chance of a false-positive finding across tests. Without the analysis plan, it is not possible to determine whether or how this issue was addressed in the study.

The primary endpoint description refers to exact 95% confidence limits that account for interim analysis and says they will be provided in the final report. The registry record does not report the interim-analysis schedule, number of looks at the data, stopping rules, or adjustment method. The mention of interim analysis in the endpoint description is not enough to reconstruct the procedure or its impact on inference.

Handling of missing outcome data is also not reported in the registry record. The primary endpoint is defined for evaluable patients, but the record does not state the criteria for evaluability, the number assessed, the number not assessed, or how missing assessments were treated. It does not describe imputation, sensitivity analyses, or whether participants were analyzed according to another population definition.

In general, analysis populations matter because exclusions or missing observations can change who contributes to an estimate. The registry’s listed enrollment of 14 does not establish that all 14 contributed to every endpoint. The statistical analysis plan, analysis populations, and missing-data procedures are not reported in the registry record, so the potential effect of incomplete observations cannot be assessed.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death nos (14.3%), anemia (7.1%), small intestinal obstruction (7.1%), gastrointestinal disorders - other (7.1%), ileal obstruction (7.1%).

The safety record lists 14 participants at risk for serious adverse events, with 7 affected, and 14 at risk for other adverse events, with 14 affected. It also lists 9 deaths. These are counts recorded for the treatment group; the registry information does not state that every event was caused by the regimen, nor does it provide enough detail to establish a causal relationship. The timing of events and deaths, their outcomes, and participant-level overlap are not reported in the registry record.

The listed serious terms include Death Nos at 14.3%, Anemia at 7.1%, Small Intestinal Obstruction at 7.1%, Gastrointestinal Disorders - Other at 7.1%, Ileal Obstruction at 7.1%, and Fatigue at 7.1%. The registry record does not explain the denominator or whether the term percentages refer to participants, events, or another reporting basis. These terms should therefore be read as recorded listings, not as a complete account of event frequency or attribution.

Grade 3 or higher adverse events were listed as a secondary outcome, but their result is not reported in the registry record. Seriousness and grade are not interchangeable concepts in general. The serious-event counts do not, by themselves, provide the missing grade 3-or-higher outcome or establish the severity of every listed event.

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

The registry record establishes that a completed phase II study assessed a combination of epacadostat and pembrolizumab in recurrent, persistent, or progressive ovarian clear cell carcinoma. It also defines a primary endpoint: complete or partial objective tumor response within 7 months of study entry among evaluable patients. These details describe the research question and the planned outcome framework.

The registry record does not report the primary response count, the number of evaluable patients, or an estimate with confidence limits. Therefore, the posted information cannot show how often the defined response occurred or how precisely it was estimated. The listed enrollment of 14 is not a substitute for the missing outcome denominator. The registry also does not report results for progression-free survival, overall survival, or the listed grade 3-or-higher adverse-event outcome.

The single-group, open-label design has no randomized comparator. Even if a response result were available, a response count in one group would describe what occurred in that group; it would not provide a controlled estimate of what would have happened under another treatment. The brief summary’s mention of usual treatment options is not evidence that participants were assigned to a comparison arm.

The adverse-event information provides counts and a list of serious-event terms, but it does not establish that any event or death was caused by study treatment. The available details also do not fully specify the denominators or event context for the listed percentages. Safety interpretation should remain descriptive.

In general, statistical evidence is shaped by both the observed estimate and its uncertainty, as well as by study design and analysis methods. Here, the central primary outcome estimate and its precision are not reported in the registry record. The record can therefore support a description of the study design, endpoint, and recorded safety counts, but not a numerical conclusion about the primary response outcome or a causal comparison with another treatment.

14. Why This Trial Matters Statistically

This study is statistically notable for the gap between a clearly named primary question and the outcome information available in the registry record. The endpoint specifies a response category, an assessment window, and a population described as evaluable patients. Yet the record does not report the response count, the evaluable denominator, or the confidence limits described as intended for the final report. A precise endpoint definition is useful, but it cannot replace the observed estimate needed to assess the result.

The single-group design also shapes what the study can answer. It can describe outcomes among participants receiving the combination, but it does not include a concurrent randomized control for estimating a comparative effect. This distinction matters when the brief summary mentions usual treatment: that background statement is not a trial comparison. Statistical interpretation must follow the actual design rather than the broader context in which the question is introduced.

The record further illustrates why enrollment, analysis population, and outcome reporting should be distinguished. It lists 14 enrolled participants, while the primary endpoint is defined for evaluable patients. The number of evaluable participants and the handling of missing assessments are not reported. Without them, a reader cannot establish how many participants contribute to the primary endpoint.

Finally, a completed study status does not mean that every outcome or analysis detail is included in the registry record. The missing response results, secondary outcome analyses, and statistical plan limit assessment of both the estimated outcomes and their uncertainty. This is a useful reminder that statistical conclusions depend not only on a study’s stated question, but also on transparent reporting of the analysis population, estimates, and methods.

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 primary limitation for interpretation is the absence of the primary-endpoint result in the registry record. The response count, the number of evaluable patients, and the exact 95% confidence limits described in the endpoint text are not reported. The result’s magnitude and precision therefore cannot be assessed from the posted record.

The study was single-group, open-label, and had no allocation. It has no concurrent randomized comparison group, so the design does not support a direct within-trial comparison against usual treatment. The registry’s brief summary mentions surgery, radiation, or cytotoxic chemotherapy as usual treatment options, but does not describe a comparison arm receiving them.

Although enrollment is listed as 14, the record does not report the primary analysis denominator or define evaluability beyond naming evaluable patients as the endpoint population. Missing-data handling and participant flow are not reported. These omissions make it difficult to determine how the enrolled population relates to the population contributing to the endpoint.

The statistical analysis plan, sample-size justification, interim-analysis details, and multiplicity approach are not reported in the registry record. The primary endpoint description mentions confidence limits accounting for interim analysis, but does not provide the interim procedure or limits. Results and analysis details for progression-free survival, overall survival, and grade 3-or-higher adverse events are also not reported.

The safety record provides event counts and selected terms, but does not establish causality or fully explain the denominator and context for the listed percentages. It also does not supply the information needed to treat serious-event counts as equivalent to the separately listed grade 3-or-higher outcome. These are limitations of the available registry information, not evidence that an unreported procedure or analysis was or was not conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing Whether the Combination of Two Immunotherapy Drugs Have Activity in Recurrent or Persistent Clear Cell Ovarian Cancer — NCT03602586.
• Registry record last updated 2024-07-26; status last verified 2024-06.
• Results first posted 2022-12-23.
• 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

The registry describes a completed phase II, single-group, open-label study of epacadostat plus pembrolizumab in recurrent or persistent ovarian clear cell carcinoma. Enrollment was 14, and the primary endpoint was complete or partial objective tumor response within 7 months of study entry among evaluable patients, assessed using RECIST version 1.1. The recorded study start was 2018-12-21 and primary completion was 2021-02-01.

The primary response result, evaluable population size, and confidence limits are not reported in the registry record. Progression-free survival, overall survival, and grade 3-or-higher adverse events are listed as secondary outcomes, but their results are not reported. The safety record lists 7 participants with serious adverse events among 14 at risk, 14 with other adverse events among 14 at risk, and 9 deaths. These counts do not establish causation. The record does not report a statistical analysis plan, sample-size justification, or missing-data procedures.