Evaluating Combination Immunotherapy for Advanced Cholangiocarcinoma With Pembrolizumab and PEG-Intron: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating Combination Immunotherapy for Advanced Cholangiocarcinoma With Pembrolizumab and PEG-Intron (NCT02982720), a na phase 2 study. The primary outcome is Asses Objective Response Rate (ORR) of All Patients Receiving Pembrolizumab and Sylatron Combination Therapy.

2. Clinical Question

The trial was intended to assess safety and efficacy of the combination in advanced cholangiocarcinoma after frontline chemotherapy had been unsuccessful or could not be tolerated. Its stated primary objective was objective response rate (ORR), defined by the best response category: complete response (CR) or partial response (PR) under RECIST1.1.

Because the design had one treatment group and no control group, the study could not make a direct randomized comparison with another treatment or with no combination therapy. Any response or safety observations would describe participants who received the combination in this study; they would not, on their own, establish how outcomes compare with another option.

The registry record states that no data were collected or analyzed for the primary objective because the study was terminated early by the funder. Enrollment was 4. The record therefore does not provide an observed ORR for answering the primary question. Adverse-event information is reported separately and should not be mistaken for evidence about the response endpoint.

3. Trial Design

This was a Phase II, multicenter, open-label, single-group study. The registry record lists allocation as not applicable and masking as none. All enrolled participants were assigned to the combination group; there was no randomized allocation or separate control group. Enrollment was 4, and the study status is terminated.

The regimen description states that Sylatron was administered subcutaneously at 200mcg weekly starting at week 1, while pembrolizumab was administered intravenously at 200 mg every 3 weeks starting week 4. These are the planned administration details in the record; the record does not establish that every participant received every planned dose or completed the regimen.

The study began on 2017-07-05, and the primary completion date is listed as 2018-02-09. The primary endpoint timeframe was 12 months. The registry record attributes the absence of primary endpoint data to early termination by the funder. It does not describe the funder’s reason for termination beyond that statement.

A single-group design can describe outcomes among participants who received the intervention, but it does not separate treatment effects from other influences or provide a concurrent control for comparison. With enrollment of 4 and no primary endpoint data, the planned response question cannot be answered from the posted primary results. The registry record lists five outcome measures and zero analyses. It does not report a statistical analysis plan, a sample-size justification, or planned interim analyses.

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: No data was collected or analyzed for this objective due to the early termination of the study by the funder.

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 Asses Objective Response Rate (ORR) of All Patients Receiving Pembrolizumab and Sylatron Combination Therapy, measured over 12 months.

The primary endpoint was objective response rate (ORR), with a timeframe of 12 months. The record defines ORR as the proportion of subjects whose best response was complete response (CR) or partial response (PR), determined by RECIST1.1. In general, a response endpoint classifies tumor change using specified criteria and summarizes the share of participants meeting the response definition.

Using the best response over a stated timeframe gives an endpoint that can summarize whether participants reached a response category during that period. The definition also makes clear that stable disease or progression is not counted as CR or PR for this endpoint. The registry record does not give additional details about imaging schedules, confirmation of response, or how assessments were handled if a participant lacked an evaluable assessment.

The primary endpoint was not reported as an observed result. The record says no data were collected or analyzed for this objective because of early termination by the funder. Consequently, there is no posted response proportion to interpret, and no estimate of its precision or uncertainty. The definition explains what the study intended to measure, but it cannot substitute for an observed outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines what statistical conclusions can be drawn. This was a single-group Phase II study with no masking and no separate comparator. In a single-group study, outcome summaries describe the participants who received the intervention. General statistical principle: a concurrent control group helps distinguish an intervention-associated outcome from changes that could occur for other reasons. Because this study had no control group, it cannot provide a randomized contrast.

What does an objective response rate measure?

The primary measure was the proportion of participants whose best response was CR or PR according to RECIST1.1 during the 12-month timeframe. A proportion is a summary of how many participants meet a defined outcome relative to the group being assessed. General statistical principle: an estimate of a proportion is more informative when accompanied by an interval describing its uncertainty. The record does not report an ORR estimate or interval, because it states that no data were collected or analyzed for this objective.

What does the missing primary result imply?

A missing result must be distinguished from an observed result that equals zero. In this record, the stated reason is early termination by the funder, and the record says no data were collected or analyzed for the primary objective. It does not say that participants were assessed and none responded. As a result, a response estimate cannot be reconstructed from the registry entry, and no test of a response hypothesis can be interpreted.

How should adverse-event counts be read?

The adverse-event record gives participant counts at risk and affected, along with a death count and selected event terms with percentages. These are descriptive safety summaries. General statistical principle: a count or percentage in a treated group does not by itself show that treatment caused the event. Causal attribution requires context about event definitions, timing, exposure, and other evidence; those details are not fully reported in the registry record. Nor does a single-group summary provide a comparative safety estimate.

What does a confidence interval contribute?

General statistical principle: a confidence interval represents uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies within the interval, nor does it correct for design limitations or missing outcomes. Since no primary response estimate is reported, there is no interval for the intended primary endpoint to interpret. The record also does not report inferential analyses for the outcomes.

Why do analysis populations matter?

In clinical trials, different analysis populations can be defined according to enrollment, treatment received, or availability of outcome assessments. General statistical principle: the population used for an analysis affects what that analysis describes. The registry record does not report defined analysis populations for the primary endpoint, or how participants with missing assessments would have been handled. It is therefore not possible to determine an intended denominator for an efficacy analysis beyond the endpoint’s general definition.

What can be said about planning assumptions?

The registry record does not report the trial’s own sample-size justification, target enrollment, or power calculation. Planning illustrations based on an observed effect, when available, are hypothetical design calculations rather than evidence about the study’s actual power. They do not recover an absent endpoint or show whether the trial was adequately planned. No observed-effect estimate for the primary endpoint is reported in this record, so there is no primary result on which to base such an interpretation.

The registry record lists five outcome measures and zero analyses. It does not report the statistical methods used for analyzing the safety summaries, adjustments for covariates, treatment of multiple endpoints, or interim analyses. Those omissions limit assessment of the analysis choices, but they do not justify assuming that any particular method was used.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures, including the primary ORR objective and secondary outcomes related to progression-free survival, overall survival, adverse events, serious adverse events, and serious adverse events leading to treatment discontinuation (death). It records zero analyses. The record does not describe a multiplicity strategy, such as a prespecified ordering of tests or an adjustment for testing multiple endpoints. Without that information and without reported inferential results, the consequences of multiple testing cannot be assessed.

The primary endpoint has no analyzed result because the registry states that no data were collected or analyzed for that objective following early termination by the funder. This should be read as an unavailable primary result, not as a zero response estimate. The record does not report how many participants had outcome assessments, whether any assessments were incomplete, or how missing endpoint information would have been handled.

Analysis populations are not described in the registry record. It does not specify whether the planned efficacy analysis would have included all enrolled participants, only participants who received treatment, or another defined group. It also does not report an approach to missing safety follow-up or incomplete exposure information. These are important distinctions because the analyzed group and handling of absent observations affect the interpretation of estimates.

General statistical principle: missingness can affect an estimate when the participants with observed data differ from those without observed data. The pattern and reasons for missing information help assess that possibility. The record identifies early study termination as the reason the primary objective had no data collected or analyzed, but further details about participant follow-up and missingness are not reported in the registry record. No assumptions about those details can be evaluated from the posted results.

11. 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: alanine aminotransferase increased (50.0%), fever (50.0%), aspartate aminotransferase increased (25.0%), blood bilirubin increased (25.0%).

The adverse-event record lists 4 participants at risk for serious adverse events and 4 affected. For other adverse events, it also lists 4 at risk and 4 affected. The reported death count is 1. These figures describe the recorded experience in the treatment group; they do not establish whether an event was caused by pembrolizumab, Sylatron, the underlying condition, or another factor.

The listed serious-event terms include alanine aminotransferase increased and fever, each reported as 50.0%, and aspartate aminotransferase increased and blood bilirubin increased, each reported as 25.0%. The registry entry does not provide further detail in these summaries about event timing, severity grading, duration, treatment exposure, or whether individual participants experienced more than one event. Percentages for individual terms should therefore be read as registry-reported frequencies, not as a basis for comparing treatments.

General statistical principle: safety summaries are descriptive unless the design and analysis support a comparative interpretation. With no control group, these counts do not quantify excess risk attributable to the combination. The record’s adverse-event figures also do not resolve the missing primary response result.

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

The registry record documents a Phase II investigation of pembrolizumab and Sylatron in advanced cholangiocarcinoma after progression on or inability to tolerate frontline chemotherapy. It describes a single-group, open-label design and reports enrollment of 4. It also gives a planned regimen and a 12-month primary endpoint timeframe.

For efficacy, the central finding is that no primary endpoint data were collected or analyzed because the study was terminated early by the funder. The objective response rate therefore has no reported estimate. This does not mean that the observed response rate was zero, and it does not demonstrate that the combination was effective or ineffective. The primary question remains unanswered by the posted results.

The adverse-event counts provide a limited description of safety events recorded among participants in the combination group, including a reported death. They cannot establish treatment causality or compare the combination with another regimen. The record does not give the detail needed to assess the timing and severity of all events or the extent of treatment exposure.

General statistical principle: a study’s design and completeness of outcome data constrain the conclusions that can be drawn, regardless of the clinical importance of its question. Here, there is no randomized comparator and no analyzed primary response outcome. The posted results therefore do not support a comparative treatment-effect estimate, a precise response estimate, or a conclusion about the balance of benefit and harm. They document the study’s intended question, early termination, and reported adverse-event experience, while leaving the primary efficacy question unresolved.

13. Why This Trial Matters Statistically

This trial illustrates a central issue in clinical-trial interpretation: a carefully defined endpoint is not the same as an observed result. ORR was defined using CR and PR under RECIST1.1 over 12 months, but the registry states that no data were collected or analyzed for that objective. Readers must therefore distinguish the planned measurement from evidence answering the clinical question.

The design also matters. A single-group, open-label study can report experience among participants who received the combination, but it does not create a randomized comparison. That limitation is particularly relevant when interpreting safety counts: the figures describe events in the enrolled group, not the difference in event risk between treatments.

Enrollment was 4, and the study was terminated early by the funder. These registry entries place the reported information in context, but they do not explain why the study ended beyond the registry’s statement. The record does not report a sample-size justification, analysis plan, interim analyses, or defined analysis populations. Statistical interpretation should not fill those gaps with assumptions.

General statistical principle: transparent reporting of design, analysis, and missing outcomes allows readers to judge how strongly results address a research question. In this record, the primary endpoint’s absence is as important to interpretation as its definition. The result is not a negative response finding; it is an unavailable efficacy result, alongside descriptive safety information. Keeping those categories separate prevents the adverse-event summaries from being mistaken for an answer about tumor response.

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 primary limitation is that the registry reports no data collected or analyzed for the primary ORR objective because of early termination by the funder. There is consequently no response estimate or uncertainty interval to interpret. Enrollment was 4, limiting the scope of the reported experience.

The single-group, open-label design includes no concurrent comparator. It cannot provide a randomized estimate of the combination’s effect relative to another treatment. The record also lists allocation as not applicable and masking as none. The absence of a comparator applies to interpretation of both efficacy and safety.

The registry record does not describe the reason for termination beyond attributing it to the funder, the amount of follow-up achieved, or the treatment exposure actually received by each participant. It does not report how the planned endpoint would handle participants without an evaluable assessment, define analysis populations, or specify statistical methods for the outcomes. Sample-size justification and interim analyses are also not reported in the registry record.

The adverse-event summaries are limited to reported counts and selected terms. Additional information about event timing, grading, duration, and attribution is not stated in these summaries. The reported death count does not, by itself, identify cause or establish a relationship to treatment. These limitations prevent a fuller assessment of safety and leave the primary efficacy question unanswered.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating Combination Immunotherapy for Advanced Cholangiocarcinoma With Pembrolizumab and PEG-Intron — NCT02982720.
• Registry record last updated 2022-02-16; status last verified 2022-02.
• Results first posted 2019-06-05.
• 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.

18. Record Summary

NCT02982720 is a Phase II, multicenter, open-label, single-group study of pembrolizumab and Sylatron in advanced cholangiocarcinoma. The intended population had progressed on or could not tolerate frontline chemotherapy. Enrollment was 4, and the registry status is terminated.

The primary endpoint was ORR, defined as best response of CR or PR under RECIST1.1 over 12 months. The registry states that no data were collected or analyzed for this objective because of early termination by the funder. No primary response estimate is reported.

The adverse-event record lists 4 participants affected by serious adverse events, 4 affected by other adverse events, and 1 death. These are descriptive counts, not comparative or causal estimates. The registry record does not report an analysis plan, sample-size justification, or defined analysis populations.