Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors (NCT03274661), a na phase 2 study. The primary outcome is Immune-related Objective Response Rate.

2. Clinical Question

The study title refers to tumors that are homologous recombination competent and deficient. However, the registry record does not describe how those categories were determined, whether they defined separate analysis groups, or how results were to be compared across them. The study is therefore best read as a single-group evaluation of pembrolizumab in a broad metastatic solid-tumor population, rather than as a reported comparison between repair-status groups.

The clinical question is also bounded by the eligibility context in the brief summary: participants had experienced progression after first-line standard chemotherapy, or had no standard chemotherapy option, and their tumor indication was not listed as an approved pembrolizumab indication. These details describe the intended population; they do not establish that every enrolled participant had the same prior treatment history or tumor characteristics. The registry record reports enrollment of 52 participants, but does not give the distribution of tumor types or repair status in the information available for this analysis.

3. Trial Design

This was a Phase II, single-group study with no randomized allocation and no masking. The listed intervention was pembrolizumab 200 mg Q3W, given intravenously on Day 1 of each 3-week cycle. The registry record lists an enrollment of 52 and a completed status. The recorded study start was 2017-11-03, and the primary completion date was 2020-10-20.

The planned primary outcome was immune-related objective response rate, assessed at 20 weeks. The response definition used immune-related Response Criteria (irRC), with complete or partial response determined from target lesions assessed by CT or MRI. The record also lists progression-free survival and overall response as secondary outcomes. It reports three outcome measures overall, but does not provide an analysis for them in the posted results.

Because the design has one treatment group, the study can describe outcomes among those treated, but it cannot by itself separate treatment-associated changes from the natural course of disease, measurement variation, or other influences. The absence of masking may also matter when outcome assessment involves clinical judgment, although the registry description identifies imaging-based lesion criteria for the primary outcome. The record does not say whether response assessments were independently reviewed or blinded.

The registry record does not report a planned sample-size justification, a statistical analysis plan, or interim analyses. The planning illustrations elsewhere use equal allocation between two arms, whereas the trial itself is listed as single-group; those illustrations should not be read as the study's design or as evidence of an actual randomized comparator. Likewise, the completed status indicates the recorded study status, not that the primary endpoint result is reported.

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

Analysis population for the primary outcome, as defined in the registry: Two participants were excluded from analysis: one was deemed not response-evaluable after a further review of baseline CT images demonstrated not clearly measurable disease; another deteriorated rapidly due to tumor progression within a week of the first dose of treatment.

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 Immune-related Objective Response Rate, measured over 20 weeks.

The primary endpoint is immune-related objective response rate at 20 weeks. It is defined as the percentage of participants who achieved complete or partial response using immune-related Response Criteria. The stated criteria use target lesions assessed by CT or MRI. Complete response requires disappearance of all lesions in two consecutive observations separated by at least 4 weeks. Partial response requires at least a 50% decrease in tumor burden from baseline, documented in two observations at least 4 weeks apart.

Objective response is used to describe tumor shrinkage according to prespecified lesion criteria. Expressing the outcome as a proportion would indicate how many response-evaluable participants met either response category by the stated assessment time. It does not, on its own, describe how long a response lasts, whether disease control continues, or how outcomes compare with a control group. The registry record lists the endpoint as a count of participants and gives its unit as participants, but does not post the response count or percentage.

The record notes that two participants were excluded from the primary analysis. One was judged not response-evaluable after review of baseline CT images found disease that was not clearly measurable. Another deteriorated rapidly because of tumor progression within a week of the first dose. The analysis population and handling of these exclusions are important to interpreting any response proportion; further details about those decisions are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as a single-group study. In general, a single-group analysis reports outcomes within the enrolled treatment group and does not estimate a randomized contrast with a control group. This design can describe observed outcomes, but the lack of a comparator means that changes cannot be attributed to treatment by comparison with what would have happened to a similar group under another condition. The registry record lists allocation as not applicable and masking as none.

What does the response endpoint measure?

The primary endpoint is a binary participant-level outcome: a participant either meets the complete or partial response definition by the stated assessment time or does not. The response criteria require repeated observations, which helps distinguish a sustained imaging change from a finding at only one assessment. In general, prespecified criteria improve consistency by setting rules for interpreting measurements. They do not eliminate variation in scans, assessment timing, or classification.

The registry record states that response is assessed at 20 weeks and that the response categories rely on CT or MRI assessment of target lesions. It describes complete response as disappearance of all lesions in two observations at least 4 weeks apart, and partial response as at least a 50% decrease in tumor burden from baseline in two observations at least 4 weeks apart. It does not report how often scans were scheduled, how non-target lesions were handled, or how missing or unevaluable assessments were classified.

How should a response proportion be interpreted?

In general, a response proportion is an estimate based on the participants included in its analysis. Its interpretation depends on both the count meeting the response definition and the analysis denominator. A confidence interval, when reported, describes the statistical uncertainty around an estimate under the method used; it is not a guarantee that the true value lies within the interval. No primary response estimate or confidence interval is reported in the registry record, so the precision of the intended endpoint cannot be assessed from the posted results.

The record says two participants were excluded from primary analysis, for reasons related to unclear measurability at baseline and rapid deterioration after the first dose. These are distinct reasons for not contributing to the analysis as described, but the record does not explain whether the exclusions were prespecified, whether other participants had missing assessments, or how the analysis population was otherwise defined. In general, exclusions after enrollment can affect an estimate if included and excluded participants have different outcome prospects. The available description is not enough to determine the direction or magnitude of any such effect.

What can be inferred from the planning illustrations?

The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are not described as the trial’s original design calculations. The study itself is listed as single-group, so an equal-allocation, two-arm illustration is not a description of how participants were assigned in this trial. Planning calculations are hypothetical estimates of requirements under stated assumptions, not observed power and not evidence that a study had a particular probability of detecting an effect.

In general, a planning calculation is sensitive to the effect size chosen, the statistical model, the error rate, and allocation assumptions. If the assumed effect is based on an observed effect, the resulting illustration can be optimistic or unstable because an observed estimate is subject to sampling variability. The posted information does not give numerical planning results in the registry record described for this analysis, nor does it report the study’s own sample-size justification. The planning assumptions therefore should not be treated as evidence that the completed study was adequately powered for its primary endpoint.

What does the absence of analyses mean?

The record lists three outcome measures and zero analyses. In general, an outcome definition and an analysis are different things: the definition specifies what should be measured, while the analysis reports how the observed data relate to the question. Without reported estimates, uncertainty measures, or test results, readers cannot assess the magnitude or precision of the primary outcome. This absence does not establish that no analysis was conducted outside the registry record; it means the analysis is not reported in the registry record.

For a time-to-event outcome such as progression-free survival, general statistical interpretation would depend on the event definition, censoring rules, follow-up, and analysis method. Those details and results are not reported in the registry record. Similarly, no method for adjusting for over-dispersion is specified; over-dispersion is a general concern when count variation exceeds what a model assumes, but the primary endpoint is described as a participant count rather than a reported rate model. No model details are available to assess.

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("Pembrolizumab 200 mg Q3W")
n      <- c(50)
events <- c(9)
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  Pembrolizumab 200 mg Q3W  50  9  18.0  8.6  31.4  9.8  30.8  9.8  30.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists immune-related objective response rate as the primary outcome and names progression-free survival and overall response as secondary outcomes. It reports three outcome measures but does not provide analyses for them. The record does not state whether the outcomes were tested as formal hypotheses, whether a hierarchy was used, or whether any adjustment for multiple comparisons was planned.

In general, testing several outcomes can increase the chance of a nominally notable result arising by chance if each is interpreted separately. Multiplicity procedures can control that risk, but the appropriate approach depends on the questions and analysis plan. No such procedure is reported. Since no analyses are posted, there are no reported p-values to interpret in light of multiplicity.

Missing-data handling is also not described. The primary endpoint notes two exclusions: one participant was deemed not response-evaluable after review of baseline CT images, and another deteriorated rapidly from tumor progression within a week of the first dose. The record does not state whether these rules were specified before analysis, how any other missing assessments were handled, or whether sensitivity analyses were performed. It also does not identify the full primary analysis population or its denominator.

These gaps matter because endpoint definitions, analysis populations, and missing-data methods jointly determine the meaning of an estimate. The registry record does not report enough information to assess whether the reported population, if any, followed an intention-to-treat principle or another analysis approach. That approach is not reported in the registry record.

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: abdominal pain (9.6%), dyspnea (5.8%), constipation (5.8%), vomiting (5.8%), nausea (3.8%).

The safety summary lists 19 of 52 participants with serious adverse events, 30 of 52 with other adverse events, and 38 deaths in the pembrolizumab group. It also lists serious-event terms with percentages: abdominal pain, 9.6%; dyspnea, 5.8%; constipation, 5.8%; vomiting, 5.8%; nausea, 3.8%; and ascites, 3.8%.

These are descriptive registry counts and percentages. The record does not specify the period over which they were collected, whether participants could contribute more than one event term, or how the listed terms were selected. It does not report whether events were judged related to treatment, nor does it provide a detailed grading or adjudication method. The death count has no stated cause or treatment attribution in the registry information. Therefore, the figures should not be interpreted as establishing that pembrolizumab caused an event or death. They describe events recorded for the study group, with important timing and attribution details not reported in the registry record.

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

The record establishes that a Phase II, single-group study evaluated pembrolizumab in adults with metastatic solid tumors in the eligibility context described, and that the primary endpoint was immune-related objective response at 20 weeks. It also specifies the response criteria and notes two exclusions from primary analysis. These details help define the question that the trial intended to address.

The record does not provide the primary response count or rate, an estimate of uncertainty, or analyses of the primary and secondary outcomes. It therefore does not show how many participants met the response criteria, how precise an estimate might be, or whether outcomes differed by homologous recombination status. The study title refers to competent and deficient tumors, but no subgroup definitions or comparative results are reported in the registry record.

Even if an outcome estimate were available, a single-group design would describe what was observed among participants who received the intervention; it would not provide a randomized estimate of what would have happened under a comparator. The posted information also does not include enough detail about missing assessments, analysis populations, or outcome assessment procedures to resolve those issues.

The safety counts offer a limited description of recorded serious and other adverse events and deaths. They do not establish causation, and the registry information lacks timing and attribution details. These data should be read as a report of observed events in the study group, rather than as a comparative estimate of risk.

Accordingly, the registry record supports understanding the trial’s design and measurement framework, but the posted results are insufficient for a quantitative conclusion about the primary clinical question. This is a limitation of the reported information, not evidence that a particular response outcome did or did not occur.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported endpoint result are both needed for statistical interpretation. The registry record gives a detailed operational definition for immune-related objective response, including imaging modalities, response categories, and the need for observations separated in time. Those rules describe how response was meant to be classified, but they cannot substitute for the response count, analysis denominator, or uncertainty estimate.

The record also highlights the importance of analysis populations. It identifies two exclusions from primary analysis and gives reasons, allowing readers to see that not all enrolled participants were considered response-evaluable. But without the final denominator and a fuller account of missing-data handling, the impact of those exclusions cannot be judged.

The single-group design is another key statistical feature. It can describe outcomes in the treated group but does not support a randomized treatment comparison. This is especially important when the study title raises a question about homologous recombination status: without reported group definitions and analyses, readers cannot infer that response differed between competent and deficient tumors.

Finally, the presence of secondary outcomes and safety summaries does not make the evidence complete. No outcome analyses are reported, and the safety information lacks details on timing and attribution. Taken together, the record is a useful example of how registry descriptions, study design, analysis reporting, and cautious interpretation each play separate roles in evaluating a clinical trial.

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 consequential limitation in the registry record is that the primary endpoint result is not reported. There is no response count, response proportion, confidence interval, or inferential analysis in the posted results. The record lists three outcome measures and zero analyses, leaving the central study question without a reported quantitative answer.

The population and analysis details are also incomplete. The study title refers to homologous recombination competent and deficient tumors, but the registry record does not define those groups, report their sizes, or provide group-specific outcomes. The two primary-analysis exclusions are described, but the complete analysis denominator, other missing assessments, and sensitivity analyses are not reported. The record also does not explain how tumor types were distributed across the enrolled population.

Because the study is single-group and unmasked, there is no randomized comparator to support a causal contrast, and the record does not describe independent or blinded response review. It does not report an analysis plan, sample-size justification, interim analyses, or multiplicity handling. While planning illustrations use assumptions for a two-arm design, those assumptions do not describe the single-group trial’s actual allocation.

The safety summary provides selected counts and event terms but not their collection period, treatment attribution, grading details, or the cause of deaths. These limitations restrict interpretation of both benefit-related outcomes and safety. They should be understood as gaps in the registry information, not as evidence about unreported study findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors — NCT03274661.
• Registry record last updated 2023-10-19; status last verified 2023-09.
• Results first posted 2023-10-19.
• 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.

19. Record Summary

NCT03274661 is a completed Phase II, single-group study sponsored by Baptist Health South Florida. Its recorded start date is 2017-11-03, and its primary completion date is 2020-10-20. The registry lists enrollment of 52 and pembrolizumab 200 mg by intravenous infusion every 3 weeks.

The primary outcome is immune-related objective response at 20 weeks, defined using immune-related Response Criteria. Progression-free survival and overall response are listed as secondary outcomes. Two participants were excluded from primary analysis for reasons described in the registry record. The posted results include selected adverse-event counts and terms, but no outcome analyses are listed. The primary response result, analysis plan, sample-size justification, and further details about missing data and event attribution are not reported in the registry record.