A Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors (NCT04925947), a na phase 2 study. The primary outcome is Anti-tumor Activity of KN046 in Subjects With Thymic Carcinoma, Determined by Subject Disease Response Rate Defined by the RECIST 1.1 Criteria..

2. Clinical Question

The clinical question is descriptive: among participants matching the recorded study population and receiving KN046, how many met the specified disease-response criteria during the stated timeframe? A count can describe what occurred among those enrolled, but without a comparator it cannot by itself distinguish a treatment-related effect from other explanations for observed disease changes.

The registry also identifies safety, tolerability, duration of response, progression-free survival, and overall survival as secondary outcomes. These outcomes address different aspects of treatment experience and disease course; they are not interchangeable with the primary response count. Their results are not reported in the registry record. The record does not provide enough detail to determine how the eligibility criteria were applied or how representative the participants were of other patients with thymic carcinoma.

3. Trial Design

This was a Phase II study of KN046 in patients with thymic carcinoma who failed immune checkpoint inhibitors. The registry classifies it as a single-group study, with no masking and allocation listed as not applicable. There was no randomized or concurrent control group. As a result, the trial design can describe outcomes among people who received KN046, but does not support a direct within-trial comparison with an alternative treatment or with no treatment.

The study planned to administer KN046 intravenously every 2 weeks. The stated primary outcome was anti-tumor activity, defined as the number of participants with a disease response by RECIST 1.1, with a timeframe of up to 8 weeks. The registry lists safety, tolerability, duration of response, progression-free survival, and overall survival as secondary outcomes. It does not report results for these endpoints.

The record lists an enrollment of 4 and a status of terminated. The study start date is 2021-12-13, and the primary completion date is 2023-05-05. The reason for termination is not reported in the registry record. The enrollment figure indicates the number recorded for the study, not the number necessarily assessed for each endpoint; endpoint-specific analysis populations are not reported.

Important design details are not reported in the registry record, including the dose of KN046, eligibility criteria beyond the broad population description, the intended sample size, the rationale for that sample size, and whether interim analyses were planned or conducted. The record also does not describe a statistical analysis plan or provide the details needed to assess how the stated outcomes were evaluated. These gaps limit interpretation of the study's design and conduct beyond the classifications and dates recorded above.

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

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 Anti-tumor Activity of KN046 in Subjects With Thymic Carcinoma, Determined by Subject Disease Response Rate Defined by the RECIST 1.1 Criteria., measured over Up to 8 weeks.

The primary endpoint is the anti-tumor activity of KN046, expressed as the number of participants with a disease response defined by RECIST 1.1. Its stated timeframe is up to 8 weeks. This is a count-based outcome: it records how many participants met the response definition, rather than measuring the size of a response on a continuous scale. The registry does not report a response count, response proportion, or endpoint analysis.

RECIST 1.1 is the response framework named in the registry record. In general, a prespecified response framework aims to apply consistent criteria when classifying changes in disease. That consistency can make an outcome easier to interpret than an informal or unstandardized assessment. The registry record does not provide further details about the assessment schedule, how response was confirmed, or how missing or unevaluable assessments were handled.

A response count is useful for describing the observed outcome in the enrolled group, but its interpretation depends on the number assessed and the rules used to classify each participant. The total enrollment is 4, but the number included in the primary endpoint analysis is not reported in the registry record. Without the endpoint result and its uncertainty, the record does not establish how common response was in this study or how precisely it was estimated. The endpoint also does not, by itself, establish that any observed response was caused by KN046, because this was a single-group study without a concurrent comparator.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as a count of participants with an event, in this case a disease response defined by RECIST 1.1. The reported unit is a count of participants, and the timeframe is up to 8 weeks. The record lists no analyses. It does not report a response count, an effect estimate, an uncertainty interval, a test statistic, or a p-value. Consequently, there is no posted primary endpoint analysis to interpret statistically.

What does a count-based response outcome describe?

A count records how many participants meet a stated event definition. For a response outcome, the definition determines which participants qualify as having a response. A count can be presented alone, or it can be related to the number of participants assessed to form a proportion. The registry record gives an overall enrollment of 4 but does not report the primary response count or the number assessed for that outcome. A response proportion should not be inferred from enrollment alone.

In general, a proportion is an estimate of an event frequency in the population represented by the study. Its uncertainty depends in part on how many participants contribute evaluable outcome data and on the observed count. With few observations, a small change in the count can materially alter the estimated frequency. A confidence interval is a way to express uncertainty around an estimate under specified statistical assumptions; it is not a guarantee that the true value lies within the interval. No such interval for the response outcome is reported in the registry record.

Why does the single-group design matter?

A single-group study measures outcomes in participants receiving the intervention without a concurrent control group. Its estimates can describe what was observed in that group, but there is no direct randomized contrast in the study to estimate how outcomes would have differed under another condition. General statistical interpretation therefore separates an observed outcome from a causal treatment effect. In this study, masking is listed as none, and allocation is listed as not applicable. These design features are relevant context, but the registry record does not provide enough information to assess how outcome assessment was conducted or whether any safeguards were used.

Because there is no randomized comparison, a difference from an external benchmark would require a defined benchmark and assumptions about comparability. No such comparison or benchmark is reported in the registry record. No comparative treatment-effect estimate should be attributed to this study.

What can the record say about statistical precision?

Precision describes how much uncertainty surrounds an estimate. It is often conveyed with a confidence interval, while a standard error is another measure of sampling uncertainty. These quantities depend on the analysis and the available observations. The registry record does not report a primary response estimate or an uncertainty measure, so precision cannot be evaluated from the posted efficacy information. The small enrollment of 4 also means the study has a limited number of observations for describing response and safety, though the exact uncertainty cannot be quantified without the relevant endpoint results and analysis.

A p-value, when used, measures how incompatible observed data are with a specified statistical model or null hypothesis, under the assumptions of the test. It is not the probability that a hypothesis is true, and it does not measure the size or clinical importance of an effect. No p-value or testing result is reported in the registry record. The absence of a reported p-value does not imply a particular statistical conclusion.

How should sample-size illustrations be understood?

General planning calculations answer a design question: how many participants might be needed under stated assumptions to detect a specified effect with a chosen error rate and power. They are not observed outcomes, and they are not evidence that a study had a particular probability of success after it was completed. The assumptions recorded for the planning illustration specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Time-to-event planning calculations are described as total event counts; other calculations are described as participants per arm.

Those assumptions describe a planning framework, not the design of this single-group study. They should not be interpreted as a sample-size justification for the trial, a planned analysis, or observed power. The registry record does not report the study's own sample-size justification. Since the primary response result and its analysis are not reported, the observed effect underlying any planning illustration cannot be evaluated from the registry record. Planning figures are hypothetical illustrations, not results from participants.

What do the safety counts represent?

The registry lists 4 participants at risk for serious adverse events and 3 affected. It also lists 4 participants at risk for other adverse events and 3 affected, with 0 deaths. These counts are descriptive. They do not show whether events were related to treatment, when events occurred, or how multiple events within a participant were handled. The listed serious-event terms and percentages add detail about recorded events, but the record does not provide enough information to reconstruct an event-level analysis.

In general, over-dispersion refers to greater variability in count data than a simple statistical model assumes. It can matter when modeling event counts, because a model that understates variability may give confidence intervals that are too narrow or tests that are too optimistic. The registry record does not report a count model, an over-dispersion assessment, or any model-based safety analysis. This general consideration cannot be used to infer what methods were applied in this study.

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("KN046")
n      <- c(4)
events <- c(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  KN046  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and five secondary outcomes: safety, tolerability, duration of response, progression-free survival, and overall survival. When several outcomes are examined, multiplicity can arise because repeated statistical tests or estimates increase the chance of an apparently notable finding by chance. General approaches to multiplicity include defining a primary endpoint in advance, adjusting testing procedures, or interpreting secondary outcomes as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any adjustment was planned or conducted.

The registry record reports zero analyses. It does not report results for the primary endpoint or the listed secondary outcomes, nor does it describe analysis populations. The number enrolled is 4, but the record does not say how many participants were included in each endpoint analysis or whether all enrolled participants were assessed. It also does not report whether an intention-to-treat, treated, evaluable, or other analysis population was defined.

Missing-data handling is not reported in the registry record. That includes how missing response assessments, incomplete follow-up, or participants without an evaluable endpoint would be treated. General statistical interpretation depends on these choices because excluding participants or assigning outcome status can affect an estimate. No assumptions about missingness or imputation can be inferred from the registry record.

The record also does not describe an interim analysis plan, stopping rules, or the statistical analysis plan. The status is terminated, but the reason for termination and any analysis-related decisions are not reported. Without those details, it is not possible to assess whether outcome selection, missing observations, or repeated looks at data affected interpretation.

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: absolute lymphocyte count decreased (50.0%), back pain (25.0%), abdominal pain (25.0%), leukocytosis (25.0%), gastroesophageal reflux disease (25.0%).

The registry record lists 4 participants at risk for serious adverse events, with 3 affected. For other adverse events, it likewise lists 4 at risk and 3 affected. The record lists 0 deaths. These figures describe the reported safety experience in this small enrolled group; they are not comparative rates and do not establish that KN046 caused an event.

The leading serious-event terms listed are Absolute Lymphocyte Count Decreased at 50.0%, Back Pain at 25.0%, Abdominal Pain at 25.0%, Leukocytosis at 25.0%, and Gastroesophageal reflux disease at 25.0%. The percentages are registry-listed values. The record does not explain whether participants could contribute more than one term, whether terms overlap, or the specific denominator used for each term, so these percentages should not be converted into inferred event counts.

General statistical context: an adverse-event count is not the same as a count of affected participants, because one participant may experience more than one event. Seriousness and severity are also distinct concepts. The registry describes tolerability in terms of severity assessed using NCI Common Terminology Criteria for Adverse Events, Version 5.0, but it does not provide severity results in the record summarized by these figures. Timing, duration, treatment relationship, and event-level details are not reported. The small group and lack of a comparator limit any broader safety comparison.

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

The registry record establishes that this was a terminated Phase II, single-group study of KN046 in thymic carcinoma after prior immune checkpoint inhibitor treatment. It records enrollment of 4 participants, intravenous administration every 2 weeks, and a primary response endpoint defined using RECIST 1.1 over up to 8 weeks. It also records serious adverse-event information and 0 deaths.

The main efficacy question cannot be answered from the posted results because the registry record does not report the primary response count or any analysis of that endpoint. No estimate of response frequency or its uncertainty is available in the record. The secondary outcomes are listed, but their results are also not reported. The lack of posted analyses should be understood as a limitation of the registry record, not as evidence that a particular outcome did or did not occur.

Even if an outcome count were available, a single-group study would describe the experience of participants receiving KN046 rather than provide a randomized comparison. The design cannot directly separate treatment effects from other influences on observed disease response or safety. In general, causal interpretation requires a suitable comparison and defensible assumptions; the registry record does not report such a comparison.

The safety information indicates that serious adverse events were recorded among participants in the study. These counts do not establish treatment causation, and the terms and percentages do not provide a complete account of timing, severity, relatedness, or repeated events. The record does not report the reason the study was terminated, so termination should not be interpreted as a judgment about efficacy or safety.

Overall, the posted information supports a description of the trial's design, enrollment, dates, and selected safety counts. It does not support a conclusion about the frequency of tumor response, the precision of an efficacy estimate, comparative effectiveness, or the cause of reported adverse events. Missing efficacy results and limited design detail are central to interpreting what can and cannot be learned from this registry record.

14. Why This Trial Matters Statistically

This study illustrates a fundamental distinction in clinical-trial interpretation: a trial can identify an important clinical question without posting the results needed to answer it. The registry names a primary endpoint, a response definition, and a timeframe, but does not report the response count or an analysis. Without those items, the endpoint cannot be summarized as an observed efficacy estimate or judged for precision.

It also highlights why study design determines the scope of statistical claims. A single-group study can describe outcomes among those enrolled, but it does not contain a concurrent control group for a direct treatment comparison. The absence of masking is another recorded design feature; the record does not report details that would establish how assessments were protected from potential influence. These issues matter when considering how outcomes were generated and what conclusions the design could support.

The enrollment of 4 underscores the importance of distinguishing a small descriptive experience from a stable estimate of outcome frequency. General statistical reasoning indicates that estimates based on few observations are uncertain, but the precise uncertainty cannot be quantified without the endpoint result and an analysis. A count of affected participants likewise cannot stand in for a full event-level safety analysis.

Finally, the record shows why completeness is part of statistical interpretation. The trial is marked terminated, yet its reason for termination, analysis populations, missing-data methods, sample-size justification, multiplicity approach, and statistical analysis plan are not reported. These absences do not prove that the corresponding plans or analyses did not exist; they limit what can be independently evaluated using the registry record. Accurate interpretation therefore requires separating recorded details from unanswered questions.

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 is the absence of posted efficacy results. Although the registry defines a primary response endpoint, it does not report how many participants responded, how many were assessed, or any estimate of response frequency. It also reports zero analyses. Statistical precision and the relationship between the stated endpoint and observed outcomes therefore cannot be evaluated.

Enrollment was 4, leaving a limited set of observations for describing outcomes in this study. The registry record does not provide participant characteristics or endpoint-specific denominators, so it is not possible to assess who contributed to each result or how broadly the enrolled group represents the intended population. The record's broad population description does not replace detailed eligibility criteria.

The single-group design has no concurrent comparator, and masking is listed as none. As a result, the record does not support a direct randomized comparison, and the registry does not provide enough information to assess the conduct of outcome assessments. The reason for termination is not reported, so no explanation for the study's status should be assumed.

Other limitations include absent information on the study's own sample-size rationale, statistical analysis plan, interim analyses, multiplicity handling, analysis populations, and missing-data methods. The registry lists secondary outcomes but does not report their results. Safety information is limited to selected counts and serious-event terms; event timing, severity results, treatment relationship, and details of repeated events are not reported. These limitations constrain interpretation of both efficacy and safety beyond the descriptive information in the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of KN046 in Patients With Thymic Carcinoma Who Failed Immune Checkpoint Inhibitors — NCT04925947.
• Registry record last updated 2024-04-16; status last verified 2024-03.
• Results first posted 2024-04-16.
• 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 record describes a Phase II, single-group study of KN046 for patients with thymic carcinoma who failed immune checkpoint inhibitors. KN046 was to be administered intravenously every 2 weeks. The primary endpoint was the number of participants with a disease response by RECIST 1.1, over up to 8 weeks. Enrollment was 4; the study is listed as terminated, with a start date of 2021-12-13 and primary completion date of 2023-05-05.

The record lists safety, tolerability, duration of response, progression-free survival, and overall survival as secondary outcomes. It reports serious adverse events in 3 of 4 participants at risk and 0 deaths, but does not report the primary response result or any statistical analyses. The reason for termination, analysis populations, missing-data approach, multiplicity plan, and statistical analysis plan are not reported in the registry record.