CHIO3 Trial: CHemotherapy Combined With Immune Checkpoint Inhibitor for Operable Stage IIIA/B Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CHIO3 Trial: CHemotherapy Combined With Immune Checkpoint Inhibitor for Operable Stage IIIA/B Non-Small Cell Lung Cancer (NCT04062708), a na phase 2 study. The primary outcome is N2 Nodal Clearance (N2NC).

2. Clinical Question

3. Trial Design

CHIO3 is registered as a phase II, single-group trial with open-label masking and an enrollment of 38. The registry status is active, not recruiting. The record gives a start date of 2021-03-10 and a primary completion date of 2025-02-24. These registry entries describe the study's planned and administrative characteristics; they do not provide an observed primary endpoint result.

Participants receive a sequence of treatments: neoadjuvant platinum doublet chemotherapy plus durvalumab, followed by surgery, postoperative radiation, and adjuvant durvalumab for 13 cycles. The intervention listings also identify durvalumab, surgery, and radiotherapy. Because this is a single-group study, there is no concurrent comparison arm. The historical 30% rate for platinum doublet chemotherapy alone is the stated reference for the objective, not a control group enrolled alongside the trial participants.

The primary endpoint is N2 nodal clearance among participants who completed neoadjuvant therapy and had nodal clearance evaluated at resection. That definition means the endpoint population depends on completing treatment and reaching resection with an assessment. The registry record does not report how many participants met those conditions or how participants without an assessment were handled.

The registry lists secondary outcomes covering treatment-related adverse events, radiographic response, major pathologic and complete pathologic response, event-free survival, overall survival, complete resection, and postoperative complications. The record does not report the statistical plan for these outcomes or provide analysis results for them. An allocation method beyond the single-group model is not reported in the registry record; the record's allocation entry is NA.

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.

Enrolled

Reasons for not completing this period:

Neoadjuvant Therapy

Reasons for not completing this period:

Resection

Analysis population for the primary outcome, as defined in the registry: Patients who completed neoadjuvant therapy and had nodal clearance evaluated at resection are evaluable for N2NC

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 N2 Nodal Clearance (N2NC), measured over 3 years 11 months.

N2 nodal clearance (N2NC) is the primary endpoint. It is expressed as a percentage of participants, and the registry defines who is evaluable: patients who completed neoadjuvant therapy and had nodal clearance assessed at resection. The clinical question is whether the treatment sequence can achieve N2 nodal clearance at the stated objective of 50% or greater, compared with the historical 30% rate for platinum doublet chemotherapy alone.

Pathologic assessment at resection makes this endpoint a measure of what is found in the nodes after induction treatment, rather than a measure based only on imaging. In general, a response endpoint can provide an earlier assessment of treatment activity than outcomes that require longer follow-up. It does not, by itself, establish what happens to survival or whether an effect on the endpoint translates into a longer-term benefit. Those are separate outcomes, and event-free survival and overall survival are listed as secondary outcomes in this registry record.

The endpoint is conditional on reaching resection and having nodal clearance evaluated. That makes the evaluable group important to interpretation: the percentage among evaluable participants may not describe every participant who started the treatment sequence. The registry record does not report the observed N2NC percentage, the number evaluable, or a confidence interval for the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design permit? This trial assigns the described treatment sequence to one group and has no concurrent control group. In general, a single-group study can describe outcomes among participants receiving the regimen and can compare an estimate with a prespecified or historical reference. It cannot provide the same direct protection against group differences that random assignment to concurrent treatments offers. Differences between the trial and historical patients, assessment practices, or care contexts can affect a historical comparison. The registry record does not report a randomized design or a concurrent comparator.

How should the primary endpoint be understood? N2 nodal clearance is a binary outcome at the participant level: a participant either meets the clearance definition or does not. The registry expresses the endpoint as a percentage and defines the evaluable group as people who completed neoadjuvant therapy and had nodal clearance assessed at resection. In general, a percentage for a binary outcome is an estimate of the proportion meeting the endpoint in the analyzed population. Its precision depends on the number of participants with an evaluable outcome and on the observed proportion. The record does not report either the observed proportion or the evaluable count.

What would a confidence interval add? In general, a confidence interval communicates uncertainty around an estimated quantity. A narrow interval indicates greater precision than a wide interval, while the interval's location helps readers assess which values remain compatible with the data under the method used. It is not a guarantee that the true value lies within the interval. No confidence interval for N2NC is reported in the registry record, so the precision of the primary endpoint cannot be assessed from the recorded information.

What is the role of the historical benchmark? The stated historical N2 nodal clearance rate is 30%, and the trial objective is 50% or greater. These figures frame the question the study was designed to address. They do not constitute an observed between-group estimate, and they do not supply the trial's outcome. A valid interpretation of a single-group estimate against history depends on whether the historical experience is sufficiently comparable; the registry record does not report details that permit that comparability to be assessed.

How do the planning assumptions relate to the design? The record describes sample-size planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detecting a stated fraction of the observed effect. It also specifies that sample-size illustrations for non-time-to-event outcomes are expressed as participants per arm. These are planning assumptions for illustrations, not a description of this trial's single-group enrollment or an observed power calculation. The record specifically cautions that such sample sizes are planning illustrations, never observed power. No numeric planning result is reported in the registry record, and the observed primary effect needed to interpret such an illustration is not reported there.

Why does the endpoint population matter? The endpoint is evaluated at resection after neoadjuvant treatment, so it is not automatically available for every person who begins treatment. In general, excluding people without an evaluable endpoint can change the composition of the analysis group. This does not show that such exclusions occurred in a particular way; it identifies why the evaluability definition and the number assessed matter. The registry record does not report a missing-data method, a rule for participants without resection assessment, or a broader analysis population for N2NC.

What can be inferred from the absence of analyses? The record indicates 0 analyses. It therefore contains no reported inferential result for the primary endpoint in the registry record recorded: no test statistic, p-value, confidence interval, or estimate. In general, a statistical test and an estimate answer related but different questions. A test assesses compatibility with a specified null model under stated assumptions, while an estimate describes the magnitude and direction of the observed quantity. Neither can be interpreted without the corresponding analysis details. The statistical plan, including any model or test for N2NC, is not reported in the registry record.

How should multiple outcomes be considered? The registry lists multiple secondary outcomes alongside the primary endpoint. In general, evaluating many outcomes can increase the chance of at least one apparently notable result if each is tested independently without adjustment. Whether and how to address that issue depends on the analysis plan and the intended interpretation of each outcome. The registry record does not report multiplicity adjustments, outcome hierarchies, or analysis results. No claim about a particular testing strategy is warranted from the listed outcomes alone.

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")
n      <- c(30)
events <- c(22)
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  30  22  73.3  54.1  87.7  55.6  85.8  55.4  85.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists N2 nodal clearance as the primary endpoint and identifies secondary outcomes for treatment-related adverse events, radiographic response, major pathologic response and pathologic complete response, event-free survival, overall survival, complete resection, and postoperative complications. It reports 8 outcome measures and 0 analyses. No inferential results for these outcomes are reported in the registry record.

When several outcomes are examined, multiplicity can matter: in general, testing multiple hypotheses without an adjustment can increase the chance of finding at least one apparently positive result by chance. The appropriate approach depends on which outcomes are confirmatory, the testing hierarchy, and the analysis plan. A multiplicity procedure or hierarchy is not reported in the registry record, so it is not possible to determine how the outcomes were intended to be interpreted together.

The primary endpoint definition specifies that patients who completed neoadjuvant therapy and had nodal clearance evaluated at resection are evaluable for N2NC. This identifies an endpoint-specific analysis population, but it does not explain how participants without an assessment are handled. A missing-data approach, imputation rule, and analysis population beyond the stated evaluability definition are not reported in the registry record.

The record does not report interim analyses, stopping rules, or a statistical analysis plan. Those details should not be inferred from the phase or stated objective. The absence of reported methods leaves uncertainty about how incomplete observations and multiple outcomes would be handled in formal analyses.

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: lung infection (16.7%), meningitis (16.7%), skin infection (16.7%), alanine aminotransferase increased (16.7%), presyncope (16.7%).

The registry records serious and other adverse-event fields separately for the periods labeled Pre Amendment 3 and Post Amendment 3. For Pre Amendment 3, the serious-event fields list 6 at risk and 2 affected; the other-event fields list 6 at risk and 6 affected; deaths are listed as 1. For Post Amendment 3, the serious-event fields list 31 at risk and 16 affected; the other-event fields list 31 at risk and 26 affected; deaths are listed as 9. These are the recorded counts, not a comparison between randomized groups.

The registry also lists Lung infection, Meningitis, Skin infection, Alanine aminotransferase increased, Presyncope, and Syncope among the top serious terms, each with 16.7%. The record does not report the denominators or whether participants could contribute to more than one term in that listing. These terms and percentages should therefore be read as registry-reported safety details, not added together or treated as mutually exclusive categories.

In general, adverse-event counts describe events recorded during study follow-up; they do not by themselves establish that treatment caused an event. The registry record does not provide event-level timing, exposure-adjusted rates, or a causal assessment. Differences between the amendment-period groups should not be interpreted as treatment comparisons, and the record does not provide a like-for-like control group.

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

The registry record conveys a clinical question and study design, but it does not report the primary endpoint result. The study objective is to assess whether N2 nodal clearance reaches 50% or greater after neoadjuvant platinum doublet chemotherapy combined with durvalumab, using a historical 30% rate for chemotherapy alone as its reference. Those figures are the stated objective and benchmark, not a reported treatment effect. No observed N2NC percentage or inferential analysis is reported in the registry record.

As a single-group phase II study, CHIO3 can be understood as an evaluation of outcomes under a defined treatment sequence. It does not provide a randomized comparison with chemotherapy alone. Even if a trial estimate were available, a difference from the historical benchmark would not by itself show that treatment caused the difference: patients, assessment, and clinical context may not be comparable. The registry record expressly identifies that the comparison is not randomized and that the arms are not like-for-like.

The endpoint is assessed among participants who completed neoadjuvant treatment and had nodal clearance evaluated at resection. It therefore describes a particular evaluable population, not necessarily every person enrolled or beginning treatment. The count of participants meeting this definition is not reported in the registry record. Nor are the endpoint estimate, its precision, missing-data handling, or the analysis population beyond this definition reported.

The listed secondary outcomes broaden the study questions to include radiographic and pathologic response, survival, adverse events, resection, and postoperative complications. Their presence in the registry does not indicate that results are available. The record reports 0 analyses and no secondary outcome results. The safety counts are descriptive registry entries and do not establish causation or provide a concurrent control comparison.

Accordingly, the record supports description of the treatment sequence, eligibility context, primary endpoint definition, stated historical objective, and recorded safety fields. It does not support a conclusion about whether the primary objective was achieved, the magnitude or precision of an endpoint result, or a causal treatment effect. Those conclusions would require reported outcome data and their analysis.

14. Why This Trial Matters Statistically

The statistical challenge in CHIO3 is not only estimating N2 nodal clearance, but defining exactly whose outcome contributes to that estimate. The registry limits primary-endpoint evaluability to patients who completed neoadjuvant therapy and had nodal clearance evaluated at resection. That makes the denominator central to interpretation. Without a reported evaluable count and outcome estimate, readers cannot assess either the observed percentage or its precision.

The study also illustrates the distinction between a historical benchmark and a concurrent control. The objective compares a target of 50% or greater with a historical rate of 30% for platinum doublet chemotherapy alone. That reference can frame a phase II question, but it does not have the design protections of a randomized contemporaneous comparison. The registry's single-group model means that a contrast with history would need cautious interpretation, even if an estimate were reported.

A further statistical issue is keeping the primary question distinct from the broader list of secondary outcomes. Response, survival, safety, resection, and complications each describe different aspects of the treatment course. Multiple endpoints can be informative, but their joint interpretation depends on prespecified methods and appropriate handling of multiplicity. Such methods are not reported in the registry record.

These features make transparent reporting especially important: the number evaluable, outcome estimate, uncertainty interval, handling of participants without an assessment, and analysis plan would all inform interpretation. The registry record does not report these details. Its design and objective are clear, but the available record does not provide the analyses needed to judge the primary statistical question.

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 design is single-group, with no concurrent comparator. The historical 30% reference does not ensure a like-for-like comparison with the trial population. The registry record itself notes that the comparison is not randomized and that arms are not a like-for-like control comparison. Therefore, the design cannot separate a difference from history from differences in population, care, or assessment.

The primary endpoint applies only to patients who completed neoadjuvant therapy and had nodal clearance evaluated at resection. The registry record does not report how many participants met that definition, what happened to participants without an assessment, or whether a separate population was analyzed. This limits assessment of potential selection related to evaluability.

No observed primary endpoint result, confidence interval, or analysis is reported in the registry record. The record indicates 0 analyses. It also does not report the statistical analysis plan, missing-data procedures, multiplicity handling, interim analyses, or outcome-specific inferential methods. The listed secondary outcomes therefore cannot be interpreted as evidence of observed effects.

The safety fields are divided by amendment period, but the record does not explain the amendment's substantive changes or provide a randomized comparison between those periods. The recorded counts should not be used to infer that amendment timing caused differences. The registry record also does not provide the event-level detail or causal assessment needed to attribute adverse events to a particular component of the treatment sequence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CHIO3 Trial: CHemotherapy Combined With Immune Checkpoint Inhibitor for Operable Stage IIIA/B Non-Small Cell Lung Cancer — NCT04062708.
• Registry record last updated 2026-09-23; status last verified 2026-07.
• Results first posted 2026-09-23.
• 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

CHIO3 is a phase II, open-label, single-group trial registered for potentially resectable stage IIIA/B non-small cell lung cancer with N2 disease. Enrollment is 38, and registry status is active, not recruiting. The treatment sequence is neoadjuvant platinum doublet chemotherapy plus durvalumab, followed by surgery, postoperative radiation, and adjuvant durvalumab for 13 cycles.

The primary endpoint is N2 nodal clearance among patients who completed neoadjuvant therapy and had nodal clearance assessed at resection. The objective is 50% or greater, with a historical 30% rate for chemotherapy alone as reference. The registry record does not report an observed primary endpoint result or analysis. It lists secondary outcomes covering response, survival, safety, resection, and postoperative complications, and records adverse-event counts by amendment period. No statistical plan, missing-data approach, or multiplicity procedure is reported in the registry record.