An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer (NCT05500092), a randomized phase 2 study. The primary outcome is Complete Pathological Response.

2. Clinical Question

The primary comparison concerns the number of participants meeting that pathological definition in each group. The posted results list 3 participants in the chemotherapy-and-nivolumab group and 4 in the group that also received SBRT. Those counts are presented with group sizes of 9 and 8, respectively. A count does not by itself establish whether an observed difference is larger than could plausibly arise from random variation, and the registry record does not provide an estimable two-arm comparison for this binary outcome.

The trial also lists major pathological response and event-free survival as secondary outcomes. Their presence broadens the outcomes of interest, but the primary question remains the complete pathological response count after neoadjuvant treatment and surgery. The record does not report a treatment-effect estimate with uncertainty for the primary comparison.

3. Trial Design

This is an open-label, randomized, parallel-group phase 2 study sponsored by Montefiore Medical Center. Participants are assigned to neoadjuvant nivolumab and platinum doublet chemotherapy, either alone or with sub-ablative SBRT. The registry lists enrollment as 17. The posted group sizes are 9 for nivolumab plus platinum doublet chemotherapy and 8 for that regimen with SBRT.

The chemotherapy-and-nivolumab regimen is described as 3 cycles every 3 weeks. In the SBRT group, radiation is intended near the conclusion of cycle 1, with delivery on three consecutive days. The registry lists the radiation intervention as 8gy x 3. The treatment is neoadjuvant: the primary outcome is assessed in relation to therapy before surgery and examination of the resected specimen.

The registry lists the study start as 2023-01-25 and primary completion as 2025-07-01. Its status is active, not recruiting. These registry entries describe the study record and do not establish that every listed outcome has a final analysis. The primary outcome timeframe is stated as the end of 3 cycles, at week 9, with each cycle defined as 3 weeks. Its description says complete pathological response is observed after neoadjuvant therapy and surgical resection.

There is no masking. Participants and study personnel therefore are not described as blinded to assigned treatment. The record does not report a detailed randomization procedure, allocation concealment method, or a fuller protocol for treatment delivery. It also does not report a statistical analysis plan or sample-size justification. These omissions limit what can be concluded about the intended conduct and analysis beyond the design characteristics stated in the registry.

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.

Before assignment: Among 38 operable/resectable patients diagnosed with the appropriate stage of non-small cell lung cancer (NSCLC) during study activation, 17 patients were enrolled.

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 Complete Pathological Response, measured over At the end of 3 cycles, at week 9. Each cycle is defined as 3 weeks.

The primary endpoint is complete pathological response, reported as a count of participants in each study group. The registry defines this response as the absence of tumor cells in the resected specimen on histopathological examination. The outcome therefore reflects examination of tissue after neoadjuvant therapy and surgical resection, rather than a measurement based only on imaging or symptoms.

Pathological response is used in this setting to describe what is found in the surgical specimen after treatment before surgery. A complete response is a specific, stringent category under the registry definition. The endpoint can provide information about tumor findings at resection, but it is not itself a direct measure of longer-term outcomes such as event-free survival. The record lists event-free survival and major pathological response as secondary outcomes.

The posted primary results give counts by group: 3 among 9 in the nivolumab-plus-chemotherapy group, and 4 among 8 in the group that also received SBRT. These counts describe the endpoint as recorded, but do not quantify the uncertainty around a comparison. No two-arm comparative estimate is reported as estimable in the registry record. The timeframe is described as the end of 3 cycles, at week 9, while the endpoint definition also specifies assessment after surgical resection. The record does not provide further detail to reconcile the timing of treatment completion with the timing of specimen assessment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either meets the registry definition of complete pathological response or does not. The posted values are counts of participants with the response, with group sizes also reported. For this kind of endpoint, a comparison may be expressed as a difference or ratio of response probabilities, or through another binary-outcome method. The registry record does not report an estimable two-arm comparison, so no such effect estimate should be inferred from the counts alone.

What do the group counts tell us?

Counts communicate how many participants in each group were recorded as having the outcome. The group sizes provide the context needed to understand those counts. A count is not a measure of precision: it does not show the range of effect sizes compatible with the data. In general, uncertainty can be summarized with a confidence interval. The registry record does not report a confidence interval for the primary between-group comparison.

With a binary outcome and small group sizes, standard approximations may perform poorly or produce unstable estimates. Exact methods or methods designed for sparse data can sometimes be considered in general, but the record does not state which comparative method was planned or used. It is not appropriate to select a method on the study's behalf or to present a new estimate as though it were the sponsor's result. No p-value for the primary comparison is reported in the registry record.

What does randomization contribute?

Random assignment is intended to make the treatment groups comparable, on average, with respect to factors known and unknown at assignment. In an individual trial, chance differences can still occur, and group sizes of 9 and 8 leave limited information for assessing balance or estimating effects precisely. The registry record does not report baseline characteristics in the registry record for this analysis. It also does not describe the randomization sequence, stratification, or allocation concealment, so those design details cannot be evaluated.

The study is open label, with no masking listed. Lack of masking may affect behavior, care, or outcome assessment in some settings. The primary endpoint is a pathological assessment of resected tissue, but the record does not say whether the pathologists assessing specimens were masked to treatment assignment. The endpoint's measurement process should therefore be understood from the stated definition, without assuming a particular blinding safeguard.

How should planning illustrations be read?

Planning illustrations use the observed effect as a reference and apply assumptions stated for the illustration: a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such calculations address the number of participants per arm that might be needed under those assumptions; they are not observed power and are not a report of the trial's original design calculations. The registry record does not report the trial's own sample-size justification or statistical plan. No planning values are repeated in this explanation.

In general, a planning calculation depends on the assumed effect, outcome variability, significance level, allocation, and chosen method. It should not be interpreted as evidence that the observed result is reliable or that a study had a particular probability of detecting an effect after the fact. Here, the calculation is explicitly a planning illustration based on the observed effect, not an account of the study's prespecified design.

What does the missing comparison imply?

The record states that values are missing or not estimable for a two-arm comparison of the binary endpoint. That means the posted counts do not come with a reported comparative statistic suitable for interpreting the strength and precision of evidence between arms. The reason for the missing or non-estimable result is not reported in the registry record. It is therefore not possible to determine whether the issue arose from the analysis method, data availability, or another cause.

The registry record reports no analyses in the analysis listing. That does not establish that no analyses were conducted; it means an analysis is not listed there. The record also does not report an analysis population, handling of missing endpoint values, or a prespecified approach to interim analyses. Those omissions matter because the way participants are included and missing outcomes are handled can affect a trial's estimate and its uncertainty.

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("Nivolumab + Platinum Doublet Chemotherapy", "Nivolumab + Platinum Doublet Chemotherapy + SBRT (")
n      <- c(9, 8)
events <- c(3, 4)
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  Nivolumab + Platinum Doublet Chemotherapy  9  3  33.3  7.5  70.1  12.1  64.6  12.2  65.2
ARM  Nivolumab + Platinum Doublet Chemotherapy + SBRT (  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists complete pathological response as the primary outcome and major pathological response and event-free survival as secondary outcomes. The registry entries summarized for this analysis do not include results for those secondary outcomes. The record does not report how testing across multiple outcomes was handled, whether a hierarchy was prespecified, or whether any adjustment for multiple comparisons was planned. Without that information, the role of multiplicity in interpreting any reported statistical tests cannot be assessed.

Missing data handling is not reported in the registry record. The primary result gives group sizes and response counts, but does not describe whether all randomized participants had evaluable surgical specimens, how participants without an evaluable specimen were classified, or whether any imputation was used. The record also does not state the analysis population, such as whether the primary outcome was analyzed according to randomized assignment or among a narrower set of participants.

No interim analysis plan or stopping rule is reported in the registry record. The listed analysis count is 0, which indicates no analysis is listed in that registry entry; it should not be interpreted as proof that no analyses took place. The statistical analysis plan, including any prespecified handling of missing values and multiple outcomes, is not reported in the registry record. These gaps limit assessment of how the posted counts were selected and analyzed.

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: syncope (12.5%), hematoma (12.5%), anemia (12.5%), pneumonia (11.1%), non-cardiac chest pain (11.1%).

The safety figures are participant counts reported separately for each treatment group. For serious adverse events, the record lists 1 affected participant among 9 at risk in the nivolumab-plus-chemotherapy group, and 1 among 8 at risk in the group that also received SBRT. The recorded death counts are 0 and 1, respectively. The registry figures do not establish whether a death was caused by treatment, and a causal attribution is not reported in the registry record.

For other adverse events, the record lists 9 affected participants among 9 at risk in the chemotherapy-and-nivolumab group and 6 among 8 at risk in the SBRT group. These are group-level counts and do not describe event severity, duration, recurrence, or clinical consequences. The precise definition used for the other-adverse-event category is not reported in the registry record.

The listed top serious adverse event terms include Syncope, Hematoma, and Anemia at 12.5% each, and Pneumonia, Non-cardiac Chest pain, and Dyspnea at 11.1% each. The record does not specify the denominators or arm attribution for these percentages in the registry record. They should not be interpreted as comparative risks between treatment groups. Small group sizes and the absence of additional event detail limit what these figures can establish about relative safety.

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

The complete pathological response results describe what was recorded in the resected specimens for participants in each treatment group. They show 3 responses among 9 participants assigned nivolumab plus platinum doublet chemotherapy, and 4 among 8 assigned the regimen with SBRT. The counts are relevant to the primary endpoint, but the registry record does not provide an estimable comparative analysis. They therefore do not quantify the uncertainty in the difference between groups.

The study addresses a focused question: whether adding SBRT to neoadjuvant nivolumab and platinum doublet chemotherapy is associated with a different complete pathological response count in this setting. Its randomized design is relevant to that question, but the posted endpoint counts alone are not enough to establish the size, precision, or statistical strength of any treatment effect. Nor do they establish that any observed difference is caused by the addition of SBRT.

The endpoint is pathological response after neoadjuvant treatment and surgical resection. It does not by itself establish longer-term outcomes. Event-free survival is listed as a secondary outcome, but its result is not included in the registry record for this analysis. Major pathological response is also listed as secondary, with no result. Conclusions about those outcomes cannot be drawn from the complete pathological response counts.

The data also do not determine how the regimens compare in terms of all adverse outcomes, treatment burden, or other clinical outcomes. The safety record gives counts, but not enough detail to establish event attribution or a comparative safety profile. Results from this small phase 2 study should be understood as findings in the enrolled trial population, rather than as a basis for conclusions about all people with resectable stage IIA to IIIB non-small cell lung cancer.

In short, the posted results document the observed primary endpoint counts and selected safety counts. They do not supply the comparative uncertainty estimates or broader outcome information needed to characterize the full treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically notable because it randomizes participants between a neoadjuvant regimen and the same regimen with SBRT added, while using a defined pathological endpoint. That structure gives the study a direct comparative question. The primary outcome is also expressed in an interpretable form: the number of participants whose resected specimen has no tumor cells on histopathological examination.

The posted group sizes are 9 and 8, and the complete pathological response counts are 3 and 4. With groups of this size, the observed counts offer limited information for estimating a stable comparative effect. A reported uncertainty interval would help readers judge the range of effects compatible with the data, but the registry record does not provide an estimable two-arm comparison for this endpoint. This absence is important: readers should not treat a difference in counts as a statistically established effect.

The study also illustrates the distinction between a trial's design and its available results. Randomization supports a planned comparison, but interpretation still depends on the analysis, endpoint completeness, handling of missing data, and prespecified statistical methods. Those details are not reported in the registry record. The registry lists secondary outcomes, but their results are not available in the registry record for this analysis.

The safety counts further show why statistical context matters. Counts of affected participants and event-term percentages can be informative, but their meaning depends on definitions, denominators, attribution, and follow-up. Some of that information is not reported in the registry record. For a small phase 2 study, careful distinction between descriptive findings and comparative evidence is central to sound interpretation.

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 outcome comparison is not reported as estimable in the registry record. Although counts and group sizes are listed, no comparative effect estimate, confidence interval, or p-value is included. This prevents assessment of the precision of the between-group result from the posted primary data.

The registry record does not report the statistical analysis plan, sample-size justification, analysis population, missing-data approach, or use of interim analyses. It also does not explain why the comparison is missing or not estimable. These limitations make it difficult to determine how the posted counts relate to the intended analysis or whether outcome data were unavailable for some participants.

The design is open label, and masking of pathological assessors is not reported. Baseline characteristics and details of randomization and allocation concealment are also not reported in the registry record. Such omissions limit assessment of group comparability and possible influences on outcome measurement.

Only the primary endpoint counts and selected safety counts are included in the registry record for this analysis. Results for the listed secondary outcomes, major pathological response and event-free survival, are not included. Safety information lacks details on event attribution and the denominators or group assignment for the listed serious adverse event term percentages. The stated primary timeframe refers to the end of 3 cycles, at week 9, while the endpoint definition refers to assessment after surgical resection; additional timing detail is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer — NCT05500092.
• Registry record last updated 2026-10-06; status last verified 2026-10.
• Results first posted 2026-08-27.
• 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

NCT05500092 is an open-label, randomized, parallel-group phase 2 study sponsored by Montefiore Medical Center. It compares neoadjuvant nivolumab and platinum doublet chemotherapy with the same treatment plus SBRT (8gy x 3) for resectable stage IIA to IIIB non-small cell lung cancer. The registry lists enrollment as 17, with posted group sizes of 9 and 8.

The primary outcome is complete pathological response after neoadjuvant therapy and surgical resection. The posted counts are 3 in the chemotherapy-and-nivolumab group and 4 in the group that also received SBRT. The registry record does not provide an estimable two-arm comparison. Major pathological response and event-free survival are listed as secondary outcomes.

The record lists the study as active, not recruiting, with a start date of 2023-01-25 and primary completion date of 2025-07-01. It does not report the statistical analysis plan, missing-data handling, or a sample-size justification.