Nivolumab, Ipilimumab, and Short-course Radiotherapy in Adults With Newly Diagnosed, MGMT Unmethylated Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nivolumab, Ipilimumab, and Short-course Radiotherapy in Adults With Newly Diagnosed, MGMT Unmethylated Glioblastoma (NCT03367715), a na phase 2 study. The primary outcome is 1-year Overall Survival (OS).

2. Clinical Question

The clinical question is therefore descriptive: what one-year survival was observed among participants enrolled in this single-arm study? Without a comparator, the study cannot directly estimate how outcomes would differ under another treatment. Its design also does not separate the contribution of nivolumab, ipilimumab, or radiotherapy from the combined regimen.

3. Trial Design

This was a phase II, open-label, single-group trial sponsored by NYU Langone Health. The registry records enrollment of 10 and a completed status. The recorded start date is 2018-02-07, and the primary completion date is 2021-05-20. These dates describe the registry record; they do not supply an outcome follow-up schedule beyond the primary endpoint's 1-year timeframe.

Participants were adults with newly diagnosed, MGMT-unmethylated glioblastoma. The single treatment group received nivolumab, ipilimumab, and short-course radiation therapy. The arm description specifies that participants would initiate treatment on Day 1 within 6 weeks of their first diagnostic surgery for glioblastoma. Further details about treatment doses, schedules, eligibility criteria, and changes to treatment are not reported in the registry record.

Open-label means that treatment masking was not used. Allocation is recorded as not applicable, consistent with a single-group design rather than random assignment between study arms. As a result, the trial has no concurrent control group for separating treatment-associated outcomes from the course of disease, other care, or participant characteristics.

The primary outcome was one-year overall survival. Median overall survival and median progression-free survival are listed as secondary outcomes. Although the registry lists three outcome measures, it records no analyses, and outcome estimates are not reported in the registry record. The design and endpoint definitions can therefore be described, but the posted information does not establish what survival or progression-free survival was observed.

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 1-year Overall Survival (OS), measured over 1 year.

The primary endpoint is 1-year overall survival, expressed as a percentage of participants. The registry defines survival as the percentage alive at 1 year, measured from either the date of diagnosis or the start of treatment. It does not clarify which of those starting points was used for the reported endpoint, and no endpoint estimate is reported in the registry record.

Overall survival is a time-to-event outcome: the event is death, and the outcome concerns how long participants remain alive from a specified starting point. Reporting survival at a particular time provides a clinically interpretable snapshot of the survival experience by that time. A percentage alone, however, does not describe the full timing of deaths or the precision of the estimate. Interpretation also depends on clear definitions of the time origin, follow-up, and handling of participants whose status is unknown at the assessment point.

The registry also lists median overall survival and median progression-free survival as secondary outcomes. Their estimates and analysis details are not reported in the registry record. The primary endpoint's definition explains what the trial intended to measure, but it does not show the value observed or how precisely it was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A single-arm study estimates outcomes within a group receiving the study regimen. In this trial, the registry describes one group treated with nivolumab, ipilimumab, and short-course radiation therapy. There is no randomized comparator. The natural statistical focus is therefore a descriptive estimate, such as the percentage alive at the stated one-year assessment, rather than a randomized between-group treatment contrast.

For a binary outcome such as being alive at a specified time, the observed percentage is based on the number meeting the outcome definition relative to the number assessed under the analysis rules. Its uncertainty depends on the amount of information and on how outcomes and incomplete follow-up are handled. No one-year survival count, percentage, confidence interval, or analysis population is reported in the registry record. The survival estimate therefore cannot be reconstructed from the registry information.

Overall survival is usually understood through time-to-event methods because participants may have different lengths of follow-up. Such methods use the timing of events and account for participants who have not had the event by the end of observed follow-up, subject to assumptions about censoring. The registry defines a one-year survival percentage but does not report the method used to estimate it, the follow-up distribution, censoring details, or the starting point applied in the analysis. These elements are not reported in the registry record.

A confidence interval expresses uncertainty around an estimate under a specified statistical model. A narrow interval generally indicates greater precision than a wide interval, but precision is not the same as freedom from bias. In a small single-arm study, even a precisely calculated estimate would remain a description of the enrolled group rather than a randomized comparison. No confidence interval or other uncertainty measure for the primary endpoint is reported in the registry record.

The registry lists median overall survival and median progression-free survival as secondary outcomes. A median time-to-event outcome is the time by which half of the relevant population has experienced the event, under the chosen analysis method. Progression-free survival also requires a definition of progression and rules for assessing it. The registry record does not give the results, detailed definitions, or analysis methods for these secondary outcomes. Neither the medians nor their precision can be interpreted from the posted record.

There are no statistical analyses recorded in the registry. That does not establish why analyses are absent or whether analyses were conducted elsewhere. It means the registry record does not report the analysis procedures or results needed to assess endpoint estimation, model assumptions, or uncertainty. A statistical plan, including any adjustment strategy, interim analyses, or sample-size justification, is not reported in the registry record.

Planning calculations are conceptually different from observed results. A planning illustration estimates the sample size or event information that a hypothetical study might need under stated assumptions; it does not show what happened in the trial and is not observed power. The registry's stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. It distinguishes total events for time-to-event calculations from participants per arm for other calculations. Those assumptions describe a hypothetical planning exercise, not this single-arm trial's design. The registry does not report the observed effect needed to interpret such an illustration.

In general, over-dispersion occurs when variability in data is greater than a statistical model expects; accounting for it can prevent uncertainty from being understated. The registry does not identify an over-dispersion model for these outcomes, and no such method should be assumed. More generally, analytic choices must follow the outcome structure and available data. Since the registry does not report its analyses, the methods used to produce any unreported endpoint results cannot be evaluated.

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 + Ipilimumab + Short-course Radiation Th")
n      <- c(10)
events <- c(8)
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 + Ipilimumab + Short-course Radiation Th  10  8  80.0  44.4  97.5  49.0  94.3  48.2  94.0

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome, 1-year overall survival, and lists median overall survival and median progression-free survival as secondary outcomes. Considering multiple outcomes raises a multiplicity question: if many outcomes or analyses are tested, the chance of at least one apparently notable result can increase. A prespecified hierarchy or adjustment can address some multiplicity concerns, while clearly labeling secondary or exploratory outcomes helps readers interpret them. The registry record does not report a multiplicity strategy, a statistical analysis plan, or analyses for these outcomes.

Missing outcome information also affects interpretation. The record does not describe whether any participants had incomplete follow-up, how missing status was handled, or which participants were included in each endpoint analysis. It does not report an analysis population definition or methods for handling censoring. These details are not reported in the registry record and should not be inferred from enrollment or completion status.

The absence of registered analyses means that readers cannot assess whether the analysis matched a prespecified plan, whether outcomes were analyzed as intended, or how uncertainty was calculated. This is distinct from evidence that the methods were inappropriate: the relevant methods are simply not reported in the registry record. The recorded completion status and the presence of endpoint definitions do not resolve these gaps.

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: alanine aminotransferase increased (60.0%), aspartate aminotransferase increased (40.0%), diarrhea (30.0%), dizziness (20.0%), generalized muscle weakness (20.0%).

The registry records serious adverse events affecting 7 of 10 participants at risk in the nivolumab, ipilimumab, and short-course radiation therapy group. Other adverse events affected 10 of 10 participants at risk. The record also lists 9 deaths. These figures are group-level counts; they should not be added together, since the record does not state that the categories are mutually exclusive or describe how events overlap.

The listed serious adverse event terms include alanine aminotransferase increased (60.0%), aspartate aminotransferase increased (40.0%), diarrhea (30.0%), dizziness (20.0%), generalized muscle weakness (20.0%), and headache (20.0%). The percentages are registry-reported. The record does not provide event timing, duration, severity grading details, recurrence, or participant-level overlap for these terms.

These safety figures describe events recorded in the study group; they do not establish that the regimen caused each event or death. With no comparator group, the registry record cannot provide a like-for-like estimate of excess risk. The period over which the adverse events and deaths were counted is not reported in the registry record.

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

The registry record documents a phase II, open-label, single-arm study in adults with newly diagnosed, MGMT-unmethylated glioblastoma. Its primary objective was one-year overall survival after treatment with nivolumab, ipilimumab, and short-course radiation therapy. It also identifies median overall survival and median progression-free survival as secondary outcomes. These details describe the study's question and structure, not the answers to those questions.

The posted record does not report the primary endpoint estimate, secondary outcome estimates, or statistical analyses. It therefore cannot establish the observed one-year survival percentage, the median survival times, or the precision of any outcome estimate. The trial's completed status does not fill in these missing results.

Because the study had no comparator arm, outcomes in the treated group cannot be directly contrasted with outcomes under another treatment within this trial. The design also cannot isolate the effect of any one component of the combined regimen. Even if outcome estimates were reported, a single-arm result would describe this enrolled group and would not by itself quantify a treatment difference.

The safety counts are also descriptive. They record adverse events and deaths among participants in the study group, but do not establish causation. Without details on event timing, overlap, and a comparator, the figures cannot be interpreted as comparative risks or as a complete account of the treatment's safety profile.

The appropriate statistical reading is limited but useful: the registry identifies a defined population, a combined treatment approach, and survival objectives, while leaving key outcome and analysis information unreported. Any stronger conclusion about efficacy, comparative benefit, or causal safety effects would go beyond what the registry record reports.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between a clinical objective and an answer supported by reported data. A registry may identify a primary endpoint and define how it is intended to be measured, but readers still need an observed estimate, uncertainty information, and analysis details to judge what the study found. In this record, one-year overall survival is specified, but its result is not reported.

The single-arm design also makes the target of inference important. Such a study can describe outcomes among participants receiving a regimen, but it does not create a randomized estimate of the difference from another treatment. That limitation is especially relevant when a treatment program has multiple components, as in this trial: an observed outcome cannot be attributed separately to nivolumab, ipilimumab, or radiotherapy based on the design alone.

Finally, the record highlights why registry status, outcome definitions, and analysis reporting answer different questions. Completion indicates the recorded study status; it does not supply missing outcome estimates. Safety counts can be informative descriptions, but without timing, overlap, and comparison details they do not establish causation or comparative risk. Clear outcome reporting and transparent analysis methods are necessary for readers to assess both the results and their uncertainty.

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 of the available record is that it does not report the primary endpoint result or analyses. No one-year survival estimate or uncertainty measure is recorded. The listed secondary outcomes, median overall survival and median progression-free survival, also have no reported results. The registry record therefore leaves the main clinical outcome question unanswered.

The single-arm, open-label design has no concurrent randomized comparator. Outcomes cannot be used to estimate a within-trial difference from another treatment, and the combined regimen does not allow the separate contribution of each intervention to be identified. Open-label status means masking was not used; how this affected assessment or care is not reported in the registry record.

Enrollment is recorded as 10, but the registry does not report the number included in each endpoint analysis, missing follow-up, censoring, or analysis-population rules. The primary endpoint definition permits measurement from diagnosis or treatment start, but the record does not clarify which time origin was applied. Treatment doses, detailed schedules, eligibility criteria, and endpoint analysis methods are also not reported in the registry record.

For safety, the record supplies group counts and selected event terms but does not report timing, duration, overlap among events, or a comparison group. The figures should therefore be read as recorded descriptive information rather than causal estimates. These gaps are specific to what the registry record reports and do not establish what information may exist outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nivolumab, Ipilimumab, and Short-course Radiotherapy in Adults With Newly Diagnosed, MGMT Unmethylated Glioblastoma — NCT03367715.
• Registry record last updated 2022-07-01; status last verified 2022-06.
• Results first posted 2022-07-01.
• 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

NCT03367715 is recorded as a completed phase II, open-label, single-arm trial sponsored by NYU Langone Health. It enrolled adults with newly diagnosed, MGMT-unmethylated glioblastoma and evaluated nivolumab, ipilimumab, and short-course radiation therapy. The primary objective was 1-year overall survival; median overall survival and median progression-free survival were listed as secondary outcomes.

The registry records enrollment of 10, a start date of 2018-02-07, and a primary completion date of 2021-05-20. It reports safety counts, including serious adverse events affecting 7 of 10 participants at risk and 9 deaths. It does not report the primary or secondary outcome estimates or any statistical analyses. With no comparator group, the design supports no direct randomized treatment comparison.