An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) (NCT02617589), a randomized phase 3 study. The primary outcome is Overall Survival (OS).

2. Clinical Question

The trial record describes a comparison of two treatment strategies, each paired with radiation therapy, in a specified glioblastoma population. The main statistical question concerns time to death from any cause, rather than a single observation at a fixed follow-up visit. The posted comparison uses a hazard ratio from a stratified Cox proportional hazard model and a stratified log-rank test. Those methods compare survival experience over follow-up while accounting for censoring, rather than comparing only the reported median survival times.

The registry record lists progression-free survival, survival at 24 months, and outcomes in a tumor mutational burden high population among the secondary outcomes. Results are available for some secondary outcomes, but results for the tumor mutational burden high outcomes are not reported in the registry record. The trial’s status is completed, and its recorded enrollment is 560.

3. Trial Design

This was a randomized, phase 3, open-label study with a parallel-group design. The registry record lists Bristol-Myers Squibb as the sponsor and describes adults with newly diagnosed glioblastoma whose tumors were MGMT-unmethylated. Allocation was randomized, and masking was listed as none, so the study was not blinded according to the registry record. The recorded enrollment was 560.

One group received nivolumab with radiation therapy; the other received temozolomide with radiation therapy. The record describes nivolumab as being given every two weeks and then every four weeks. Temozolomide is described as standard therapy in combination with radiation. The specific radiation dose is not reported in the registry record.

The primary outcome was overall survival, defined as time from randomization to death from any cause, with participants not known to have died censored at their last known alive date. The primary outcome timeframe was up to 3 years. The primary analysis population was all randomized participants. The registry record lists progression-free survival and survival at 24 months among the secondary outcomes, along with outcomes in a tumor mutational burden high population.

The recorded study start was 2016-03-01, and primary completion was 2019-01-17. The study status is completed. Further details about the original sample-size justification, planned interim analyses, and the full statistical analysis plan are not reported in the registry record. Those omissions limit what can be concluded about the trial’s original planning choices or about analyses beyond the ones 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.

Randomization

Reasons for not completing this period:

Treatment

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All Randomized Participants: All enrolled Participants who were randomized to any treatment arm.

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.

Population: Baseline characteristics were summarized using all randomized subjects (all enrolled subjects who were randomized to any treatment arm)

6. Primary Endpoint

The registry lists the primary outcome as Overall Survival (OS), measured over up to 3 years.

Overall survival measures the time from randomization until death from any cause. A participant who had not died by the last known alive date was censored at that date. This endpoint captures survival over follow-up without restricting the event to a particular cause of death. The registry record specifies a timeframe of up to 3 years and defines the primary population as all randomized participants assigned to any treatment arm.

Time-to-event outcomes are useful when participants can have different lengths of follow-up or when some have not experienced the event by the time their outcome is assessed. Censoring allows their observed follow-up to contribute information up to the last date they were known to be alive, rather than treating them as if a death had occurred. In general, this approach relies on appropriate handling of censoring and follow-up; further details of those procedures are not reported in the registry record.

The posted primary summaries include median overall survival for each group and a hazard ratio for the comparison. A median describes the time by which the estimated survival experience reaches its midpoint. It does not describe every participant’s outcome or capture the whole survival pattern. The hazard ratio compares event rates over follow-up under the model used for the analysis, so it addresses a different aspect of the data than the medians. The confidence intervals indicate the statistical uncertainty around the reported estimates.

7. Results Posted in the Registry

• Nivolumab + Radiation Therapy vs Temozolomide + Radiation Therapy: hazard ratio 1.31 (95% CI 1.09–1.58), reported p = 0.004 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Kaplan-Meier Plot of Progression Free Survival

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log-rank test stratified); it was not recalculated.
• Result:
  • Nivolumab + Radiation Therapy vs Temozolomide + Radiation Therapy: hazard ratio 1.43 (95% CI 1.19–1.71) (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically higher for Nivolumab + Radiation Therapy vs Temozolomide + Radiation Therapy than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Overall Survival Rate at 24 Months

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Temozolomide + Radiation Therapy: 21.1% (59/280) versus 10.7% (30/280) on control; risk difference 10.4 percentage points (95% CI 4.4 to 16.4), risk ratio 1.97 (1.31–2.95); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Temozolomide + Radiation Therapy than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the secondary results with posted estimates, the broad pattern is consistent with the primary overall survival comparison: the reported estimates do not point toward a more favorable observed outcome for the nivolumab-plus-radiation group. This consistency can add context, but secondary endpoints address different questions and should not be treated as independent confirmation of the primary result.

Progression-free survival concerns progression or death and therefore reflects a different event definition from overall survival. Survival at 24 months focuses on status at a fixed follow-up time. These outcomes are related to overall survival, but they do not measure the same thing. Differences in endpoint definition, follow-up, and statistical method mean that one endpoint’s estimate cannot simply be substituted for another’s.

The registry record lists outcomes in the tumor mutational burden high population as secondary outcomes, but their results are not reported in the registry record. The available information therefore does not support conclusions about those subgroup outcomes. The record also does not report a multiplicity procedure or a hierarchy controlling interpretation across secondary outcomes. When several outcomes are examined, unadjusted findings carry less weight because the chance of at least one apparently notable result can increase as more comparisons are made. The secondary results are best viewed as supportive context, not as a replacement for the primary analysis or as definitive evidence on their own.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Kaplan-Meier Plot of Progression Free Survival
• Overall Survival Rate at 24 Months
• Overall Survival in Tumor Mutational Burden (TMB) High Population
• Progression Free Survival in Tumor Mutational Burden (TMB) High Population

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a time-to-event measure. Each participant contributes follow-up from randomization until death or, if death was not observed, until the last known alive date. The latter observation is censored. In general, censoring is not the same as having no event ever; it means the event time is not known beyond the end of observed follow-up. Survival methods use the observed time and censoring information to estimate the outcome over time.

What does the median describe?

The reported median is the estimated time at which the survival curve reaches its midpoint. It is a compact description of a time-to-event distribution, but it leaves out information about the shape of the curve and the timing of events across the rest of follow-up. Two groups can have similar medians while differing elsewhere in their survival patterns, or the converse. A median alone does not show whether the difference is consistent across follow-up.

What does the hazard ratio describe?

The registry record reports a hazard ratio from a stratified Cox proportional hazard model. In general, a hazard is the instantaneous event rate among participants who remain at risk at a given time. A hazard ratio compares those rates between groups under the model. It is not a ratio of medians, an absolute difference in survival probability, or a statement about the probability that a particular participant will experience the event. The comparison order matters when interpreting a value above or below 1; the posted primary comparison is nivolumab plus radiation therapy versus temozolomide plus radiation therapy.

The Cox model is called proportional hazards because its usual interpretation assumes that the relative hazard between groups is stable over time. If that assumption does not hold, a single hazard ratio may not fully describe the changing relationship. The registry record does not report whether proportional hazards were assessed, what diagnostics were used, or whether alternative analyses were planned.

Why use a stratified log-rank test?

The reported method is a log-rank test stratified across specified groups or factors. In general, the log-rank test compares survival experience over observed follow-up while taking account of the timing of events and censoring. Stratification allows the comparison to be carried out within strata and then combined. The factors used for stratification are not reported in the registry record, so their role cannot be examined from the posted information.

The reported primary p-value is 0.004. A p-value describes how compatible the observed test result is with a null hypothesis under the test’s assumptions; it is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The confidence interval supplies complementary information about the range of effect values compatible with the model and observed data at its stated confidence level.

How do the secondary analyses differ?

Progression-free survival is also a time-to-event outcome. Its registry definition is time from randomization to documented tumor progression or death from any cause. The posted comparison uses a stratified Cox proportional hazard model and stratified log-rank test. The registry record does not report a p-value for this comparison. For survival at 24 months, the measure is a percentage at a fixed time rather than a time-to-event summary. An unadjusted recalculation is posted for the binary comparison, including p < 0.001; no sponsor-reported analysis for that outcome is listed.

In general, time-to-event analyses can use information from differing follow-up durations, while a fixed-time percentage focuses on status at a chosen time point. They answer related but not identical questions. Comparisons across several outcomes also raise the possibility of chance findings when many tests are considered. The registry record does not report how multiplicity was handled or whether a prespecified hierarchy governed the secondary analyses.

Further model details, including covariates beyond stratification, missing-data procedures for secondary outcomes, and sensitivity analyses, are not reported in the registry record. Consequently, the posted results support interpretation of the named analyses, but do not allow a full audit of every modeling choice or assumption.

11. Confidence Intervals and Precision

The 95% confidence intervals communicate uncertainty in the reported estimates. In general, a confidence interval is a range produced by a statistical procedure that, under repeated use of the same method and its assumptions, would cover the target value at the stated rate. It is not a range containing a known proportion of individual participant outcomes, and it does not assign a probability to the true effect after the data have been observed.

For median overall survival, the interval is 12.62 to 14.29 months for nivolumab plus radiation therapy and 13.27 to 16.13 months for temozolomide plus radiation therapy. For the primary hazard ratio, the interval is 1.09 to 1.58. The hazard-ratio interval does not include 1, which is the value representing equal hazards under the model. The interval still allows a range of possible relative effects, so the point estimate should not be treated as exact.

Confidence intervals for the secondary outcomes also reflect uncertainty. Their interpretation depends on the method used to construct them and on the analysis assumptions. For fixed-time percentages, an interval describes uncertainty in the estimated percentage; for time-to-event estimates, the analysis accounts for event timing and censoring. The registry record does not provide all the methodological detail needed to independently assess those intervals.

Precision is distinct from statistical significance. A narrow interval generally indicates more precision than a wide one, but precision alone does not determine whether an outcome is important. The interpretation should consider the estimate, its interval, the endpoint definition, and the study context together. The registry record does not report a clinically important threshold for the primary endpoint, so the posted statistical estimates alone cannot establish the clinical importance of a particular difference.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial’s original design assumptions. The registry record does not report the original sample-size justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect.

For time-to-event outcomes, the figures represent total events needed across the comparison, using the Schoenfeld approach. They are not participant counts per arm. For the fixed-time binary outcome, the figures are participants per arm. The distinction matters: an event target for a survival analysis is not interchangeable with a target number of participants, because participants may have different follow-up and not all will experience the event during the observation period.

The 80% power column describes the planning number of events or participants that, under the stated assumptions and effect size, would give an 80% chance of rejecting the null hypothesis if the assumed effect were the true effect. The 90% power column describes the corresponding planning target for a 90% chance. These are design probabilities under a model, not guarantees that a future study will produce a particular result.

The rows that plan for smaller fractions of the observed effect require more events or participants than rows based on the full observed effect. This is expected in general: smaller differences are harder to distinguish from random variation and therefore require more information. These sample-size illustrations are not observed power. They do not measure the probability that the completed trial was successful or establish whether its original design was adequate.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.310, so ln(HR) = 0.2700.
2. d = 4 × (1.96 + 0.842)² / [ln(1.310)]² = 430.6, rounded up to 431 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.31                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(2617589)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 431 (80% power), 577 (90% power)
 75% of observed effect: events = 766 (80% power), 1,025 (90% power)
 50% of observed effect: events = 1,723 (80% power), 2,306 (90% power)
Simulated power with 431 events: 0.806 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The primary hazard ratio, confidence interval, p-value, and named analysis method are reported in the sponsor analysis in the registry record. The posted primary estimate is 1.31, with a 95% confidence interval from 1.09 to 1.58 and p = 0.004; the method is a stratified Cox proportional hazard model with a stratified log-rank test. The record does not flag a discrepancy between the posted primary result and the sponsor’s analysis.

For this time-to-event outcome, the interpretation therefore rests on the sponsor-reported hazard ratio rather than a recalculation from group medians. Medians and their confidence intervals do not contain the event-time information required to reconstruct the sponsor’s model-based comparison. The sponsor’s reported analysis is the relevant result for the primary comparison.

The 24-month survival comparison is different: the registry record lists an unadjusted recalculation but does not list a sponsor-reported analysis for that outcome. Its p-value should therefore be read as an unadjusted recalculation from posted summary information, not as a sponsor-reported inferential result. The registry record does not give enough detail to determine whether that analysis matches any fuller prespecified sponsor analysis outside the posted results.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and several secondary outcomes, including progression-free survival, survival at 24 months, and outcomes in a tumor mutational burden high population. It does not report whether the investigators adjusted for multiple comparisons, used a prespecified testing hierarchy, or designated which secondary analyses were confirmatory. This matters because repeated testing across outcomes can increase the chance of a nominally notable result arising by chance.

The reported primary p-value belongs to the named primary comparison and its stated analysis. The registry record does not say whether that p-value was adjusted for any other testing. The 24-month survival comparison is an unadjusted recalculation, and no sponsor-reported analysis is listed for it. The progression-free survival comparison has no p-value reported. Results for the listed tumor mutational burden high outcomes are not reported in the registry record.

The primary analysis population is all randomized participants. The primary outcome definition specifies censoring participants who had not died at their last known alive date. This gives a stated approach for that endpoint, but broader details about missing data, loss to follow-up, or sensitivity analyses are not reported in the registry record. The record does not describe how missing outcome information was handled for the secondary outcomes.

Interim analyses, stopping boundaries, and the full statistical analysis plan are also not reported in the registry record. Their absence from the posted information means it is not possible to assess whether interim monitoring affected the final testing procedure or how all planned analyses were controlled. These reporting gaps do not change the stated estimates; they limit assessment of the complete analysis strategy and the strength of confirmatory claims beyond the primary result.

16. 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: malignant neoplasm progression (32.0%), seizure (13.3%), tumour flare (5.4%), epilepsy (4.0%), headache (4.0%).

The registry record lists serious adverse-event figures for the two groups. In the nivolumab plus radiation therapy group, 206 participants were reported with serious adverse events among 278 at risk; in the temozolomide plus radiation therapy group, 141 were reported among 275 at risk. The record also lists deaths of 269 and 253, respectively, in the adverse-event information. These figures should be read with their stated group-specific risk counts, not as estimates of a treatment effect on their own.

The serious-event terms listed most prominently include malignant neoplasm progression at 32.0%, seizure at 13.3%, and tumour flare at 5.4% for the reported serious-event listing. Other listed terms include epilepsy, headache, and pulmonary embolism. The registry record does not provide enough detail to determine attribution, timing, duration, or whether an event was considered related to study treatment. It also does not describe the full event-coding and collection procedures.

Serious adverse-event counts do not by themselves establish comparative safety. Group differences can be affected by follow-up and exposure, and the record does not provide all the information needed to interpret those factors. These data describe reported events; they do not establish causation.

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

The primary result is a comparison of overall survival between randomized groups of adults with newly diagnosed, MGMT-unmethylated glioblastoma receiving radiation therapy with either nivolumab or temozolomide. The sponsor-reported hazard ratio is 1.31 for nivolumab plus radiation therapy versus temozolomide plus radiation therapy, with a 95% confidence interval from 1.09 to 1.58 and p = 0.004. Under the reported model, this estimate indicates a higher event hazard in the first group during follow-up.

This is a group-level statistical result. It does not determine an individual participant’s outcome, explain the biological reasons for the observed difference, or establish how the results apply to people who do not match the study population. The posted summaries do not report all details about study conduct, adherence, subsequent treatment, or model checking that could inform a broader interpretation.

The result also does not mean that every participant in one group experienced an earlier event than every participant in the other. Survival distributions overlap, and the confidence interval expresses uncertainty around the estimated relative hazard. The reported median values describe the midpoint of estimated survival experience, while the hazard ratio summarizes the modeled relative event hazard over follow-up; neither should be interpreted as a complete description of each participant’s course.

Secondary results add context but have distinct definitions and limitations. The record does not report multiplicity adjustment, and results for the listed tumor mutational burden high outcomes are not reported in the registry record. The findings should therefore be understood as the posted results for this randomized comparison, rather than as a universal claim about all patients with glioblastoma or all treatment settings.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares two treatment strategies through random allocation and evaluates a time-to-event primary outcome. Randomization is designed to support a fair comparison of groups by reducing systematic differences at allocation, although the registry record does not provide enough information to assess every aspect of trial conduct. The open-label design means treatment assignment was not masked, a feature that can matter for outcomes or decisions influenced by knowledge of treatment, even though overall survival is a relatively direct endpoint.

The primary comparison uses both a stratified log-rank test and a stratified Cox proportional hazard model. Those methods incorporate event timing and censoring rather than reducing the analysis to a single follow-up snapshot. The confidence interval makes the uncertainty around the estimated hazard ratio visible, complementing the reported p-value.

The record also illustrates why outcome definitions and analysis plans matter. Overall survival, progression-free survival, and survival at a fixed time answer related but distinct questions. Secondary outcomes can help describe the pattern of findings, but without reported multiplicity procedures or complete analysis details, their statistical weight is more limited. Results for the listed tumor mutational burden high outcomes are absent from the registry record.

Finally, the posted planning illustrations are based on observed effects and should not be confused with the trial’s original design justification. The registry record does not report that original justification. Separating planning illustrations from trial results helps prevent retrospective calculations from being mistaken for evidence about the probability that the completed study was adequately powered.

19. 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 registry record does not report the full statistical analysis plan, the original sample-size justification, interim analyses, or the factors used for stratification. It also does not state whether proportional hazards were assessed or describe sensitivity analyses. These omissions make it difficult to evaluate the complete prespecification and robustness of the primary model.

The study was open label, with masking listed as none. Knowledge of assigned treatment can influence some aspects of care, reporting, and assessment, although the primary endpoint is death from any cause. The registry record does not describe whether outcome assessment or other trial procedures included protections against such influences.

Several secondary outcomes are listed, but the record does not report a multiplicity adjustment or an analysis hierarchy. Results for the tumor mutational burden high outcomes are not reported in the registry record. The progression-free survival comparison has no reported p-value, and no sponsor-reported analysis is listed for the 24-month survival comparison. These reporting gaps limit the strength of conclusions that can be drawn from secondary findings.

Information about missing data beyond the primary endpoint’s stated censoring definition, follow-up completeness, treatment adherence, and post-progression care is not reported in the registry record. The record also does not provide enough detail to interpret serious adverse-event attribution and exposure. These limits concern the available reporting and do not, by themselves, establish that the trial procedures were inadequate.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) — NCT02617589.
• Registry record last updated 2023-03-28; status last verified 2023-03.
• Results first posted 2021-02-03.
• 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.

23. Record Summary

NCT02617589 is a completed, randomized, open-label, parallel-group phase 3 study sponsored by Bristol-Myers Squibb. It enrolled adults with newly diagnosed, MGMT-unmethylated glioblastoma and compared nivolumab plus radiation therapy with temozolomide plus radiation therapy. Recorded enrollment was 560.

The primary outcome was overall survival, defined from randomization to death from any cause, with censoring at the last known alive date for participants not known to have died. The sponsor-reported hazard ratio was 1.31, with a 95% confidence interval from 1.09 to 1.58 and p = 0.004, using a stratified Cox proportional hazard model and stratified log-rank test.

Secondary outcomes include progression-free survival and survival at 24 months. The registry record does not report results for the listed tumor mutational burden high outcomes. Details of the original sample-size justification, multiplicity procedures, and full analysis plan are not reported in the registry record.