M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC) (NCT03840902), a randomized phase 2 study. The primary outcome is Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator.

2. Clinical Question

The registry describes a randomized, double-blind, controlled study in unresectable Stage III non-small cell lung cancer. Its primary outcome was progression-free survival assessed by investigators using RECIST version 1.1. The posted median was 3.7 months in each group. The registry also includes objective response rate results and adverse-event counts, but it does not post a sponsor-reported hazard ratio or a formal analysis comparing the primary outcome between groups.

The comparison concerns complete treatment strategies, not M7824 or durvalumab in isolation: both groups received concurrent chemoradiation, while the assigned accompanying and subsequent therapies differed. The registry record does not report enough detail to establish the clinical rationale for each treatment component or the criteria used to choose among the listed chemotherapy regimens.

3. Trial Design

This was a Phase 2, randomized, parallel-group, triple-masked study. The official title describes it as multicenter, double blind, and controlled. The registry lists 153 participants enrolled. The posted primary analysis population was the Full Analysis Set, including participants randomized to study treatment.

One group received concurrent chemoradiation with M7824, followed by M7824. The chemotherapy options were cisplatin with etoposide, carboplatin with paclitaxel, or cisplatin with pemetrexed; each was given with intensity-modulated radiation therapy. The comparator group received the same listed chemoradiation options with placebo matched to M7824, followed by durvalumab. The registry does not report how participants were assigned among the chemotherapy options.

The posted arm sizes for the primary endpoint were 75 participants in the M7824 sequence and 78 in the placebo-then-durvalumab sequence. These are the endpoint-specific counts, not a statement about the intended allocation ratio. The primary outcome was investigator-assessed progression-free survival. Its stated timeframe was from randomization to progression or death, assessed approximately up to 27 months.

The study began on 2019-04-16, had a primary completion date of 2023-02-17, and is listed as terminated. The reason for termination and the timing or circumstances of the decision are not reported in the registry record. The registry record also does not report the intended treatment duration, detailed visit schedule, randomization method, allocation concealment procedures, or masking arrangements for each study role. These details should not be inferred from the general design labels.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included all participants who were randomized to study treatment.

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: Full Analysis Set (FAS) included all participants who were randomized to study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator, measured over Time from randomization to the date of first documentation of PD or death, assessed approximately up to 27 months.

Progression-free survival (PFS) measures the time from randomization until the first documented disease progression or death from any cause, whichever occurs first. In this trial, investigators assessed progression using RECIST version 1.1. The registry definition describes progression as at least a 20% increase in the sum of the longest diameters, using the smallest recorded sum since baseline as the reference, or the appearance of one or more new lesions.

PFS is a time-to-event endpoint: it uses both whether an event occurred and the time at which it occurred. The median PFS is the time by which half of the analyzed group has experienced progression or death, under the assumptions of the time-to-event analysis. It is not the average survival time and does not describe every participant’s course. The registry says PFS was analyzed with the Kaplan-Meier method.

For this trial, the posted median was 3.7 months in each group. The endpoint is useful for describing how long participants remain alive without documented progression, but a pair of medians alone does not describe the full survival curves or quantify the relative rate of events between groups. The registry record does not report a sponsor-reported hazard ratio, confidence interval for a treatment comparison, or test of the primary endpoint. The median values therefore support a descriptive reading, not a complete comparative inference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Progression-free survival is a time-to-event outcome. Participants may have different follow-up times, and some may not have had a documented event by the end of their observed follow-up. Kaplan-Meier estimation is a general statistical method for describing event-free probability over time while accounting for differing follow-up and censoring. In general, censoring means that an event time is not observed during a participant’s available follow-up; the method uses the observed time without treating it as an event time. The registry says Kaplan-Meier was used, but detailed censoring rules and the handling of missing or incomplete assessments are not reported in the registry record.

What does a median PFS describe?

The median is the time at which the estimated event-free probability reaches its midpoint. It compresses a time-to-event distribution into one value, so it cannot show the entire curve or how event timing differs across follow-up. The posted medians are 3.7 months in both groups. The primary outcome lists dispersion as a full range, with limits of 1.9 to 5.6 months for the M7824 sequence and 1.8 to 3.9 months for the placebo-then-durvalumab sequence. A range is not a confidence interval for a median. Confidence intervals instead express statistical uncertainty about an estimated quantity under a specified method.

Why is a comparative estimate important?

A randomized comparison is usually interpreted using an estimate of the between-group contrast and its uncertainty, not by comparing two arm summaries alone. For time-to-event outcomes, a hazard ratio is one common relative measure, while a difference between survival probabilities at a specified time is another possible summary. General interpretation of either requires knowing the estimate, its confidence interval, and the analysis assumptions. The registry record does not report a sponsor-reported hazard ratio or another formal primary comparison. The label stating that the outcome was analyzed by Kaplan-Meier does not, by itself, provide those missing comparative results.

In general, over-dispersion matters when a statistical model assumes more uniform variability than the data exhibit. If variation is greater than the model allows, standard errors and confidence intervals may be too optimistic unless the model accounts for that extra variation. The registry does not state that an over-dispersion model was used or describe a model-based primary comparison, so no such model should be presumed for these results.

How should the response-rate comparison be read?

Objective response rate is a binary outcome: each participant is classified according to whether an objective response was recorded under the stated criteria. The posted response rates are 29.3% and 32.1%, with arm-specific 95% confidence intervals of 19.4% to 41.0% and 21.9% to 43.6%. A confidence interval conveys the uncertainty associated with an estimate under its statistical method; it is not a guarantee that the true value lies within the interval. The registry lists no reported sponsor analysis for this outcome.

A simple unadjusted recalculation from the posted summary statistics gives p = 0.716. This is not a sponsor-reported analysis. It is unadjusted, so it does not address multiplicity from assessing several outcomes, nor does it incorporate an adjustment that may have been prespecified but is not reported in the registry record. The recalculated result is compatible with uncertainty about the direction and size of a response-rate difference; it does not prove no difference.

What do the planning illustrations mean?

The posted planning illustrations are calculations based on the observed response-rate effect, not the trial’s design or an observed measure of power. They assume a two-sided significance level of 0.05, equal allocation, and a normal approximation. For planning for 100% of the observed effect, the illustration gives 4,520 participants per arm for 80% power and 6,050 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 8,085 participants per arm for 80% power and 10,822 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 18,300 participants per arm for 80% power and 24,497 participants per arm for 90% power.

These are hypothetical sample-size illustrations, not a statement about the planned or achieved power of this trial. They are particularly sensitive to the observed effect used as their starting point. The registry record does not report the trial’s sample-size justification or design assumptions, so the illustrations cannot be used to reconstruct those decisions.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies progression-free survival as the primary outcome and lists several secondary outcomes, but it does not report a statistical analysis plan describing how the family of outcomes was handled. In particular, multiplicity adjustment procedures, any hierarchy among secondary endpoints, and any division between confirmatory and exploratory analyses are not reported in the registry record. When multiple hypotheses are examined, unadjusted tests can make chance findings more likely across the set; this general issue limits the weight that can be placed on isolated secondary results.

The Full Analysis Set is defined as all participants randomized to study treatment. The primary endpoint arm counts are 75 and 78. The registry does not report how missing outcome assessments were handled, the censoring rules for PFS, whether any participants were excluded from a particular analysis, or the amount and pattern of missing data. It also does not report sensitivity analyses assessing the effect of missingness or deviations from the planned analysis.

The record lists zero reported analyses for the outcomes and does not provide a sponsor-reported formal comparison for PFS or objective response rate. The simple unadjusted response-rate calculation should therefore be distinguished from an analysis attributed to the sponsor. The registry also does not report interim analyses, stopping boundaries, the sample-size justification, or whether the termination affected the planned analyses. None of those design or analysis details can be inferred from the posted endpoint values.

These omissions do not mean that no such methods or analyses existed outside the registry; they mean the registry record does not document them. Without the analysis plan and fuller results, it is difficult to assess whether the posted estimates correspond to prespecified analyses, how uncertainty was controlled across outcomes, or how missing observations affected the conclusions.

11. 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: pneumonitis (7.8%), vomiting (6.8%), febrile neutropenia (5.4%), pneumonia (5.2%), nausea (4.1%).

The safety summary reports counts for participants with serious adverse events, participants with other adverse events, and deaths. In the M7824 sequence group, the serious adverse-event count was 43 of 74 at risk, the other adverse-event count was 68 of 74, and deaths numbered 13. In the placebo-then-durvalumab group, the corresponding counts were 31 of 77, 72 of 77, and 5. The at-risk counts differ from the primary endpoint arm counts, so the safety denominators should be used for these summaries.

These are descriptive counts. They do not establish that treatment caused an event or death, and the registry summary does not provide a comparative statistical analysis for these figures. The record lists serious adverse-event terms including pneumonitis (7.8%), vomiting (6.8%), febrile neutropenia (5.4%), pneumonia (5.2%), nausea (4.1%), and sepsis (4.1%). The listed terms are not broken down by treatment group in the registry record, so they should not be attributed to a particular arm.

Interpretation is limited because the registry does not provide event timing, duration, severity details beyond the serious-event designation, exposure-adjusted rates, or a full account of how adverse events were collected. Counts and percentages can depend on follow-up and exposure, and the posted summaries do not resolve those issues.

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

The results describe a randomized Phase 2 comparison of two treatment sequences in participants with unresectable Stage III non-small cell lung cancer. The primary endpoint was investigator-assessed PFS, and the posted median was 3.7 months in each group. The registry also reports response-rate estimates and adverse-event counts. These are observations from the study record, not a complete comparative analysis of every outcome.

The equal PFS medians do not demonstrate equivalence or prove that the treatment sequences have the same effect. Establishing equivalence or non-inferiority requires an appropriate design, prespecified margins, and comparative estimates with suitable uncertainty; those details are not reported in the registry record. Conversely, the posted summaries also do not establish that one sequence is superior. The registry lacks a sponsor-reported hazard ratio and formal primary comparison, which prevents a precise assessment of the relative PFS results.

The response-rate estimates are secondary and do not replace the primary endpoint. Their confidence intervals communicate uncertainty around each arm’s estimate, and the available unadjusted recalculation is exploratory. The safety summaries report counts, but they cannot determine causal attribution or provide a complete comparison of risks. The posted death counts are not accompanied by a cause-specific analysis in the record.

The study is listed as terminated. The registry record does not report why it was terminated, whether termination was related to efficacy or safety, or how it affected follow-up and data completeness. The values should therefore be interpreted as the results documented in the registry, without assuming an explanation for study status or extrapolating to patients beyond the trial population.

In short, these data document similar observed medians and provide descriptive secondary and safety information, but they do not supply the comparative statistical detail needed for a strong claim about relative treatment effects. They neither establish benefit nor establish lack of benefit for either treatment sequence.

13. Why This Trial Matters Statistically

This trial illustrates why a reported endpoint value and a comparative treatment estimate answer different questions. A median of 3.7 months in each group is an easily understood summary, but it does not show the full course of PFS or quantify how event rates compare over time. Reading the medians without a hazard ratio, confidence interval, or other formal comparison risks giving a single summary more meaning than it can support.

It also highlights the distinction between an arm-level range and uncertainty around a treatment effect. The registry labels the PFS dispersion as a full range. Such limits describe observed spread; they are not confidence intervals for the medians and do not replace a comparative interval. Correctly identifying what a reported interval represents is central to interpreting clinical trial results.

The record further demonstrates why secondary outcomes need context. Response rates can add useful descriptive information, but an unadjusted recalculation is not equivalent to a prespecified sponsor analysis, particularly when several outcomes are listed and no multiplicity plan is reported. Likewise, adverse-event counts are informative only with attention to their denominators and the limits of the available event detail.

Finally, planning illustrations based on an observed effect are not evidence of the study’s power or its original design. Without a reported sample-size justification, analysis plan, and complete comparative results, readers should separate what the registry documents from what might have been intended. The statistical lesson is not that the posted values are uninformative, but that their interpretation depends on estimands, uncertainty, analysis populations, and transparent reporting.

14. 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.

Several limitations specific to this record constrain interpretation. The study is listed as terminated, but the reason for termination is not reported in the registry record. The posted primary outcome provides arm medians and full-range limits, but no sponsor-reported hazard ratio, confidence interval for a between-group effect, event count, or formal primary comparison. The Kaplan-Meier method is named, but the survival curves and numbers at risk are not reported.

The primary endpoint was investigator-assessed under RECIST version 1.1. The registry record does not report independent central review, assessment schedules, adjudication procedures, or details of how missing or unevaluable assessments were handled. It also does not report the censoring rules or sensitivity analyses. These gaps limit assessment of measurement and follow-up effects.

The secondary results are incomplete for comparative interpretation. Objective response rates are posted, but no sponsor-reported analysis is listed. Numerical results for the other named secondary outcomes are not reported in the registry record. The multiplicity plan is also not reported, and the available unadjusted recalculation should not be treated as confirmatory.

Safety counts use denominators that differ from the primary endpoint counts, and the registry summary does not provide exposure-adjusted comparisons or arm-specific breakdowns for the listed serious adverse-event terms. The treatment duration, detailed chemotherapy selection process, and reason for termination are not reported. These omissions leave uncertainty about context, follow-up, and the completeness of the results, without indicating why those details are absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC) — NCT03840902.
• Registry record last updated 2024-01-16; status last verified 2024-01.
• Results first posted 2024-01-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This randomized, triple-masked Phase 2 study compared concurrent chemoradiation with M7824 followed by M7824 against concurrent chemoradiation with placebo followed by durvalumab in unresectable Stage III non-small cell lung cancer. The registry lists 153 participants enrolled and a terminated study status.

The primary outcome was investigator-assessed PFS by RECIST version 1.1. The posted median was 3.7 months in each group, with full-range limits of 1.9 to 5.6 months and 1.8 to 3.9 months, respectively. No sponsor-reported formal comparison for PFS is listed. Secondary results include objective response rates and adverse-event summaries; other named secondary outcomes do not have numerical results reported in the registry record.