Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma (NCT02408016), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

3. Trial Design

This was a phase I/II, non-randomized, unmasked, parallel-arm study sponsored by Fred Hutchinson Cancer Center. The registry title describes genetically modified T cells for patients with stage III-IV non-small cell lung cancer or mesothelioma. The official title specifies WT1-expressing disease and compares adoptive cellular immunotherapy using central-memory to naïve CD8-positive T cells transduced to express a WT1-specific T-cell receptor.

The registry records enrollment of 11 and lists a start date of 2015-05-22 and a primary completion date of 2020-06-30. Its current status is terminated. The reason for termination is not reported in the registry record. Nor does the record explain whether the enrollment figure represents all enrolled patients, all treated patients, or the population contributing to each posted outcome.

Arm I had Stage I and Stage II treatment schedules. Both involved the autologous WT1-TCRc4 gene-transduced T cells, cyclophosphamide, and aldesleukin, but the timing and sequence differed. Arm II involved the modified T cells and aldesleukin, followed by surgery. The primary-outcome population description specifically states that no patients were treated in Arm II. The posted adverse-event data give at-risk counts for the two Arm I stages, while Arm II has zero participants at risk.

Non-random allocation means the arms were not formed by random assignment. The registry also states that arms are not a like-for-like control comparison. The design therefore supports a descriptive account of the listed safety counts, but not a causal comparison of treatment strategies. No protocol rationale for the arm structure, allocation process, or termination is reported in the registry record.

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: 11 participants were enrolled, but only 10 participants were assigned to an arm/group.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: No patients were treated in Arm II.

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: No patients were treated in Arm II

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over Up to 6 months after the first T cell infusion.

The primary endpoint is the number of participants with adverse events, with a timeframe of up to 6 months after the first T cell infusion. The registry says adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. This is a participant-count outcome: it records whether participants experienced events within the defined assessment period, rather than presenting an event rate per unit of follow-up or a time-to-first-event estimate.

Safety outcomes are commonly used in early-phase clinical research to describe unwanted effects observed during treatment and follow-up. In general, severity grading helps distinguish serious events from other events, while participant counts communicate how many people were affected in each group. These measures can inform how tolerable a regimen appeared among those assessed, but their interpretation depends on complete follow-up, consistent event definitions, and clear attribution procedures.

The posted record gives counts for participants with serious adverse events, other adverse events, and deaths. It does not provide event-level descriptions for the serious events, and the list of top serious terms is empty. The endpoint title and timeframe do not establish that every listed death was an adverse event or treatment-related. The registry record does not report causality assessments or explain how missing safety follow-up was handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary participant-count outcome: whether participants were recorded as having an event. In general, a binary outcome reduces each participant’s experience to an event or no-event classification for the measure being reported. For safety summaries, separate event categories may be presented, as in the registry’s serious adverse-event, other-adverse-event, and death counts. These categories are not interchangeable. A participant may experience multiple events, but a participant-count measure does not show the number of event episodes unless the registry reports those separately.

What does a count describe?

A count describes the number of participants with the specified outcome in the group at risk. Interpreting it alongside the at-risk count gives context about the group contributing to that outcome. In the posted data, the serious adverse-event counts are 0 among 6 at risk in Arm I, Stage I and 0 among 4 at risk in Arm I, Stage II. The other adverse-event counts are 6 among 6 at risk and 3 among 4 at risk, respectively. Arm II has no participants at risk. These are observations in the registry record, not estimates adjusted for differences among participants or treatment exposure.

In general, a proportion can be used to express an event count relative to the number at risk, but no additional proportions are needed to describe these posted counts. Even when a proportion is reported, uncertainty matters: a confidence interval describes a range of values compatible with the data under its statistical assumptions. The registry record does not report confidence intervals for these safety counts. With small groups, estimates can be imprecise, and a zero observed count does not prove that the underlying event risk is zero.

Why does study allocation matter?

Random allocation is a method intended to balance, on average, factors that may affect outcomes between treatment groups. This study is listed as non-randomized. In general, non-randomized groups can differ in disease characteristics, eligibility, treatment timing, or other prognostic factors. Those differences can influence safety outcomes independently of the treatment being compared. Here, the record also says that the arms are not a like-for-like control comparison, and there were no treated participants in Arm II. Thus, between-arm contrasts cannot be interpreted as randomized causal effects.

The parallel model means the registry organized treatment groups as arms rather than describing a crossover sequence. The record is unmasked, so treatment assignment was not masked. For adverse-event reporting, lack of masking can matter in general because expectations and knowledge of treatment may influence symptom reporting, clinical observation, or event classification. The registry does not describe any measures used to reduce such influence.

How should the safety timeframe be read?

The primary outcome covers up to 6 months after the first T cell infusion. A fixed follow-up window helps define which events are counted for the endpoint. In general, however, participants may have different amounts of observed follow-up if they enter at different times or leave observation early. The record does not report individual follow-up duration, completeness of safety assessments, or rules for handling participants with incomplete observation. The timeframe should therefore be understood as the stated assessment period, not proof that every participant was observed throughout it.

The registry cites Common Terminology Criteria for Adverse Events version 4.0. In general, standardized criteria support consistent classification and severity grading. The posted summary does not supply grades, event narratives, attribution judgments, or the methods used to collect events. The empty list of top serious terms means no serious-event terms are listed in that field; it should not be read as a detailed clinical account.

What can planning calculations tell a reader?

Sample-size calculations are planning illustrations, not observed outcomes. In general, a calculation based on an observed effect asks how many participants might be needed under stated assumptions to detect an effect of a chosen size. The registry’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. Such calculations are not the study’s original design justification unless the record says they were, and the registry does not report that justification.

For participant-count outcomes, planning calculations expressed per arm describe a hypothetical future study under their assumptions. They do not indicate that the current study had a particular probability of detecting an effect. In general, observed power is not a substitute for reporting an estimate and its uncertainty. The registry record reports no analyses, and it gives no inferential estimates for the safety outcome. A planning illustration cannot fill that gap, establish an effect, or repair the lack of a treated comparator.

No statistical analysis plan, adjustment strategy, interim analysis plan, or sample-size rationale is reported in the registry record. Without those details, it is not possible to determine whether any planned analyses were changed, how multiple outcomes were treated, or what rules governed the analysis population. The available interpretation should therefore remain close to the posted counts and the stated design.

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("Arm I, Stage I (T Lymphocytes, Cyclophosphamide, I", "Arm I, Stage II (T Lymphocytes, Cyclophosphamide, ")
n      <- c(6, 4)
events <- c(6, 3)
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  Arm I, Stage I (T Lymphocytes, Cyclophosphamide, I  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Arm I, Stage II (T Lymphocytes, Cyclophosphamide,   4  3  75.0  19.4  99.4  30.1  95.4  28.4  94.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures and reports 0 analyses. It does not describe an analysis plan for controlling multiplicity, choosing among outcomes, or interpreting repeated statistical tests. In general, when a study evaluates multiple outcomes, testing many hypotheses can increase the chance of at least one apparently notable result by chance. Methods such as prespecifying a primary outcome or adjusting inference can address particular multiplicity concerns, but the registry record does not report which, if any, were used. No multiplicity-adjusted results are posted.

Missing-data handling is also not reported in the registry record. The endpoint has a timeframe of up to 6 months after the first T cell infusion, but the record does not say whether all participants completed that period, how early withdrawal or incomplete event reporting was handled, or whether the at-risk counts reflect complete follow-up. For a safety endpoint, incomplete observation can affect whether an event is recorded; the posted counts alone do not establish complete ascertainment.

The primary-outcome population description states that no patients were treated in Arm II. The record does not give a fuller analysis-population definition or explain how enrolled participants were included in each outcome. It reports enrollment of 11, while the listed at-risk counts are 6 for Arm I, Stage I, 4 for Arm I, Stage II, and 0 for Arm II. The reason for the relationship between these figures is not reported in the registry record. There is no reported intention-to-treat definition, per-protocol rule, or account of exclusions. These omissions limit assessment of whether the posted counts represent all enrolled patients, all treated patients, or another defined population.

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 non-serious adverse event terms

The registry lists serious adverse events for Arm I, Stage I as 0 participants affected among 6 at risk, and for Arm I, Stage II as 0 among 4 at risk. Other adverse events are listed for 6 among 6 at risk in Stage I and 3 among 4 at risk in Stage II. Arm II has 0 participants at risk and no listed events; the primary-outcome population description says no patients were treated in that arm.

Deaths are listed as 6 in Arm I, Stage I and 2 in Arm I, Stage II. The registry does not give causes, timing, or a judgment about whether the deaths were related to treatment. These death counts should therefore be read as reported outcome data, not as treatment-attributed deaths. The record does not give event-level details for serious adverse events, and the top serious terms list is empty.

In general, an adverse-event count describes occurrence, not causation. It also does not convey the number of event episodes, seriousness of other events, duration, or recovery unless those details are separately reported. The posted counts do not establish that every participant had complete follow-up through the stated timeframe.

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

The registry record documents a terminated phase I/II study of WT1-specific, gene-transduced autologous T cells in people with non-small cell lung cancer or mesothelioma. Its primary outcome is a count of participants with adverse events up to 6 months after the first T cell infusion, assessed using Common Terminology Criteria for Adverse Events version 4.0. The available results are counts from the two Arm I stages; no patients were treated in Arm II according to the primary-outcome population description.

The results describe what was recorded in those groups: no serious adverse events were listed among the participants at risk in either Arm I stage; other adverse events were recorded in both stages; and deaths were listed in both stages. The record does not report the details needed to determine whether deaths or other events were caused by treatment. It also does not provide confidence intervals or an inferential analysis, so the precision of comparisons cannot be quantified from the posted results.

These observations do not show whether the treatment improves cancer outcomes. No efficacy result is included in the registry record for this analysis. Nor do the counts establish that one Arm I schedule is safer than the other: the study was non-randomized, the schedules differed, and the groups are not identified as comparable. Arm II cannot serve as a treated control because no patients were treated in that arm.

In general, safety findings from early-phase research can describe events observed during a particular study, but they do not by themselves establish the frequency of events in a broader population. Group size, follow-up completeness, event definitions, and attribution all affect interpretation. Here, the registry does not report the reason for termination, a complete account of follow-up, or analysis-population rules. The result is therefore a limited descriptive record, not a definitive estimate of treatment risk or benefit.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its registry contains safety counts in a setting where the study design sharply limits comparison. A non-randomized allocation does not ensure that groups share similar prognostic characteristics, and the registry explicitly cautions that the arms are not a like-for-like control comparison. The absence of treated participants in Arm II makes that limitation especially clear: an arm listed in a design description does not automatically provide outcome data for a treatment comparison.

The record also illustrates why counts should be read with their denominators and population definitions. The same event count has a different context depending on how many participants were at risk and how outcome observation was defined. Even with those counts, the registry does not report confidence intervals, event-level descriptions, follow-up completeness, or analysis-population rules. Statistical interpretation depends not only on a number, but on how the contributing observations were collected and selected.

Another important distinction is between a planning calculation and evidence from the study. A sample-size illustration based on an observed effect uses assumptions to describe a hypothetical future design. It is not a randomized comparison, not an analysis of treatment efficacy, and not a measure of observed power. The record does not report the study’s original sample-size justification, so planning assumptions should not be mistaken for the trial’s rationale.

Finally, the outcome terminology matters. Participant counts with adverse events, serious adverse events, and deaths convey different information, and none alone identifies causation. Reading the record carefully avoids treating a zero serious-event count as proof of no risk or treating deaths listed in an outcome field as treatment-related. The limitations are part of the statistical result, not a reason to infer more than the record supports.

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.

Several trial-specific limitations restrict interpretation. The study was non-randomized and unmasked, and the registry cautions that the arms are not a like-for-like control comparison. The treatment schedules also differed across the Arm I stages. Consequently, the listed group counts cannot isolate a causal effect of one regimen or schedule relative to another.

The primary-outcome population description states that no patients were treated in Arm II. The at-risk count for that arm is zero, so it provides no treated outcome data for comparison. The registry reports enrollment of 11, while the posted at-risk counts are 6 for Arm I, Stage I, 4 for Arm I, Stage II, and 0 for Arm II; the relationship between enrollment and these outcome populations is not reported in the registry record.

The study is listed as terminated, but the reason is not reported in the registry record. The record does not report whether safety follow-up was complete, how missing observations were handled, or whether deaths occurred during the stated endpoint timeframe. It also does not provide event-level descriptions, grades for other adverse events, or causal assessments. The empty serious-event terms field does not supply those missing details.

There are no posted statistical analyses or uncertainty estimates for the outcome. The registry record does not report an analysis plan, sample-size justification, interim analysis procedures, or rules for selecting the analysis population. These omissions leave the descriptive counts as the main available basis for interpretation and prevent assessment of planned versus reported analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma — NCT02408016.
• Registry record last updated 2021-09-13; status last verified 2021-08.
• Results first posted 2021-09-13.
• 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

The registry record identifies NCT02408016 as a phase I/II, non-randomized, unmasked, parallel study sponsored by Fred Hutchinson Cancer Center. It concerns WT1-directed, genetically modified autologous T cells for stage III-IV non-small cell lung cancer or mesothelioma. The record lists enrollment of 11, a start date of 2015-05-22, a primary completion date of 2020-06-30, and terminated status.

The primary outcome counts participants with adverse events up to 6 months after the first T cell infusion, using Common Terminology Criteria for Adverse Events version 4.0. The posted outcome data include serious adverse events, other adverse events, and deaths for the two Arm I stages. The primary-outcome population description says no patients were treated in Arm II. No statistical analyses are reported in the registry record. The reason for termination, missing-data procedures, analysis-population rules, and causal attribution of deaths or other events are not reported in the registry record.