QUILT-3.009: Patients With Stage III (IIIB) or Stage (IV) Merkel Cell Carcinoma (MCC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for QUILT-3.009: Patients With Stage III (IIIB) or Stage (IV) Merkel Cell Carcinoma (MCC) (NCT02465957), a non-randomized phase 2 study. The primary outcome is Number of Participants With Progression Free Survival Rate at 4 Months.

2. Clinical Question

3. Trial Design

This was a Phase 2 study sponsored by ImmunityBio, Inc. The registry describes its allocation as non-randomized, its masking as none, and its model as sequential. It lists aNK (NK-92) and aNK (NK-92) + N-803 as the intervention groups. These design features mean the record does not describe a blinded, randomized comparison. In particular, differences between the groups cannot be interpreted as if random assignment had balanced prognostic factors.

The listed enrollment was 7. The registry record does not report the number enrolled in each group for the primary outcome, or explain the sequence or rules by which participants entered the groups. Safety information lists 3 participants at risk in the aNK group and 4 in the combination group; these are the denominators for the posted safety figures, and should not be assumed to define the outcome analysis population.

The study started on 2015-09-24, had a primary completion date of 2018-03-19, and is listed as terminated. The record does not state why it was terminated. It describes the study as intended to determine the effects of aNK infusions in combination with ALT-803 in patients with the specified stages of MCC. A sample-size justification, planned enrollment rationale, and detailed protocol are not reported in the registry record.

The registry lists one outcome measure, the count of participants with progression-free survival at 4 months, and no analyses. It does not provide a reported efficacy result, a statistical analysis plan, or enough detail to establish how the primary endpoint was derived. The non-randomized design and small listed enrollment limit what can be learned from a comparison, even if outcome counts were available.

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 Number of Participants With Progression Free Survival Rate at 4 Months, measured over 4 months.

The primary endpoint is titled “Number of Participants With Progression Free Survival Rate at 4 Months.” Its unit is participants, and its parameter is a count of participants. The stated timeframe is 4 months. In general, progression-free survival describes time until disease progression or death, but the registry record does not provide the study-specific definition, assessment schedule, or rules for handling participants without an assessment at the time point.

A fixed-time outcome can give a concise description of how many participants meet an endpoint by a specified time. It may be easier to interpret than a time-to-event analysis when the question is explicitly about status at one time point. However, a count alone depends on how many participants were assessed and how missing or incomplete follow-up was handled. The record does not report those details or the primary outcome count, so the endpoint's value and precision cannot be evaluated from this record.

The title combines a count with the term “rate,” but the registry specifies participants and a count parameter rather than a reported rate. No denominator for the primary outcome, confidence interval, or estimate for either group is reported. Accordingly, the primary endpoint's statistical result cannot be reconstructed from the information in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as a count of participants. In general, a count records how many people meet a specified condition, while a proportion or rate requires a denominator and a defined observation period. Here, the endpoint title refers to a progression-free survival rate at 4 months, but its unit and parameter are listed as participants and a count. The record does not provide the number meeting the endpoint or a denominator for calculating a rate.

What does a fixed-time endpoint represent?

In general, a fixed-time endpoint evaluates participants' status at a specified point in follow-up. It differs from a time-to-event analysis, which uses the timing of events and can account for follow-up durations that differ across participants. The registry names 4 months as the endpoint timeframe, but does not report whether the primary analysis was limited to participants with an assessment at that time, used a time-to-event method, or handled incomplete follow-up in another way. No analysis method is reported.

The phrase progression-free survival commonly refers to remaining alive without documented progression, but operational definitions can differ. The timing and criteria for progression assessments, treatment of death, and rules for censoring or missing visits matter to the endpoint. None of those study-specific details are reported in the registry record. General definitions cannot replace the protocol's definition for interpreting a trial result.

Why does allocation matter?

The study is described as non-randomized, unmasked, and sequential. In general, random allocation is used to reduce systematic differences in participant characteristics between treatment groups. Without randomization, factors related to prognosis or treatment selection can differ across groups. Sequential enrollment may also coincide with changes in clinical practice or study conduct, although the record does not describe whether or how that occurred. The group results therefore would not support a straightforward causal comparison even if outcome counts were available.

Masking can reduce the influence of knowledge about treatment on outcome assessment or participant reporting. This study is listed as having no masking. Whether that could affect the primary outcome depends on the assessment procedures, which are not described in the registry record. It is not possible to determine from the record whether outcome assessment was independently reviewed.

What can uncertainty measures tell readers?

In general, a confidence interval expresses uncertainty around an estimate, under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while neither alone establishes whether a result is clinically important. For a count or proportion, the appropriate interval depends on the denominator and statistical method. No primary endpoint estimate, denominator, or confidence interval is reported, so precision cannot be assessed.

A p-value, when reported, measures how compatible data are with a specified null model under stated assumptions. It is not the probability that a treatment works, and it does not measure the size or importance of an effect. The registry lists no analyses and reports no p-value for the primary outcome. It is therefore not possible to assess statistical evidence for a group difference using this record.

How should planning illustrations be understood?

Sample-size calculations are planning tools: they describe the amount of information that might be needed to detect an assumed effect under specified conditions. They do not show what the study observed. The registry record does not report its own sample-size justification. Any planning illustration based on an observed effect is not evidence that the study had a particular probability of detecting an effect, and should not be described as observed power. The listed assumptions for such illustrations are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation; they describe the illustration rather than a reported trial analysis.

For outcomes with extra variability relative to a simple model, over-dispersion can make standard errors too small if it is ignored. In general, methods that account for over-dispersion can provide more realistic uncertainty. This endpoint is described as a binary count, and the registry does not report an over-dispersion assessment or a model for it. No additional modeling details should be inferred.

The record's one outcome measure and zero listed analyses leave important methodological questions unanswered. It does not state whether the primary analysis was intention-to-treat or used another analysis population, how missing outcome data were handled, or whether any adjustment for multiplicity was planned. These omissions prevent readers from evaluating the analysis strategy or reproducing a result from the registry record.

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("aNK (NK-92)", "aNK (NK-92) + N-803")
n      <- c(3, 4)
events <- c(3, 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  aNK (NK-92)  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  aNK (NK-92) + N-803  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 one outcome measure and no analyses. It does not report a statistical analysis plan or identify an analysis population for the primary endpoint. In particular, it is not reported whether the primary analysis would include all enrolled participants, only those who received treatment, or participants with an available outcome assessment.

Multiplicity arises when several outcomes, time points, treatment comparisons, or statistical tests are considered. In general, testing many hypotheses can increase the chance of at least one apparently unusual result, so a plan may specify how to control or interpret that issue. The record does not describe planned secondary outcomes, multiple testing procedures, or any adjustment for multiplicity. Because no analyses are listed, readers cannot determine what testing strategy was used.

The record also does not state how missing data were handled. For a fixed-time endpoint, participants may lack an assessment at the stated time point; how those cases are classified can affect the result. The registry does not give the number with missing assessments, the follow-up completeness, or any imputation or censoring method. These details are not reported in the registry record.

The listed enrollment is 7, but the endpoint's analysis denominator is not reported. Safety denominators should not be substituted for an efficacy denominator without confirmation that they refer to the same population and observation period. In the absence of analysis details and outcome data, no claim about the robustness of the endpoint result can be made.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: oedema peripheral (25.0%), sepsis (25.0%), encephalopathy (25.0%), hydronephrosis (25.0%), ureteric compression (25.0%).

The posted safety figures list 3 participants at risk in the aNK (NK-92) group and 4 in the aNK (NK-92) + N-803 group. Serious adverse events affected 0 of 3 in the aNK group and 2 of 4 in the combination group. Other adverse events affected 2 of 3 and 4 of 4, respectively. The record also lists 1 death in each group. These are descriptive counts in small groups, not estimates from a randomized comparison.

The record lists Oedema peripheral, Sepsis, Encephalopathy, Hydronephrosis, and Ureteric compression among the top serious adverse event terms, each at 25.0%. It does not make clear in the information whether those terms are associated with a particular group, whether participants could contribute more than one term, or how the percentages were calculated. The term list should not be used to infer distinct participant counts.

The registry record does not report whether deaths were considered related to treatment, nor does it provide detailed timing, duration, severity grading, or event-level attribution. A serious adverse event is not necessarily caused by an intervention. These data describe events recorded in the trial; they do not establish causation or provide a reliable comparative safety estimate.

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

The record establishes that a Phase 2 study of aNK, alone or with N-803, enrolled 7 participants and was terminated. Its stated primary outcome was the number of participants with progression-free survival at 4 months. The record does not include the primary outcome result, a statistical comparison, or a reason for termination. Consequently, it cannot show how many participants met the endpoint or how precisely the outcome was estimated.

The listed safety counts show serious adverse events affecting 0 of 3 participants in the aNK group and 2 of 4 in the combination group; deaths are listed for 1 participant in each group. Such small, non-randomized groups provide descriptive information only. They do not establish that an intervention caused an event, and they do not support a dependable comparison of risks.

In general, a trial's design, outcome definitions, analysis plan, and completeness of follow-up all shape the meaning of its results. Here, the lack of randomization limits causal interpretation, while missing primary outcome and analysis information prevents readers from assessing efficacy or precision. The registry's termination status is a study status, not an explanation of the result or of why the study ended.

These limitations do not prove that either intervention was ineffective or unsafe. They mean that the posted registry record does not provide enough information to answer the primary efficacy question or establish a comparative treatment effect. Any stronger conclusion would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it pairs a narrowly stated time-point outcome with a very small listed enrollment and a non-randomized design. Those features highlight the difference between having a defined research question and having enough reported results to answer it. The registry names progression-free survival at 4 months as the primary outcome, yet does not report the corresponding count or any analysis.

Non-randomized comparisons are vulnerable to baseline differences and other sources of confounding. A sequential model makes it especially important to understand how participants entered each group and whether enrollment or assessment procedures changed over time. Those details are not reported. The safety denominators are small, so each event count represents only a limited amount of information; the figures are best read descriptively rather than as stable estimates of comparative risk.

The record also illustrates why outcome definitions and analysis populations matter. A fixed-time endpoint depends on who was assessed, how progression was defined, and how incomplete follow-up was treated. Without those details, readers cannot determine the denominator, reconstruct the result, or assess its precision. A planned or calculated sample-size illustration cannot replace observed outcome data, and the record does not report the study's own sample-size justification.

More broadly, registry entries can communicate important design and status information while leaving the main result unavailable. Separating what is documented—study design, enrollment, endpoint name, and safety counts—from what remains unknown is essential for sound statistical interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation is that the registry record does not report the primary endpoint result. It provides no count or rate for progression-free survival at 4 months, no outcome denominator, and no confidence interval or p-value. As a result, neither the endpoint's direction nor its precision can be assessed from this record.

The listed enrollment is 7, and safety information gives small at-risk groups of 3 and 4 participants. These figures do not provide a basis for a robust efficacy comparison. In addition, the study is non-randomized, unmasked, and sequential. The record does not describe group assignment procedures, baseline characteristics, or the timing of each group's enrollment, so potential selection effects and time-related differences cannot be evaluated.

Important endpoint details are absent. The registry does not state the operational definition of progression-free survival, how progression was assessed, the primary analysis population, the number assessed at 4 months, or how missing data were handled. It also lists no analyses and does not report a statistical analysis plan, multiplicity procedures, or the study's sample-size justification.

The record lists the study as terminated but does not report the reason. It provides selected adverse-event counts and terms without enough detail to determine event-level attribution, timing, or treatment relationship. These limitations are specific to the information available in the registry record; they do not establish what may have been collected or analyzed outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: QUILT-3.009: Patients With Stage III (IIIB) or Stage (IV) Merkel Cell Carcinoma (MCC) — NCT02465957.
• Registry record last updated 2024-05-02; status last verified 2020-08.
• Results first posted 2024-05-02.
• 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

This registry record describes a Phase 2, non-randomized, unmasked, sequential study of aNK (NK-92), alone or with N-803, for Stage III (IIIB) or Stage IV Merkel Cell Carcinoma. The listed enrollment is 7. The study started on 2015-09-24, reached primary completion on 2018-03-19, and is listed as terminated.

The primary outcome was the number of participants with progression-free survival at 4 months. The registry lists one outcome measure and no analyses, and does not report the primary outcome result, its analysis population, or the reason for termination. Safety counts are reported for 3 participants in the aNK group and 4 in the combination group. These descriptive figures do not support a randomized comparison or establish causation.