QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy (NCT03853317), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

3. Trial Design

This is a phase 2, single-group study of avelumab, haNK and N-803 in people with Merkel cell carcinoma that progressed on or after checkpoint inhibitor therapy. The record lists nine participants as enrolled. It lists no separate comparison arm, and allocation is marked NA. The masking entry is NONE, so no masking is listed. Without a concurrent comparator group, the study can describe outcomes among participants receiving the combination, but it cannot estimate a randomized between-group treatment effect.

The brief summary says the combination was being evaluated by objective response rate and that participants could receive treatment for a maximum of two years. The arm description specifies objective response rate under RECIST 1.1 as the efficacy objective. The registry’s primary outcome entry, however, is the number of participants with adverse events. Its stated timeframe is 30 days after the last dose, approximately 1 year 7 months. The record does not explain the difference between the efficacy objective and the primary outcome entry.

The study is marked terminated. The record gives a start date of 2020-02-19 and a primary completion date of 2021-09-29. A reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or whether it ended as planned. The sponsor is ImmunityBio, Inc. The registry record does not describe a sample-size justification, an interim analysis plan, or the statistical plan used for efficacy outcomes. Those omissions limit what can be inferred about how the study was intended to answer its efficacy question.

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:

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 Adverse Events, measured over 30 days after last dose, approximately 1 year 7 months.

The registry’s primary outcome is the number of participants with adverse events. This is a count of participants who experienced an event, rather than a measure of event severity, duration, or time until an event. The specified observation timeframe is 30 days after the last dose, approximately 1 year 7 months. The outcome description frames the count as a safety assessment of the combination in people with Merkel cell carcinoma that progressed on or after checkpoint inhibitor therapy.

In general, adverse-event monitoring is used to describe unwanted medical events observed during a study and within a stated follow-up period. A participant count is useful for communicating how many people were affected, but it does not by itself describe how many events each person had, when events occurred, or whether investigators judged them related to treatment. Those details are not reported in the registry record for this outcome.

The registry also describes objective response rate by RECIST 1.1 as the primary efficacy objective. Response rate concerns whether participants meet criteria for a specified tumor response; it is distinct from an adverse-event count. The record lists response-related secondary outcomes, but it reports no analyses. Therefore, the available primary outcome information supports a description of safety counts, not an estimate of response or efficacy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the study treatment. It can report counts or outcome values observed in that group, but it does not directly estimate what would have happened to comparable participants under a different treatment. A comparator group, and a design that supports a fair comparison, are needed to estimate a between-treatment contrast. This record lists a single group and no comparator, so the posted counts should be read descriptively.

The allocation entry is NA, consistent with the registry’s single-group model. Masking is listed as NONE. These design entries describe the structure recorded in the registry; they do not provide details about how participants were selected or evaluated. Further information about those procedures is not reported in the registry record.

What does a participant count mean?

The primary outcome is defined as the number of participants with adverse events. A participant count records whether people experienced an event during the stated observation period. It is not an event count: a person who experienced multiple events may still contribute once to a count of participants affected, depending on the outcome definition. The record does not give a more detailed counting rule, such as how repeat events were handled or how the event window was applied to each participant.

In general, counts are easiest to interpret alongside the number of people at risk and a clear follow-up period. Here, the registry reports the at-risk and affected counts for serious and other adverse events, and gives the primary outcome timeframe as 30 days after the last dose, approximately 1 year 7 months. The record does not report person-time or event timing, so these counts should not be read as rates over time.

Why distinguish serious from other adverse events?

Seriousness is a classification of an adverse event, not a synonym for frequency or for a causal relationship to treatment. In general, serious and non-serious event summaries answer different descriptive questions. They should not be combined unless the definitions and analysis explicitly support that operation. The registry presents separate counts for serious adverse events and other adverse events; it does not explain whether these categories are mutually exclusive at the participant level. A participant could have events in more than one category, so the counts should not be added to infer a number of people affected overall.

Term-level percentages describe the reported serious-event terms. They do not reveal the total number of events, whether terms occurred in the same person, or how investigators assessed causality. Those details are not reported in the registry record. The terms therefore provide a limited description rather than a complete safety profile.

What can an uncertainty interval tell a reader?

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the statistical method. It is not a guarantee that the true value lies within the interval, and it does not correct for limitations such as lack of a comparator or incomplete outcome reporting. No confidence intervals are reported for the adverse-event counts in this record. The reader therefore cannot use posted interval estimates to assess the precision of those counts.

For a response outcome, the record says that objective response rate was to be assessed using RECIST 1.1. It does not report the response count or an estimated response rate, and no analysis is listed. Without an estimate and its uncertainty, the response objective cannot be interpreted quantitatively from the posted results. The same limitation applies to the listed time-to-event and other secondary outcomes.

What do the planning assumptions represent?

In general, sample-size planning asks how much information a future study might need under stated assumptions. A planning illustration is not an observed treatment effect, an outcome from this study, or observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events, while other illustrations express participants per arm.

Those assumptions describe the calculation framework, not the design recorded for this single-group trial. The record does not report the trial’s own sample-size justification or design assumptions. Since there is no comparator arm in the registry design, an illustration based on equal allocation between two arms should not be mistaken for the study’s observed design or for a comparison made in its posted results.

The record lists no analyses. It does not provide a statistical model for the safety count, an adjustment strategy, confidence intervals, or hypothesis tests for the efficacy outcomes. Without those details and the corresponding estimates, statistical precision and inferential conclusions cannot be evaluated 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("Treatment With Avelumab, haNK™ and N-803")
n      <- c(9)
events <- c(9)
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  Treatment With Avelumab, haNK™ and N-803  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including response by iRECIST, progression-free survival, overall survival, disease-specific survival, disease control rate, and FACT-M Total Score. Some outcome labels appear more than once in the list, but the registry record does not explain whether those entries refer to distinct analyses, timepoints, or definitions. It also does not report a multiplicity strategy for interpreting results across outcomes. In general, when many outcomes are examined, a prespecified approach to multiplicity can help clarify how false-positive findings are controlled; the approach used is not reported in the registry record.

The analysis population is not described for the primary outcome, and the record does not state how missing observations were handled. It does not report whether participants who stopped treatment, missed assessments, or lacked follow-up were included in each outcome analysis. Such information matters because the set of people contributing to an estimate can affect its interpretation. The record gives adverse-event at-risk counts, but that alone does not specify the analysis population or missing-data rules for other outcomes.

The registry lists no analyses. Consequently, there are no posted outcome estimates on which to assess multiplicity adjustments, missing-data handling, or analysis-population definitions. The record also does not report an interim analysis plan or a statistical analysis plan. These omissions do not show what procedures may have been used outside the registry; they mean the relevant methods cannot be verified from the registry record.

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: anaemia (22.2%), oedema peripheral (11.1%), infusion related reaction (11.1%), haematuria (11.1%).

The registry reports nine participants at risk for serious adverse events, with five affected. For other adverse events, it reports nine at risk and nine affected. It also reports four deaths. These are counts in the treatment group, not comparative estimates. The record does not state whether the deaths were treatment-related, what caused them, or when they occurred. It also does not provide enough information to attribute the adverse events to the study treatment.

The listed serious-event terms are Anaemia at 22.2%, Oedema peripheral at 11.1%, Infusion related reaction at 11.1%, and Haematuria at 11.1%. These percentages should be read as reported term-level summaries. The registry does not specify whether listed terms occurred in the same participants, whether each participant could contribute multiple terms, or how the percentages were calculated beyond the posted values. They are not a complete account of all adverse events.

In general, serious-event and other-event categories should be interpreted according to their definitions and not added together unless the reporting method establishes that they are non-overlapping. The registry record does not clarify participant-level overlap. It also does not report event severity grades, duration, treatment attribution, or details of event management. The figures therefore describe reported safety counts, but do not establish comparative risk or causality.

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

The posted information establishes that this was a phase 2, single-group study of avelumab, haNK and N-803 in Merkel cell carcinoma that progressed on or after checkpoint inhibitor therapy. The registry reports nine enrolled participants and gives adverse-event counts, serious-event terms, and deaths. Those data allow a limited description of what was recorded for the treated group.

The record does not report analyses of the efficacy outcomes. Although the study description identifies objective response rate under RECIST 1.1 as an efficacy objective, no response estimate is reported. The same is true for the listed secondary outcomes. As a result, the posted record does not quantify tumor response, disease control, or survival outcomes. A stated objective is not itself evidence of an observed result.

The absence of a comparator means that the adverse-event counts cannot show whether the combination changed risk relative to another treatment or to no study treatment. The counts also cannot establish that treatment caused the events or deaths. In general, causal interpretation requires evidence that addresses alternative explanations; a single-group descriptive count does not provide that comparison. The registry does not report event attribution or enough clinical detail to resolve causality.

The results should also be understood in light of the limited information reported. No confidence intervals, analysis populations, missing-data methods, or statistical plan are listed. The record is marked terminated, but it does not report the reason. These registry entries constrain interpretation; they do not establish that particular analyses were impossible or that particular outcomes were absent from all study records.

Accordingly, the record supports a cautious reading of the reported safety summaries and the study’s design. It does not support a treatment recommendation, a conclusion of benefit or lack of benefit, or a comparative safety claim. Such conclusions would require evidence beyond the outcomes and analyses reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a study objective and a posted outcome result. The description identifies objective response rate as the efficacy objective, while the primary outcome entry is a participant count for adverse events. That distinction matters: safety counts and tumor-response estimates address different questions and require different outcome definitions and analyses.

The single-group design also sets a clear boundary on inference. It can document outcomes among participants receiving the combination, but it has no concurrent comparator for estimating a treatment contrast. This is important when reading adverse-event summaries, because observed events cannot be separated from the effects of disease history, prior checkpoint inhibitor therapy, or other influences using the registry counts alone.

The registry reports safety counts and selected serious-event terms, but no analyses for the efficacy outcomes. This makes transparent reporting of outcome estimates and uncertainty especially important: readers need results, analysis populations, and methods to judge what the data can support. The registry record does not report those details for efficacy analyses, nor does it report the missing-data or multiplicity approaches.

Finally, the terminated status is part of the study record but does not explain why the study ended. Without a reported reason or analysis plan, the status should not be used to infer the cause of termination or the status of unreported efficacy analyses. The statistical lesson is one of scope: design, outcome definitions, and accessible analysis results together determine which conclusions are justified. Here, the record permits a narrow descriptive account of reported safety information, while leaving efficacy and comparative questions unanswered.

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 registry record has several limitations specific to interpretation of this study. It lists nine participants enrolled, with no comparator group. A single-group study cannot provide a randomized estimate of how outcomes compare with another treatment. The small enrolled group also limits how precisely its observed counts can describe outcomes in a broader population; no uncertainty intervals are reported for the safety counts.

The record is marked terminated, but does not give a reason for termination. It provides a primary completion date of 2021-09-29, yet does not explain whether the termination altered outcome collection or planned analyses. The registry’s primary outcome is a count of participants with adverse events, while the study description states an efficacy objective based on objective response rate under RECIST 1.1. The record does not explain the relationship between these descriptions.

Although secondary outcomes are listed, the registry reports no analyses. It therefore does not provide efficacy estimates or their precision. Detailed eligibility criteria, baseline participant characteristics, treatment exposure, follow-up completeness, analysis populations, and missing-data handling are not reported in the registry record. The available safety counts do not supply these details.

The record also does not give event-level descriptions sufficient to assess timing, duration, severity, attribution, or overlap among reported terms. The reasons for deaths are not reported. No statistical analysis plan, multiplicity strategy, interim analysis plan, or sample-size justification is reported in the registry record. These limitations do not establish what information may exist elsewhere; they define what can be concluded from this registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy — NCT03853317.
• Registry record last updated 2024-08-09; status last verified 2024-08.
• Results first posted 2024-08-09.
• 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

NCT03853317 is a phase 2, single-group study sponsored by ImmunityBio, Inc. It evaluated avelumab, haNK and N-803 in people with Merkel cell carcinoma that progressed on or after checkpoint inhibitor therapy. The record lists nine participants enrolled, a start date of 2020-02-19, a primary completion date of 2021-09-29, and status as terminated. The brief summary says treatment could continue for a maximum of two years.

The registry’s primary outcome is the number of participants with adverse events, with a timeframe of 30 days after the last dose, approximately 1 year 7 months. The record reports counts for serious and other adverse events, four deaths, and selected serious-event terms. The study description names objective response rate by RECIST 1.1 as the efficacy objective, but the registry lists no analyses. A comparator, reason for termination, and detailed statistical and missing-data methods are not reported in the registry record.