QUILT-3.040: ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) Vaccine in Combination With ALT-803 (Super-agonist IL-15) in Subjects Having CEA-Expressing Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for QUILT-3.040: ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) Vaccine in Combination With ALT-803 (Super-agonist IL-15) in Subjects Having CEA-Expressing Cancer (NCT03127098), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Dose-Limiting Toxicities.

2. Clinical Question

The study’s stated aims were to evaluate safety, tolerability, and efficacy of the combination. The primary outcome focuses on dose-limiting toxicities, a measure used in early-phase dose-escalation studies to characterize treatment-limiting safety findings. It is a count of participants, rather than a comparison of the combination with another treatment. The registry record does not report a primary-outcome result, the toxicity criteria used, or a dose level associated with any outcome.

Duration of Response, Progression Free Survival, and Overall Survival are listed as secondary outcomes. Their results are not reported in the registry record. With no randomized comparator identified and only 3 participants enrolled, this record does not establish a comparative effect of the combination. It documents a small sequential study and the outcomes it set out to assess, rather than a completed efficacy comparison.

3. Trial Design

This was a phase 1b/2 study of ETBX-011 in combination with ALT-803. The registry describes a sequential dose-escalation study in subjects with CEA-expressing cancers. The intervention group is named ETBX-011 in Combination With ALT-803, and its description says a combination of agents was administered in a dose-escalation study. The registry record does not report the sequence of dose levels, dose amounts, or rules for moving between levels.

Allocation is recorded as NA, masking as none, and the model as sequential. No concurrent control arm is identified, so the design is not a randomized comparison. The listed cancers are thyroid, colon, ovarian, breast, lung, and pancreatic cancer. The brief summary further describes locally advanced or metastatic CEA-expressing cancers that had recurred after standard-of-care treatment.

Enrollment was 3. The study started on 2017-06-26, and primary completion was recorded as 2017-12-07. Its status is terminated. The reason for termination, whether enrollment was completed as planned, and any protocol changes are not reported in the registry record. Nor does the registry record explain whether the phase 1b/2 study had separate stages or how participants moved through them. Those details should not be inferred from the phase label or the sequential model alone.

Three secondary outcomes are named: Duration of Response, Progression Free Survival, and Overall Survival. The primary outcome is the number of participants with dose-limiting toxicities over 9 weeks. Although the registry indicates four outcome measures, only these three secondary outcomes and the primary outcome are described in the listed information. The number of analyses is recorded as 0, and no outcome analysis is 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.

Before assignment: Only the first dose level, N-803 10 μg/kg/dose + ETBX-011 (5 × 10\^11 VP/dose), was administered due to study termination. No additional escalations or the expansion phase (Phase 2) occurred. No patients had a response, therefore, Duration of Response could not be summarized. Only 2 out of 3 enrolled patients had a response assessment data, therefore, Progression Free Survival and Overall Survival analyses will not provide a meaningful result.

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 Dose-Limiting Toxicities, measured over 9 weeks.

The primary outcome is the number of participants with dose-limiting toxicities during a 9-week timeframe. It is recorded as a participant count. The registry record does not provide a result for this outcome, a definition of dose-limiting toxicity, or the dose levels to which participants were exposed.

In general, dose-limiting toxicity is used in early-phase dose-escalation research to identify treatment-related safety findings considered important enough to constrain further dosing. A count can describe how many participants met the study’s prespecified criteria, but interpreting that count requires knowing the criteria, observation period, dose received, and number of participants assessed. These details affect what the count means and how it can be compared across studies.

The endpoint’s stated timeframe is 9 weeks. The record does not explain how participants with incomplete follow-up would be handled, whether toxicity attribution was required, or how events arising after that period would be considered. No estimate of uncertainty, such as a confidence interval, is reported. The registry therefore identifies the primary safety question, but does not provide enough outcome information to assess the observed frequency or precision of dose-limiting toxicity.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is sparse. It describes the study as sequential and records allocation as NA and masking as none. It does not report a statistical analysis plan, specific tests, estimation procedures, confidence intervals, interim analyses, or rules for handling missing observations. The number of analyses is recorded as 0. Accordingly, statistical concepts can help explain what the listed measures would mean in general, but no unreported method should be attributed to this study.

What does a participant count measure?

The primary outcome is a count of participants with dose-limiting toxicities, with a 9-week timeframe. A count is a direct tally, not a comparison between treatment groups and not a time-to-event estimate. To interpret it, readers would need the number assessed, the number meeting the toxicity definition, and the criteria used to classify a toxicity as dose-limiting. The registry record does not report the outcome count or these criteria.

Counts are often presented alongside the number of people who could have experienced the outcome. That denominator matters because identical counts can have different meanings in groups of different sizes. Here, the record gives enrollment of 3 and adverse-event at-risk counts of 3, but does not give an assessed denominator for the primary outcome or confirm how missing follow-up was handled. The adverse-event denominators should not automatically be assumed to be the denominator for the primary endpoint.

What would uncertainty describe?

In general, a confidence interval expresses the range of values reasonably compatible with an estimate under a specified statistical method. It reflects sampling uncertainty, not all sources of uncertainty: it cannot account for unmeasured differences, incomplete reporting, or limitations in study design. For a small participant count, an estimate can be imprecise, and the interval may be wide. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be evaluated.

A p-value, when used, describes how compatible data are with a specified null model under stated assumptions. It does not measure the probability that a treatment works, nor does it establish clinical importance. The registry record reports no p-value or statistical test for the primary outcome. There is also no reported analysis plan that would establish which tests, if any, were intended.

How does the design affect inference?

A randomized, concurrent comparison can help distinguish treatment-related differences from changes that might occur over time or from differences between participant groups. This study has no listed control arm and is not identified as randomized. Its sequential dose-escalation design is oriented toward administering combinations at successive dose levels, but the record does not give the rules or dose details. Results from a single treated group therefore cannot establish a relative effect against another treatment.

In general, a sequential design can make observations at one stage relevant to decisions at a later stage. That does not mean any particular decision rule or adaptive statistical method was used in this study. The registry record does not report an escalation algorithm, stopping boundaries, interim analyses, or a dose-selection method. Those features must remain unknown rather than being inferred from the design label.

What do the planning assumptions mean?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses the total number of events under the Schoenfeld approach; for other outcomes, it expresses sample size as participants per arm. These are hypothetical planning assumptions, not a description of the enrolled study’s design. In particular, the study record identifies no two-arm randomized comparison.

The numerical planning estimates and the observed effect used to generate them are not reported in the registry record. Such planning quantities are not observed power and do not describe the precision of this trial’s results. Sample-size planning asks what enrollment might be needed under chosen assumptions; it does not change the information actually collected or supply missing outcome estimates.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume that variability follows a particular relationship to the average count. Over-dispersion means observed variability is greater than that model expects. If it is ignored, standard errors can be too small and uncertainty can appear overstated in precision. This is a general consideration, not a reported feature of this study: the registry record does not describe a count model, dispersion estimate, or model-based analysis. The primary endpoint is a participant count, and no analysis is reported that would allow assessment of distributional assumptions.

More broadly, no model, adjustment strategy, analysis population, or missing-data procedure is reported. The registry record supports only a limited descriptive reading of the enrollment and adverse-event counts. It does not support reconstruction of inferential analyses or a claim that particular statistical methods were used.

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("ETBX-011 in Combination With ALT-803")
n      <- c(3)
events <- c(1)
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  ETBX-011 in Combination With ALT-803  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. Multiplicity arises when several outcomes, comparisons, time points, or statistical tests are examined: the chance of at least one apparently notable result can increase as the number of tests grows. In general, prespecified priorities and an adjustment strategy can help readers understand how multiple findings were interpreted. No such plan is reported for this study.

The primary outcome is the number of participants with dose-limiting toxicities over 9 weeks. Duration of Response, Progression Free Survival, and Overall Survival are listed as secondary outcomes. Their listing does not establish that they were analyzed, and no results or multiplicity procedures are reported. The number of analyses is recorded as 0. It is therefore not possible to determine whether any planned tests were performed, whether analyses were omitted, or whether outcome priorities changed.

Missing-data handling is also not reported in the registry record. There is no description of withdrawals, incomplete follow-up, censoring, imputation, or sensitivity analyses. This matters because a participant who was not observed for the full endpoint timeframe may not have the same opportunity for an event to be recorded as a participant with complete follow-up. The record does not say whether anyone had incomplete observation.

Analysis populations are not described. It is not reported whether outcome summaries were intended to include all enrolled participants, only those who received treatment, or a subset with evaluable follow-up. The adverse-event at-risk counts are listed, but they do not establish the population used for the primary endpoint or secondary outcomes. Without these definitions, the scope of any outcome estimate cannot be assessed.

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 non-serious adverse event terms

The registry lists one intervention group, ETBX-011 in Combination With ALT-803. For serious adverse events, 3 participants were at risk and 0 were affected; deaths are listed as 0. For other adverse events, 3 participants were at risk and 3 were affected. These are participant counts, not a complete accounting of event types or event episodes.

The record does not list serious adverse-event terms, and the specific other adverse events are not reported in the registry record. It also does not provide severity grades, timing, duration, attribution to study treatment, or follow-up detail. The figures therefore describe only the recorded counts in the at-risk group; they do not explain what events occurred or how they were assessed.

Zero participants affected by serious adverse events in this small group is a descriptive observation, not proof that serious events cannot occur. Likewise, the count for other adverse events does not establish their cause or clinical importance. These safety summaries are distinct from the primary endpoint, which concerns dose-limiting toxicities over 9 weeks; its result is not reported in the registry record.

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

The record establishes that a phase 1b/2 sequential dose-escalation study of ETBX-011 with ALT-803 was registered for people with CEA-expressing cancers. It identifies the primary safety outcome as the number of participants with dose-limiting toxicities during 9 weeks, lists three secondary outcomes, reports enrollment of 3, and gives limited adverse-event counts. It also records the study as terminated.

Those details do not establish the result of the primary outcome. No dose-limiting-toxicity count, analysis, or estimate of uncertainty is reported. The adverse-event figures do not fill that gap: they concern serious and other adverse events, and the registry does not report their terms or relationship to the primary endpoint. The reason for termination is also not reported, so termination should not be interpreted as evidence of a particular safety or efficacy finding.

The record does not establish whether the combination is more effective or safer than another treatment. No concurrent comparator is identified, and the study is not listed as randomized. A treated-group observation without a control cannot separate a treatment effect from other possible explanations. The registry also does not report results for Duration of Response, Progression Free Survival, or Overall Survival.

In general, early-phase dose-escalation research can provide information about safety and tolerability in the studied setting. The available registry record is too limited to characterize dose-limiting toxicity, select a dose, or assess efficacy. The findings should be read as a sparse record of a small terminated study, not as evidence for or against treatment benefit.

14. Why This Trial Matters Statistically

This study raises statistical issues that are common in early-phase clinical research. A dose-escalation design has a different purpose from a randomized efficacy trial: it can focus on safety and tolerability as participants receive treatment at successive dose levels. The primary outcome reflects that focus by counting participants with dose-limiting toxicities within a stated timeframe. Interpreting such an endpoint requires the toxicity definition, dose information, and follow-up completeness, none of which is reported in the registry record.

The record also illustrates why study design and reported results must be read together. It identifies a sequential model, no masking, and allocation as NA, but no control arm. A single-group study may describe what happened among enrolled participants, yet it cannot provide a direct treatment contrast. This distinction is important when a study’s stated aims include efficacy as well as safety.

Reporting matters just as much as design. The primary endpoint is named, but its outcome and analysis are absent. The registry lists secondary outcomes without results and gives only limited adverse-event counts. Without outcome estimates, analysis populations, uncertainty measures, and missing-data information, readers cannot assess the magnitude or precision of the findings.

Finally, a terminated status is an important part of the record, but its meaning depends on the reason and circumstances. Those details are not reported. Avoiding an assumed explanation is essential: the status alone does not show why the study ended or what its results were. Statistically, the key lesson is that a protocol question, an observed count, and a comparative treatment effect are different kinds of information.

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 most immediate limitation is the absence of reported primary-outcome results. Although the endpoint and its 9-week timeframe are identified, the count of participants with dose-limiting toxicities is not reported. The record also omits the definition of a dose-limiting toxicity and the dose levels used, limiting interpretation of the endpoint’s intended meaning.

Enrollment was 3, and the study has no listed concurrent control group. The design therefore offers no randomized treatment contrast. The registry does not report participant-level outcomes, follow-up completeness, or analysis populations, so it is not possible to tell who contributed to each outcome or whether observations were incomplete.

The study is recorded as terminated, but the reason is not reported in the registry record. The record also omits the dose-escalation rules, treatment exposure details, protocol changes, interim analyses, and statistical analysis plan. None of these omissions can be resolved from the listed status or design labels.

Safety reporting is limited to counts: serious adverse events affected 0 of 3 at risk, other adverse events affected 3 of 3 at risk, and deaths were 0. Specific event terms, severity, timing, and attribution are not reported. The listed secondary outcomes have no reported results. Taken together, these limitations prevent detailed assessment of safety, efficacy, precision, and the reasons the study ended.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: QUILT-3.040: ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D)) Vaccine in Combination With ALT-803 (Super-agonist IL-15) in Subjects Having CEA-Expressing Cancer — NCT03127098.
• Registry record last updated 2024-08-06; status last verified 2019-08.
• Results first posted 2024-08-06.
• 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

NCT03127098 is a phase 1b/2 study of ETBX-011 in combination with ALT-803 in people with CEA-expressing cancers. It is described as a sequential dose-escalation study, with allocation recorded as NA and masking as none. Enrollment was 3, and the study status is terminated.

The primary outcome is the number of participants with dose-limiting toxicities over 9 weeks. Duration of Response, Progression Free Survival, and Overall Survival are listed as secondary outcomes. No analyses or outcome results are reported in the registry record.

For the combination group, 3 participants were at risk for serious adverse events and 0 were affected; 3 were at risk for other adverse events and 3 were affected. Deaths are listed as 0. The reason for termination, specific adverse-event terms, and statistical analysis details are not reported in the registry record.