A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803 in Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803 in Patients With Advanced Solid Tumors (NCT01946789), a non-randomized phase 1 study. The primary outcome is Dose Limiting Toxicity.

2. Clinical Question

This design focuses on safety during dose escalation, alongside clinical and immunologic effects. It is not designed as a randomized comparison of ALT-803 against a control intervention. Differences between dose groups cannot be interpreted as treatment effects because dose, route, and the patients in each group may differ, and the registry does not describe random allocation.

The registry lists secondary outcomes concerning anti-drug antibodies, pharmacokinetics, interferon gamma, and objective response rate. These outcomes broaden the study’s descriptive scope, but their presence does not establish that the record reports results for them. Results for the primary endpoint and these secondary outcomes are not reported in the registry record.

3. Trial Design

This is a Phase 1, open-label, multicenter, non-randomized dose-escalation study of ALT-803 in patients with surgically incurable advanced solid tumors. The registry lists an enrollment of 26 and identifies a single-group overall model, while also listing groups that differ by dose and route. The listed schedules include intravenous dosing, subcutaneous dosing, and intratumoral dosing followed by subcutaneous dosing.

Because the study is open-label, masking is listed as none. Because allocation is non-randomized, the dose groups do not serve as randomized treatment and control arms. They represent different exposure schedules within a dose-escalation study. Comparisons between them may be affected by differences in dose, route, patient characteristics, or the order and circumstances under which groups entered the study; the registry record does not provide enough detail to assess these possibilities.

The primary endpoint is dose-limiting toxicity, with the registry defining the safety endpoint in terms of the MTD and a DLT threshold. Its stated timeframe is 9 months. The record describes the study as completed and lists a start of 2014-05 and a primary completion of 2017-08. These dates describe the registry timeline, not the timing of any individual participant’s assessments.

Registered secondary outcomes include anti-drug antibodies to ALT-803; pharmacokinetic measures, including half-life, Tmax, Cmax, and AUC measures; interferon gamma; and objective response rate. The registry record does not describe the schedule of assessments, the detailed dose-escalation rules, or how participants moved between doses. Those design details are not 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.

Only the first 6 of 9 groups are shown.

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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Dose Limiting Toxicity, measured over 9 months.

The primary endpoint is dose-limiting toxicity, expressed as a count of participants. The registry defines the safety endpoint as the MTD of ALT-803: the dose level below that at which at least 2 of 6 patients experience a DLT. The endpoint timeframe is 9 months.

In general, a DLT endpoint is used in early-phase dose-escalation research to characterize safety at different dose levels. The MTD definition gives a decision threshold based on observed toxicities; it is not, by itself, a measure of antitumor benefit. The definition also makes the threshold dependent on what the study classifies as a DLT and how those events are assessed. The registry record does not report the detailed DLT criteria or the observed number of participants with DLTs at each dose level.

The registry’s definition should not be confused with the serious adverse-event counts. Serious adverse events and DLTs are distinct reporting concepts, and the record does not identify the serious adverse-event counts as DLT counts. Nor does the endpoint description report an MTD result. The primary endpoint result is not reported in the registry record, so the stated definition alone does not establish which dose, if any, met the study’s MTD criterion.

For interpretation, the endpoint is best understood as a planned safety measure with a stated threshold and timeframe. It does not provide a basis for judging efficacy, and the record does not provide enough information to independently reproduce the endpoint classification.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the study as Phase 1, open-label, non-randomized, and dose-escalating. Those design features determine how the posted numbers should be read. The data are descriptive by dose and route group; the registry does not identify a randomized control arm or a planned between-group causal comparison. No statistical analyses are listed in the registry record.

What does a non-randomized dose comparison show?

In general, randomization helps make comparison groups similar, on average, with respect to factors that can affect an outcome. Here, allocation is listed as non-randomized, and the groups correspond to different dose levels or routes. Their observed event counts can describe what was recorded in each group, but they cannot isolate a dose effect from other differences between groups. This limitation applies even when a numerical contrast appears large or small; the registry record does not report an adjusted analysis to address such differences.

The listed groups include N-803 IV 0.3/0.5 ug/kg, N-803 IV 1.0 ug/kg, N-803 IV 3.0 ug/kg, N-803 IV 6.0 ug/kg, N-803 Subcutaneous 6.0 ug/kg, N-803 Subcutaneous 10.0 ug/kg, N-803 Subcutaneous 15.0 ug/kg, N-803 Subcutaneous 20.0 ug/kg, and N-803 Intratumoral 10.0 ug/kg followed by N-803 15.0 ug/kg Subcutaneous. The intervention is identified as ALT-803. The record does not explain the naming difference between ALT-803 and N-803 in the intervention and group descriptions.

What does the primary endpoint definition mean?

The primary endpoint is a participant count for dose-limiting toxicity, and the stated safety endpoint is the MTD. Its definition uses a threshold of at least 2 of 6 patients experiencing a DLT at a dose level. In general, such a threshold is a rule for interpreting observed toxicity during dose escalation; it is not a guarantee that the selected dose has a particular safety profile in a broader population. The registry record does not report the observed DLT counts, the MTD determination, or the detailed rules used to classify a DLT.

The stated endpoint timeframe is 9 months. A timeframe identifies the period associated with the outcome as registered; it does not, on its own, tell readers how often assessments occurred or how incomplete follow-up was handled. Those details are not reported in the registry record.

How should adverse-event counts be interpreted?

The posted safety information separates participants with serious adverse events from those with other adverse events, and also gives a death count for each group. These are counts, not comparative effect estimates. In general, a count is easier to interpret when its denominator, event definition, observation period, and handling of repeat events are clear. The record gives numbers at risk for the serious and other event categories, but it does not provide further detail about event collection or attribution. The serious adverse-event terms listed in the record each have a frequency of 33.3%; the denominator for those term percentages is not reported in the registry record.

Serious adverse events should not be equated with DLTs. A serious-event classification and a protocol-defined dose-limiting toxicity endpoint can represent different criteria. The registry does not state which serious events, if any, met the DLT definition. The death counts likewise do not establish cause or relationship to the intervention because attribution is not reported.

What can confidence intervals and tests add?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure and its assumptions. It helps communicate precision; it does not remove bias from a non-randomized comparison or correct incomplete data. A hypothesis test addresses a specified statistical question under a model, but its result does not establish clinical importance by itself. No confidence intervals, test statistics, or p-values for the clinical outcomes are reported in the registry record, and the statistical analysis plan is not reported.

The registry’s sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are illustrations rather than the trial’s own design or observed power. The record does not report a trial sample-size justification. In addition, the study’s registered design is non-randomized and dose-escalating, so an equal-allocation, two-arm illustration should not be mistaken for a description of its actual group allocation.

Why does dose escalation limit precision?

In general, small groups yield limited information about how frequently uncommon outcomes occur. A count in a group can be informative as a record of observed events but may be imprecise as an estimate of event frequency. The group counts and denominators should be read together, without treating the groups as interchangeable or adding them into a combined rate. No pooled primary endpoint estimate is reported in the registry record.

For outcomes such as pharmacokinetic measures, a statistical analysis would need to specify how measurements were summarized and how incomplete observations were handled. For a binary outcome such as objective response, the analysis would need to define the response criteria and analysis population. The registry lists the outcomes but does not report these analysis details or results. Thus, explanations of intervals, tests, and modeling above are general statistical context, not descriptions of analyses reported for this study.

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("N-803 IV 0.3/0.5 ug/kg", "N-803 IV 1.0 ug/kg", "N-803 IV 3.0 ug/kg", "N-803 IV 6.0 ug/kg", "N-803 Subcutaneous 6.0 ug/kg", "N-803 Subcutaneous 10.0 ug/kg")
n      <- c(2, 3, 3, 3, 3, 3)
events <- c(0, 0, 0, 0, 0, 0)
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  N-803 IV 0.3/0.5 ug/kg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  N-803 IV 1.0 ug/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  N-803 IV 3.0 ug/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  N-803 IV 6.0 ug/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  N-803 Subcutaneous 6.0 ug/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  N-803 Subcutaneous 10.0 ug/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes: anti-drug antibodies to ALT-803; pharmacokinetic half-life and Tmax; Cmax; AUC 0-t, AUC0-24, and AUC0-infinity; interferon gamma; and objective response rate. Considering many outcomes can raise a multiplicity issue: in general, the more statistical questions tested, the greater the chance of finding an apparently notable result by chance if no adjustment or prespecified hierarchy is used. The registry record does not report whether multiplicity was addressed, how outcomes were prioritized, or which analyses were prespecified.

No statistical analyses are listed in the registry record. The analysis plan, outcome-specific estimates, uncertainty measures, and test results are not reported. This means the record does not show whether the primary endpoint was analyzed as planned or whether secondary outcomes were treated as exploratory. It is not possible to infer a testing strategy from the outcome titles alone.

Missing-data handling is also not reported. In general, incomplete follow-up or unavailable measurements can affect the interpretation of event counts and estimates, particularly if the likelihood of missingness is related to health status or outcome. The registry does not describe reasons for missing observations, imputation methods, censoring rules, or sensitivity analyses. It also does not report analysis populations, such as which participants were included in each endpoint analysis.

The enrollment figure does not resolve these gaps: it does not establish how many participants contributed data to each outcome or how many had complete follow-up. The posted record therefore permits a description of registered outcomes and safety counts, but not a full assessment of multiplicity, missingness, or analysis-population choices.

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: disease progression (33.3%), muscular weakness (33.3%), metastases to central nervous system (33.3%), headache (33.3%), haematuria (33.3%).

The registry reports serious adverse events, other adverse events, and deaths by listed group. For serious adverse events, the affected and at-risk counts are: N-803 IV 0.3/0.5 ug/kg, 0 of 2; N-803 IV 1.0 ug/kg, 1 of 3; N-803 IV 3.0 ug/kg, 1 of 3; N-803 IV 6.0 ug/kg, 1 of 3; N-803 Subcutaneous 6.0 ug/kg, 0 of 3; N-803 Subcutaneous 10.0 ug/kg, 1 of 3; N-803 Subcutaneous 15.0 ug/kg, 2 of 4; N-803 Subcutaneous 20.0 ug/kg, 2 of 3; and N-803 Intratumoral 10.0 ug/kg followed by N-803 15.0 ug/kg Subcutaneous, 0 of 2.

For other adverse events, the record lists every participant at risk in each group as affected. Death counts by group are 0, 2, 1, 1, 1, 1, 3, 1, and 2, respectively, in the order. These counts do not establish cause or relationship to ALT-803. The record lists disease progression, muscular weakness, metastases to central nervous system, headache, haematuria, and dyspnoea among the top serious terms, each at 33.3%; the denominator for those percentages is not reported in the registry record.

These are descriptive safety figures, not DLT results or randomized comparisons. Event attribution and the relationship between serious events and the primary endpoint are not reported.

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

The registry record establishes that this was a completed Phase 1, open-label, non-randomized dose-escalation study of ALT-803 in patients with advanced solid tumors. It records the planned DLT endpoint, dose and route groups, secondary outcomes, and adverse-event counts. Those details describe the study and the posted observations; they do not provide a complete account of the results.

The record does not report the primary endpoint result, an MTD determination, or the DLT counts used to assess the stated threshold. The serious adverse-event counts cannot fill that gap because the registry does not identify them as DLTs. The listed deaths are not accompanied by attribution or cause, so they do not establish that ALT-803 caused them. Similarly, the secondary outcome titles do not show whether pharmacokinetic, immunologic, or response outcomes were observed or what their values were.

The non-randomized dose groups are not a like-for-like control comparison. Differences in observed counts between those groups cannot be interpreted as causal effects of dose or route. The small group denominators also mean that the counts describe the participants recorded in each group, rather than establishing a precise underlying event rate. The registry does not report confidence intervals or other measures of uncertainty for the clinical outcomes.

In general, early-phase dose-escalation studies can provide descriptive safety and pharmacology information that informs later research. That general role does not establish what this study found. The registry record does not report enough outcome data or analysis detail to assess the magnitude, precision, or clinical meaning of any safety, immunologic, pharmacokinetic, or response result. No conclusion that ALT-803 is effective or ineffective follows from the information reported in the registry.

14. Why This Trial Matters Statistically

This study is statistically notable as a non-randomized dose-escalation design with groups defined by both dose and route. That structure makes careful separation of description from comparison essential. Group-level event counts can document what was observed, but they do not support a randomized contrast or isolate the effect of changing dose or route. The registry itself warns that the arms are not a like-for-like control comparison.

The primary endpoint is framed around a DLT threshold and an MTD, a form of safety question suited to early-phase dose escalation. The distinction between that endpoint and the separately posted serious adverse-event counts matters: the registry does not equate the two, and the serious-event figures cannot substitute for the missing DLT result. This is a useful example of why endpoint definitions need to be read alongside the specific results reported for those endpoints.

The study also registered clinical and immunologic outcomes, including pharmacokinetic measures, interferon gamma, anti-drug antibodies, and objective response rate. Such a broad set of outcomes can generate several distinct statistical questions. Without a reported analysis plan, multiplicity approach, estimates, and uncertainty measures, readers cannot tell how those questions were prioritized or evaluated.

Finally, the record illustrates the difference between a completed study and a complete statistical results account. Completion status and enrollment do not reveal endpoint-specific denominators, missing-data handling, or analysis populations. A more complete interpretation would require the primary DLT results, the MTD determination, secondary outcome results, and relevant analysis details, none of which are reported in the registry record.

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 leaves important trial-specific details unavailable. It describes the study as open-label and dose-escalating, but does not report the detailed escalation rules, the criteria used to define a DLT, or how an MTD was selected from observed outcomes. Although the primary endpoint timeframe is 9 months, assessment schedules and the handling of incomplete follow-up are not reported.

The record lists dose and route groups but does not report group-level baseline characteristics or explain how participants were allocated among them. The groups are non-randomized and are not like-for-like controls. Any apparent differences in adverse-event counts may reflect factors other than dose or route, and the record does not provide an adjusted comparative analysis.

The primary endpoint result and DLT counts are not reported. Serious adverse-event counts and deaths are available, but the record does not provide attribution, causes of death, or the relationship of these events to the DLT endpoint. The denominator used for the listed 33.3% serious-event term frequencies is also not reported in the registry record.

The registry lists secondary outcome topics but does not report their results, endpoint-specific denominators, or analysis methods. It does not report a statistical analysis plan, multiplicity procedures, missing-data methods, confidence intervals, or analysis populations. These omissions limit assessment of the precision, completeness, and interpretation of the posted information. The sample-size assumptions are described as planning illustrations, not the trial’s own design; a trial sample-size justification is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803 in Patients With Advanced Solid Tumors — NCT01946789.
• Registry record last updated 2025-01-22; status last verified 2025-01.
• Results first posted 2025-01-22.
• 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 describes NCT01946789 as a completed Phase 1, open-label, multicenter, non-randomized dose-escalation study of ALT-803 in advanced solid tumors. The listed population includes patients with surgically incurable melanoma, renal cell, non-small cell lung, and squamous cell head and neck cancer. Enrollment is 26. The groups cover intravenous, subcutaneous, and intratumoral dosing schedules.

The primary safety endpoint is dose-limiting toxicity, with an MTD definition based on the dose level below that at which at least 2 of 6 patients experience a DLT; the timeframe is 9 months. Secondary outcomes include anti-drug antibodies, pharmacokinetic measures, interferon gamma, and objective response rate. The record reports adverse-event counts by group but does not report the primary endpoint result, an MTD determination, secondary outcome results, or the statistical analysis plan.