AUY922 for Advanced ALK-positive NSCLC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AUY922 for Advanced ALK-positive NSCLC (NCT01752400), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

In practical terms, the study was designed to describe response and safety in a specific clinical setting: advanced ALK-rearranged NSCLC after acquired resistance to prior ALK tyrosine kinase inhibition. It was not designed, as recorded, to estimate a treatment effect relative to a concurrent control. That distinction matters when interpreting any event counts: without a comparator, changes cannot be attributed to AUY922 by comparing outcomes across randomized groups. The registry lists Massachusetts General Hospital as sponsor and marks the study completed. It reports enrollment of 6.

3. Trial Design

The registry classifies this study as Phase II, open-label, and single-group. Allocation is recorded as NA, and masking is listed as none. Participants received AUY922; no comparator arm is listed. Consequently, the design can describe outcomes among the enrolled participants but cannot make a randomized comparison between AUY922 and another treatment.

The intervention was AUY922 by intravenous infusion on Days 1, 8 and 15 of each 21 day cycle. Each infusion lasted approximately 60 minutes. The registry’s primary endpoint was objective response, defined as the number of participants with a complete response or partial response by RECIST v1.1. Assessment was scheduled at baseline and then every six weeks (± 7 days), until disease progression. The registry gives this timeframe but does not report the observed primary endpoint count.

The study is marked completed. The recorded start is 2013-01, and primary completion is recorded as 2017-06. Enrollment is 6. The registry lists progression-free survival, disease control rate, adverse events, concurrent KRAS mutations, ALK translocation variant type, ALK mutation status, and median overall survival as secondary outcomes. Those outcome names describe what was registered; they do not establish that results for each outcome are available in the posted record.

The registry record does not report a sample-size justification, a detailed statistical analysis plan, or an interim-analysis plan. It also does not report enough information to reconstruct participant flow, treatment exposure, or analysis populations. The design classification and the posted counts should therefore be read as a limited account of a small, uncontrolled study, rather than as a basis for a comparative efficacy estimate.

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 Objective Response Rate, measured over Baseline and then every six weeks (± 7 days), until the time of disease progression.

The primary endpoint is objective response rate, expressed in the registry as a count of participants. It includes participants assessed as having either a complete response (CR) or a partial response (PR) under RECIST v1.1. A complete response is defined as disappearance of all target lesions, with any pathological lymph node reduced to less than 10 mm in short axis. A partial response requires at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference.

Objective response is used in oncology trials to describe measurable tumor shrinkage according to specified criteria. Applying a common response definition makes assessments more systematic than relying on an unstructured impression of change. The registry’s schedule calls for assessment at baseline and then every six weeks (± 7 days), until disease progression.

This endpoint captures whether a participant meets the response criteria; it does not, by itself, describe how long a response lasts, how long participants remain progression-free, or overall survival. The registry lists those as separate secondary outcomes. The observed number achieving CR or PR is not reported in the registry record, so the primary endpoint cannot be quantified from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The primary endpoint is a count: participants who achieved either a complete response or a partial response by RECIST v1.1. The complete- and partial-response definitions specify how lesion changes qualify. In general, a prespecified endpoint helps keep the outcome being evaluated consistent with the question a trial set out to address. Here, the registry gives the definition and assessment schedule, but it does not report the observed response count. A count alone would also need its analysis population and handling of missing assessments to be interpreted fully; those details are not reported in the registry record.

What can a single-group study estimate?

In general, a single-group study can summarize outcomes observed among its participants. It has no concurrent randomized group for estimating how outcomes might differ under another treatment or under a control condition. Randomization is useful because it supports comparisons between groups while reducing systematic differences in participant characteristics. With no comparator listed, the registry’s design cannot provide that kind of treatment contrast. Descriptive outcomes, when reported, should not be presented as proof that the intervention caused them.

What does a confidence interval mean?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used. It helps readers distinguish a precise estimate from one that is compatible with a wider range of values. The registry record does not report a confidence interval for the primary response endpoint. Without the response result and an uncertainty estimate, the precision of the primary outcome cannot be assessed from the posted record.

Why do event counts need context?

For a binary outcome such as whether a participant experienced an event, the count describes how many participants met the event definition within the group considered. Interpretation depends on the denominator, outcome definition, observation period, and analysis population. The registry’s safety fields give at-risk and affected counts, but the record does not provide fuller details about event collection, exposure duration, or how the safety population was defined. These counts should not be interpreted as comparative rates against another group.

What is the role of statistical significance?

In general, a significance test evaluates how compatible data are with a specified null hypothesis under a statistical model. A p-value is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. The registry record lists no analysis entries for this study and does not report a primary endpoint test or p-value. No significance conclusion can therefore be drawn from the listed primary outcome information.

How should the planning illustration be read?

The registry’s sample-size assumptions describe a planning illustration computed from the observed effect, rather than the trial’s own design. The stated 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 non-time-to-event outcomes, the illustration is expressed as participants per arm for 80% or 90% power; time-to-event illustrations use total events. These are planning quantities, not observed trial results and not observed power. The trial itself is recorded as single-group, so the hypothetical equal allocation between two arms in the planning assumptions does not describe the trial’s registered design. The registry record does not report a sample-size justification for the study.

General methods such as confidence intervals and significance tests can help quantify uncertainty when estimates and analysis details are available. In this record, the primary response count and its analysis are not reported. Statistical interpretation must therefore stay with what is documented: the endpoint definition, study design, enrollment, and the listed safety counts. No new estimate can be reconstructed from the record without adding assumptions or data that are not reported.

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("AUY922")
n      <- c(6)
events <- c(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  AUY922  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including progression-free survival, disease control rate, adverse events, ALK and KRAS characteristics, and median overall survival. When a study evaluates multiple outcomes, general statistical practice considers whether and how to address multiplicity: testing many outcomes can increase the chance of obtaining a seemingly notable result by chance. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting these outcomes. It also lists no analysis entries, so there are no posted outcome analyses from which to assess how multiple outcomes were handled.

Missing-data methods are not reported in the registry record. The primary endpoint requires response assessment, but the record does not state how missing or unevaluable assessments were classified, whether participants without an assessment were included in the analysis, or whether any imputation method was used. These choices can affect a response count and its interpretation. They should not be inferred from the endpoint definition or assessment schedule alone.

The registry record does not report the analysis populations, such as which participants were included in each endpoint analysis, or the participant flow from enrollment through assessment. Enrollment is listed as 6, but the primary response result and its denominator are not reported. Safety fields do identify the at-risk counts for the listed event categories; that does not establish the analysis population used for other outcomes.

As a result, the available record does not establish how multiplicity, missing assessments, or analysis-population decisions were handled. Those omissions limit reproducibility and the ability to judge whether the posted findings, where available, reflect prespecified analyses.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (16.7%), neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, progressive disease (16.7%).

The registry’s safety fields list 6 participants at risk for serious adverse events, with 2 affected. For other adverse events, the record lists 6 at risk and 6 affected. It also lists 1 death. These figures are counts from the registry record; they do not show a comparison with another group and do not, by themselves, establish that an event was caused by AUY922.

The serious adverse event terms listed are abdominal pain and neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, progressive disease. Each term is recorded as 16.7%. These percentages are reported as listed and should be read alongside the small at-risk group. The registry record does not provide further details about event timing, duration, severity grades, relatedness assessments, or whether the listed terms represent unique participants.

Serious adverse events and other adverse events are distinct safety categories in the registry fields. The affected counts should not be combined, and the death count should not be assumed to be a count of deaths caused by the intervention. The posted figures provide a limited descriptive safety account, not a comparative estimate of risk.

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

The registry record establishes that a completed Phase II, open-label, single-group study evaluated AUY922 in advanced ALK-rearranged NSCLC with acquired resistance to prior ALK tyrosine kinase inhibition. It defines objective response using RECIST v1.1 and describes when assessments were scheduled. It also reports enrollment and selected safety counts. These details explain the study’s scope and the kind of outcome it was intended to measure.

The record does not report the observed primary response count or an analysis of that endpoint. Therefore, it does not allow the reader to determine from the posted results how many participants achieved a complete or partial response, or how precisely an estimate of response was measured. The absence of a reported response result is not evidence of either response or no response.

The single-group design also means that any descriptive outcome would not establish what would have happened under a different treatment or control condition. The record does not contain a randomized comparison, and no like-for-like control arm is listed. The safety counts similarly do not quantify relative risk or prove causation.

In general, a response endpoint is one part of a broader assessment. It does not substitute for duration of response, progression-free survival, overall survival, or a comparative evaluation of safety. The registry lists some of these as secondary outcomes, but their names alone do not communicate results. Those results and their analysis details are not reported in the registry record summarized in the available information.

The appropriately limited conclusion is that the record describes a small, uncontrolled study and its planned response measure, while the primary response result and important analysis details are not reported. The posted safety figures are descriptive. They cannot answer comparative or causal questions on their own.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly defined primary endpoint and the absence of a reported primary result in the registry record. Objective response is defined using RECIST v1.1, and the assessment schedule is specified. Yet the observed count and its precision are not reported. This illustrates why an endpoint definition alone is not enough to interpret a trial: readers also need the actual outcome and information about how it was analyzed.

The single-group design is another important feature. Without random allocation to a concurrent comparator, the study can describe outcomes in its participants but cannot estimate a randomized difference between treatment strategies. This distinction applies even when the endpoint is objective and the assessment criteria are standardized. A standardized measurement does not remove the limitations of an uncontrolled comparison.

The registry lists enrollment of 6, making the safety figures and any eventual outcome estimates especially sensitive to individual observations. Counts can be useful for describing what was recorded, but small-group counts should not be mistaken for stable estimates of outcomes in a broader population. The record’s selected safety terms are descriptive and do not establish comparative harm or causation.

Finally, the registry lists several secondary outcomes but does not report analysis entries, multiplicity handling, missing-data methods, or analysis populations. These details affect how confidently readers can interpret findings and whether an analysis can be reproduced. The trial is a useful example of why design, outcome reporting, and analytic transparency all matter alongside endpoint definitions.

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 identifies the study as single-group, open-label, and unmasked, with no comparator listed. Consequently, there is no randomized control comparison to support a treatment-effect contrast. The record also reports enrollment of 6, so descriptive results would be based on a small group and could be strongly influenced by individual observations.

The primary objective-response count is not reported in the registry record, and the registry lists no analysis entries. The record therefore does not provide an estimate or uncertainty interval for the primary endpoint. It also does not report analysis populations, participant flow, missing-data handling, or a detailed statistical analysis plan. These omissions prevent a full assessment of how eligible participants and unevaluable assessments were handled.

Although several secondary outcomes are listed, their outcome results and the approach to multiplicity are not reported in the registry record. The safety information is limited to at-risk and affected counts, deaths, and named serious adverse event terms with percentages. Further event-level context, including timing and relatedness, is not reported in the registry record.

The record describes the intervention schedule and the primary assessment timeframe but does not provide information sufficient to evaluate treatment exposure or adherence. It also does not report a sample-size justification, interim-analysis plan, or protocol details beyond those stated. These limitations constrain both the statistical interpretation and the degree to which the study can be independently assessed from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: AUY922 for Advanced ALK-positive NSCLC — NCT01752400.
• Registry record last updated 2018-03-29; status last verified 2018-03.
• Results first posted 2018-03-29.
• 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 lists NCT01752400 as a completed Phase II study sponsored by Massachusetts General Hospital. The recorded start is 2013-01, and primary completion is 2017-06. Enrollment is 6.

The study was open-label and single-group, with AUY922 given by intravenous infusion on Days 1, 8 and 15 of each 21 day cycle. Its primary endpoint was the number of participants achieving complete or partial response by RECIST v1.1. The registry record does not report the observed primary response count or an analysis of that endpoint.

Safety fields list serious adverse events in 2 of 6 participants at risk, other adverse events in 6 of 6 at risk, and 1 death. These are descriptive figures, with no randomized comparator listed. The record does not report analysis populations, missing-data methods, or a multiplicity approach.