Etirinotecan Pegol (NKTR-102) in NSCLC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Etirinotecan Pegol (NKTR-102) in NSCLC (NCT01773109), a na phase 2 study. The primary outcome is Overall Objective Response Rate.

2. Clinical Question

The clinical question is descriptive rather than a randomized comparison. The study aimed to estimate response in a specific treatment setting: metastatic or recurrent NSCLC after failure of second-line therapy. The intended response measure combines complete and partial responses, so the outcome concerns tumor response as defined by the stated criteria, not survival, symptom change, or a comparison with another treatment.

The registry lists an enrollment of 40, while the brief summary says up to 37 eligible subjects would receive the investigational drug. Those statements describe different enrollment and eligibility details; the record does not explain the distinction. Nor does it report how many participants were included in the primary endpoint analysis. Without the response count and analysis population, the objective response rate cannot be read from this record.

3. Trial Design

This was a Phase 2, single-group, open-label study of etirinotecan pegol in patients with metastatic or recurrent NSCLC after failure of second-line treatment. The registry lists allocation as not applicable and masking as none. Consequently, the design has no randomized control group and does not support a like-for-like comparison between treatment arms. Its stated primary purpose was to estimate objective response.

The registry records enrollment of 40. The brief summary says up to 37 eligible subjects would receive treatment, and the arm description gives a dose of 145 mg/m2 intravenously every 3 weeks. The brief summary also describes continued dosing until subjects were no longer benefiting. The registry record does not clarify how many enrolled participants met eligibility criteria, received treatment, or contributed to the primary outcome.

The primary outcome is Overall Objective Response Rate, measured as a count of participants with complete response or partial response according to RECIST version 1.1. The stated timeframe is 6 weeks. The registry lists one outcome measure and no analyses. It does not report an observed response count, an estimated response rate, an uncertainty interval, or a statistical test for that outcome.

The study is marked completed. Its recorded start is 2013-01 and its primary completion is 2016-01. Abramson Cancer Center at Penn Medicine is listed as the sponsor. The registry record does not report the protocol’s sample-size justification, interim monitoring plan, or detailed statistical analysis plan. The presence of enrollment information alone does not establish how the target enrollment was chosen or whether the planned analysis was carried out as intended.

Because treatment was administered in a single group without masking, the design can describe outcomes among treated participants if those outcomes are reported, but it cannot isolate a treatment effect from other explanations using a concurrent randomized comparison. The treatment setting and eligibility criteria also define the population to which any observed response estimate would apply.

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 Overall Objective Response Rate, measured over 6 weeks.

The primary endpoint is Overall Objective Response Rate, defined as the number of participants with a complete response or partial response measured by RECIST version 1.1. The registry describes the outcome as a participant count, with a timeframe of 6 weeks. Although the endpoint title uses “rate,” the posted primary outcome information identifies a count; the record does not provide the response count or a calculated rate.

Objective response is used to summarize whether participants meet stated criteria for complete or partial tumor response. In general, a response endpoint can provide a direct measure of tumor shrinkage under specified assessment criteria. It is distinct from outcomes such as duration of response, progression-free survival, overall survival, symptoms, or quality of life. Those outcomes are not identified as the primary endpoint in this record.

The timeframe matters because response is evaluated at a defined point or period. The record gives 6 weeks but does not describe assessment schedules, confirmation requirements, handling of assessments outside that timeframe, or the endpoint analysis population. Those details are not reported in the registry record.

For interpretation, an estimated response proportion would need both a response numerator and an analysis denominator. Neither is stated for the primary outcome. The enrollment number and the number at risk in the safety record cannot substitute for a documented endpoint denominator. Thus, the endpoint’s definition is available, but its observed value and precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a response count represent?

In general, a binary endpoint classifies each participant into one of two outcome categories, such as meeting or not meeting a prespecified response definition. A participant count records how many fall into the response category. A response rate expresses that count relative to a defined group of participants. For a rate to be interpretable, the numerator and denominator need to refer to the same endpoint definition and analysis population.

In this study, the registry identifies complete response or partial response by RECIST version 1.1 as the response definition. The primary outcome is recorded as a participant count, with a timeframe of 6 weeks. The number meeting the definition and the number included in the analysis are not reported in the registry record. Thus neither the response count nor the rate can be stated. The total enrollment of 40 does not establish the primary endpoint denominator.

Why does an uncertainty interval matter?

In general, a confidence interval describes the range of values that are reasonably compatible with the observed data under a specified statistical procedure. It communicates precision, not whether a result is clinically important, unbiased, or caused by a treatment. Estimates based on fewer observations tend to be less precise than estimates based on more observations, although the actual precision also depends on the observed outcomes and the method used.

No uncertainty interval or primary endpoint analysis is reported in the registry record. The response result therefore cannot be assessed for statistical precision. A numerical response estimate without its denominator and uncertainty would also leave important context missing.

What is the role of the study design?

In general, a single-group study describes outcomes in participants who receive the study intervention. Without a concurrent comparison group, observed outcomes cannot be contrasted with outcomes under another assigned treatment within the same study. Differences from expectations or from results in other populations can reflect differences in participants, assessment, follow-up, or other factors as well as any treatment effect.

This study is recorded as single-group, open-label, with allocation not applicable and no masking. Those design details define what the study can address. Its stated primary objective is to estimate objective response, not to test a randomized treatment contrast. The registry record does not report an adjustment plan or other methods that would support a causal comparison.

How should planning illustrations be read?

In general, sample-size calculations describe how many observations might be needed under specified assumptions for a planned analysis. A calculation is not an observed result, and it does not establish the probability that a completed study detected an effect. “Observed power” is not a substitute for reporting an effect estimate and its precision.

The planning assumptions associated with the statistical material specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe planning illustrations, not the design of this single-group trial. The assumed effect is expressed as a stated fraction of an observed effect, but the registry record does not report the primary response result needed to assess that basis. The protocol’s own sample-size justification is not reported in the registry record. Any illustration should therefore be treated as hypothetical rather than as evidence about the trial’s actual design or performance.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability in count outcomes exceeds what a model assumes. If a model does not account for that extra variability, its uncertainty estimates can be too narrow and its inferential conclusions too confident. This concept is most relevant to count data modeled across observations; it is not a reason to infer additional uncertainty for a binary response endpoint without knowing the analysis method and data.

The primary outcome is described as a participant count of responses, but the registry record does not report a fitted model, dispersion estimate, or inferential analysis. It would therefore be inappropriate to claim that over-dispersion was assessed or to assert that it affected the study result.

What is not documented?

The registry record does not report the primary endpoint’s observed result, the number assessed, an uncertainty interval, the statistical test or estimation method, or an analysis population definition. It also does not report interim analyses or the detailed statistical analysis plan. These omissions limit the ability to reproduce or evaluate the primary analysis. They do not establish that these methods or procedures were absent from the full study documentation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the objective response count, and lists no analyses. That record does not describe a plan for controlling multiplicity across outcomes, timepoints, subgroups, or statistical tests. A single listed primary outcome does not by itself establish that no additional analyses were conducted. A multiplicity strategy is not reported in the registry record.

The registry record also does not describe how missing response assessments were handled, how participants with no evaluable assessment were classified, or whether any sensitivity analyses were planned. The analysis population for the primary endpoint is not specified. These details matter because the response count and any rate depend on which participants are included and how absent assessments are treated.

The enrollment is recorded as 40, while the brief summary refers to up to 37 eligible subjects receiving the study drug. The registry record does not explain how those figures relate to the primary endpoint population. It would therefore be inappropriate to assume that all enrolled participants were eligible, treated, evaluable, or included in the response analysis.

No inferential analyses are listed. The record does not state whether any analysis was adjusted, whether interim analyses occurred, or whether the primary endpoint analysis followed a prespecified statistical plan. These items are not reported in the registry record; their absence from the registry entry should not be treated as proof that they did not occur.

11. 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

Serious events with the highest arm-level rate: treatment-related seconard maligancy (2.5%), sepsis (2.5%), respiratory failure (2.5%), pleural effusion (2.5%), thromboembolic event (2.5%).

The safety record lists the Etirinotecan Pegol group with 40 participants at risk for serious events and 5 affected. For other events, it lists 40 at risk and 0 affected. It also records 37 deaths. These are counts as entered in the registry record; they should not be converted into percentages without a stated analysis and appropriate interpretation.

The listed serious-event terms are “Treatment-related seconard maligancy,” “Sepsis,” “Respiratory Failure,” “Pleural Effusion,” and “Thromboembolic Event,” each reported as 2.5%. The record’s wording for the first term is retained as listed. These term-level entries do not supply event timing, duration, severity breakdown, or participant-level overlap. The percentages should not be summed or treated as a count of distinct participants.

The record does not specify the cause or timing of the 37 deaths, whether deaths were treatment-related, or how follow-up for these events was defined. It also does not provide detailed rules for adverse-event coding or collection. The listed counts describe the registry’s safety entries, not a comparison with an untreated or randomized control group. They should be read separately from the primary objective-response outcome, which is not reported.

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

The study’s stated purpose was to estimate objective response to etirinotecan pegol in patients with metastatic or recurrent NSCLC after failure of second-line therapy. The registry provides the endpoint definition—complete or partial response measured by RECIST version 1.1—and a timeframe of 6 weeks. It also identifies a single-group, open-label Phase 2 design.

The registry record does not report the observed response count, response rate, analysis denominator, or uncertainty interval. As a result, it does not establish the magnitude or precision of the primary efficacy outcome. The outcome definition alone cannot show how many participants responded, and enrollment cannot be used as a substitute for an endpoint analysis population.

Even a reported response result from this design would describe outcomes in the treated study group rather than establish a randomized comparison. Without a control arm, the study cannot separate the observed response from other explanations through an internal treatment contrast. The record also does not provide additional analysis details that would clarify adjustment, missing assessments, or the handling of participants who were not evaluable.

The safety entries record 5 participants affected by serious events, 0 affected by other events, and 37 deaths. The record does not provide enough detail to interpret the timing or cause of deaths, and the listed serious-event terms do not by themselves establish causation. These data do not fill the gap in the primary response result.

Accordingly, the registry record supports a description of the question, treatment, and design, along with limited safety counts. It does not support a numerical conclusion about the study’s objective response outcome or its statistical precision. Nor does it establish whether the response estimate differed from an alternative treatment or what caused the safety outcomes.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported result are both necessary for statistical interpretation. The registry specifies objective response as complete or partial response under RECIST version 1.1 and gives a timeframe of 6 weeks. But it does not report the response count, analysis denominator, or uncertainty. Without those pieces, readers can understand what the trial intended to measure but cannot evaluate the observed primary outcome.

It also demonstrates the distinction between estimating outcomes and comparing treatments. A single-group study can describe outcomes among treated participants, but it has no randomized control arm for a direct within-study comparison. The design information is therefore essential context for any interpretation, especially when the primary question concerns treatment in a defined setting.

The record’s enrollment and eligibility statements also show why analysis populations need to be explicit. Enrollment is recorded as 40, while the brief summary refers to up to 37 eligible subjects receiving the drug. Without a reported primary endpoint denominator and participant flow, those numbers do not identify who contributed to the response estimate.

Finally, safety counts and efficacy outcomes answer different questions. Serious-event counts, other-event counts, and deaths are recorded, but they cannot stand in for an unreported response result or determine treatment attribution. Clear reporting of outcome definitions, analysis populations, estimates, precision, and event context is central to allowing clinical researchers to assess what a trial’s results do and do not establish.

14. 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 direct limitation of the registry entry is that it does not report the observed primary response result. The response count, response rate, analysis denominator, and uncertainty interval are absent. Consequently, the main efficacy objective cannot be evaluated quantitatively from this record.

The study is single-group and open-label, with no randomized comparator. This limits interpretation to outcomes observed in the treated group and does not provide an internal control for a treatment comparison. The record does not describe masking of outcome assessment or independent review.

The enrollment of 40 and the brief summary’s reference to up to 37 eligible subjects are not reconciled. The registry record does not report participant flow, the number treated, the number assessed at 6 weeks, or the primary endpoint analysis population. It also does not explain missing or unevaluable outcome handling.

The registry lists serious-event counts, other-event counts, listed serious-event terms, and deaths, but does not report event timing, participant-level overlap, or the cause and treatment relationship of deaths. These gaps constrain interpretation of the safety entries.

The statistical analysis plan, sample-size justification, interim analyses, multiplicity procedures, and inferential methods are not reported in the registry record. The planning assumptions associated with the statistical material do not replace a trial-specific design justification, and their two-arm assumption differs from the recorded single-group trial design. These limitations concern what the registry documents; they do not prove that additional information is absent from other study records.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Etirinotecan Pegol (NKTR-102) in NSCLC — NCT01773109.
• Registry record last updated 2020-04-03; status last verified 2020-04.
• Results first posted 2020-04-03.
• 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.

18. Record Summary

The registry record describes a completed Phase 2, open-label, single-group study of etirinotecan pegol (NKTR-102) for metastatic or recurrent NSCLC after failure of second-line treatment. Enrollment is listed as 40. The brief summary says up to 37 eligible subjects would receive treatment every 3 weeks, and the arm description specifies 145 mg/m2 intravenously every 3 weeks.

The primary outcome is a participant count for complete or partial response by RECIST version 1.1, with a timeframe of 6 weeks. The observed response result and its statistical precision are not reported in the registry record. The safety entry lists 5 participants with serious events, 0 with other events, and 37 deaths; the record does not describe the timing or cause of those deaths.

The study is marked completed, with start recorded as 2013-01 and primary completion as 2016-01. Abramson Cancer Center at Penn Medicine is listed as sponsor. The statistical analysis plan and trial-specific sample-size justification are not reported in the registry record.