Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma (NCT02034123), a non-randomized phase 1 study. The primary outcome is Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs.

2. Clinical Question

3. Trial Design

This was a phase I, open-label, non-randomized, two-part study of oral GSK2879552 in participants with relapsed or refractory small cell lung carcinoma. The registry lists a single-group model and an enrollment of 29. Because there was no randomized control group, the listed dose groups should not be interpreted as treatment-versus-control comparisons.

Part 1 was a dose-escalation phase intended to identify a recommended phase 2 dose, using safety, tolerability, pharmacokinetic and pharmacodynamic information. The registry says dose escalation was guided by the Neuenschwander continuous reassessment method (N-CRM), with safety constraints intended to limit exposure to undue toxicity. It also says dose levels could be expanded up to 12 subjects for additional pharmacokinetic and pharmacodynamic data.

Part 2 was planned as an expansion cohort after the recommended dose was identified, with up to 30 subjects intended to further evaluate clinical activity and tolerability. The posted adverse-event groups list participants at risk in Part 1, while the listed Part 2 groups have zero participants at risk. The registry status is terminated; the reason for termination is not reported in the registry record.

The study started on 2014-02-04, and the primary completion date is 2017-04-18. These design details describe the study structure, but they do not establish how many participants were assessed at each planned stage or why enrollment and follow-up ended as recorded.

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: This study was terminated early during Part 1 as the risk benefit in relapsed refractory SCLC did not favor continuation of the study. Data was collected only in Part 1 and no participants were enrolled in Part 2. A total of 29 participants enrolled and received treatment in Part 1. Of which 7 prematurely withdrawn and 22 completed study.

Only the first 6 of 18 groups are shown.

Part1(Median of 7.286 Weeks of Exposure)

Reasons for not completing this period:

Part2(Up to 2 Years)

Analysis population for the primary outcome, as defined in the registry: All Treated Population

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.

Population: Data was collected only in Part 1 and no participants were enrolled in Part 2.

Only the first 6 of 19 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs, measured over Median of 7.286 weeks of drug exposure.

The primary endpoint counts participants with serious adverse events and non-serious adverse events in Part 1. An adverse event is defined in the registry as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. An SAE is an event meeting the registry's seriousness criteria, which include death, life-threatening occurrence, hospitalization or prolongation of hospitalization, disability, congenital anomaly or birth defect, and specified other situations associated with liver injury or impaired liver function.

Counting participants with events is a direct descriptive way to report safety experience during early dose escalation. Such counts can help characterize the types and frequency of observed events within the treated groups, while retaining the distinction between serious and non-serious events. The registry defines the analysis population as participants who received at least one dose of study treatment. Its stated timeframe is a median of 7.286 weeks of drug exposure.

These counts do not, by themselves, establish that an event was caused by treatment. They also do not compare risks against a control group. The primary endpoint is restricted to Part 1; a primary endpoint result for Part 2 is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a participant count: the number of people with at least one event in the relevant category. It is not a measurement of event severity on a numerical scale, nor a time-to-event estimate. The registry separates serious from non-serious adverse events and gives the participants at risk and affected in each listed dose group. This lets readers see the observed counts in context of the group size without treating the groups as randomized comparisons.

What does an event count convey?

As a general statistical concept, a count describes what was observed in the analysis population during the specified observation period. A count alone does not express uncertainty as fully as an interval estimate would. With small groups, each additional participant with an event can visibly change the count and any rate calculated from it. No interval estimates for this endpoint are reported in the registry record, so the posted counts should be read as descriptive observations rather than precise estimates of event risk.

The denominator matters. The primary analysis population is the All Treated Population, defined as participants who received at least one dose. The adverse-event listing separately reports the number at risk within each dose group. These quantities help clarify how many participants were included in a group's safety description, but the registry record does not provide further details about exposure time or follow-up for every individual. A median exposure duration is reported, but it cannot substitute for participant-level exposure information.

Why does the design affect interpretation?

As a general concept, random allocation helps balance measured and unmeasured characteristics between comparison groups on average. This study was explicitly non-randomized and single-group, with dose escalation rather than a control arm. The dose groups therefore do not constitute a randomized comparison. Dose assignment in an escalation study is connected to the sequence of safety and pharmacokinetic/pharmacodynamic review described in the record. A difference in event counts across dose groups cannot be attributed to dose alone based on these counts.

The registry says the escalation was guided by the Neuenschwander continuous reassessment method (N-CRM), with safety constraints. In general, a continuous reassessment approach uses accumulating information about dose and toxicity to guide dose decisions. The registry's description does not report the specific model details, toxicity target, decision rules, or operational implementation; those details are not reported in the registry record. The description should not be expanded into claims about the exact analysis conducted.

How should SAE categories be read?

The registry defines an SAE through seriousness criteria, not through proof that the study drug caused the event. The definition includes specified outcomes and circumstances, while the adverse-event definition itself applies whether or not a relationship to the medicinal product is considered. Thus, the SAE count answers how many participants met the event category in the safety reporting, rather than how many events were confirmed to be caused by treatment. Attribution details beyond the endpoint description are not reported in the registry record.

Term-specific percentages are also descriptive. The record gives percentages for selected serious-event terms, but it does not provide enough information in the registry record to define every denominator or explain whether participants could contribute to multiple terms. These percentages should not be converted into comparisons between doses or treated as causal estimates.

What can planning calculations tell readers?

General sample-size calculations based on an observed effect are planning illustrations, not evidence that a trial had a particular probability of detecting an effect. The stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect framed as a fraction of an observed effect. Such illustrations are not the design justification for this study: the study was non-randomized and single-group, and its stated objective was dose escalation. A sample-size justification for the actual trial is not reported in the registry record.

For binary outcomes, statistical precision depends on the number of participants and observed events. In general, sparse event counts yield substantial uncertainty, especially when groups are small. Since this endpoint has counts rather than a randomized contrast, conventional treatment-effect interpretation is not appropriate. The registry lists zero analyses, and no inferential analysis of this primary safety endpoint is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 40 outcome measures, including the primary safety endpoint and pharmacokinetic outcomes. The study also had a dose-escalation objective and a planned expansion objective, which address different questions. A prespecified statistical plan describing how multiple outcomes or dose groups were handled is not reported in the registry record. No multiplicity adjustment or hierarchy for interpreting outcomes is reported either.

Multiplicity matters in general when many outcomes, groups, or analyses are examined: the chance of finding an apparently unusual result can increase as the number of comparisons grows. That general concern does not establish that any particular result is spurious. In this record, the primary outcome is presented descriptively, and the registry lists zero analyses. No adjusted or unadjusted inferential comparisons for the primary endpoint are reported in the registry record.

The primary population is the All Treated Population, defined as participants who received at least one dose. The registry does not report, in the registry record for this endpoint, the number excluded from that population, a participant flow accounting for missing safety data, or the handling of missing event information. Missing-data methods and the extent of missing outcome data are not reported in the registry record. The stated median of 7.286 weeks of drug exposure does not describe the completeness of follow-up for each participant.

These omissions limit assessment of how complete the endpoint data were and how the outcomes were selected or interpreted. They do not imply that data were missing or that multiplicity altered the results; those details are simply not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (50.0%), myocardial infarction (50.0%), tumour lysis syndrome (50.0%), encephalopathy (33.3%), malaise (33.3%).

The serious adverse-event figures are participant counts within dose groups. For each group, the registry identifies participants at risk and participants affected; the non-serious adverse-event counts are listed separately. Read each count alongside its own group size and schedule. The groups are small and unequal, so the counts are descriptive and should not be treated as stable estimates of the chance of an event.

The listed Part 1 groups include participants affected by SAEs at some dose levels; other Part 1 dose groups list no SAE-affected participants. The record also lists deaths in the 2.0 mg Daily group and the 4.0 mg 4 Days on/10 Days Off group. These entries describe the posted safety counts; the endpoint details do not establish that a listed event or death was caused by GSK2879552. The specific causal relationship is not reported in the registry record.

Selected serious-event terms include atrial fibrillation, myocardial infarction, tumour lysis syndrome, encephalopathy, malaise and tumour pain. The percentages attached to these terms are descriptive listings and should not be interpreted as comparative risks. The listed Part 2 groups have zero participants at risk, so they do not provide safety experience for the planned expansion cohort.

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

The registry record describes a phase I investigation of GSK2879552 in relapsed or refractory small cell lung carcinoma, with dose escalation as its first part and an intended expansion after a recommended phase 2 dose was identified. The primary outcome is a count of participants with SAEs and non-SAEs in Part 1. The posted figures therefore document adverse events observed in the treated dose groups during the reported exposure period.

Those figures do not establish that GSK2879552 caused any particular event. An adverse event is defined by its temporal association with use of a medicinal product, whether or not it is considered related. The registry's safety counts are not a randomized comparison, and there is no control group against which to estimate a relative treatment effect. Differences among dose groups should not be treated as causal dose effects.

The record also does not establish clinical benefit. Although the planned expansion was intended to evaluate clinical activity and tolerability, the listed Part 2 groups have zero participants at risk. The primary endpoint is a safety outcome, and no clinical-activity result is included in the primary outcome details. A conclusion about effectiveness, or about whether the treatment is preferable to another option, cannot be drawn from these data.

The limited and uneven group sizes and the median exposure of 7.286 weeks constrain precision and context. The record does not report confidence intervals for the primary counts, participant-level follow-up, detailed missing-data handling, or the reason for termination. These limits leave uncertainty about the breadth and completeness of the available safety experience; they do not change what the posted counts themselves record.

13. Why This Trial Matters Statistically

This study illustrates why design details are essential when reading clinical trial statistics. A phase I dose-escalation study has a different purpose from a randomized comparative trial. Here, the stated focus was to identify a recommended phase 2 dose using safety, tolerability, pharmacokinetic and pharmacodynamic information. The listed event counts belong to dose groups formed within that escalation design, not to randomized arms intended to estimate a treatment contrast.

The record also makes the analysis population explicit: participants who received at least one dose. That definition matters because safety summaries concern exposure to study treatment, while enrollment alone does not mean that every participant received treatment or contributed to every outcome. The registry's median drug-exposure duration adds context, but it cannot describe each participant's observation period.

Another statistical lesson is that event counts in small groups are informative as observations but limited as precise risk estimates. Reporting the number at risk beside the number affected is important, especially where group sizes vary. Term-specific percentages and counts also require careful interpretation: they describe reported events and do not establish attribution or provide a controlled comparison.

Finally, a planned expansion does not itself demonstrate that expansion data were collected. The posted Part 2 groups list zero participants at risk, while the study is marked terminated. This distinction helps separate the intended study design from the available safety record. Together, these features show how trial structure, population definitions, exposure, and the completeness of reported outcomes govern what can be inferred from clinical safety statistics.

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 study is non-randomized and single-group, so the dose groups are not equivalent control groups. Their observed safety counts cannot isolate a causal effect of dose or treatment. Dose assignment occurred in an escalation framework described as guided by N-CRM and safety constraints, but the detailed operating rules and dose-decision record are not reported in the registry record.

The groups are small and have different numbers at risk. The median drug exposure is 7.286 weeks, but individual exposure and follow-up details are not reported in the registry record. Confidence intervals for the primary safety counts are also not reported, leaving the precision of the group-specific observations unclear.

The primary endpoint is limited to Part 1. The planned Part 2 expansion was intended to evaluate clinical activity and tolerability, but the listed Part 2 groups have zero participants at risk. The reason for termination is not reported in the registry record. The registry lists 40 outcome measures, but the analysis plan, multiplicity strategy, and detailed missing-data methods are not reported. The record also does not establish whether every event was treatment-related or provide a comparative control outcome. These limitations restrict interpretation to a descriptive account of the posted Part 1 safety experience.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma — NCT02034123.
• Registry record last updated 2019-12-06; status last verified 2019-11.
• Results first posted 2019-01-23.
• 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

NCT02034123 is a phase I, open-label, non-randomized, single-group study of oral GSK2879552 in relapsed or refractory small cell lung carcinoma. The registry lists 29 participants enrolled and a two-part design: Part 1 dose escalation and a planned Part 2 expansion. The primary outcome counts participants with serious and non-serious adverse events in the All Treated Population, defined as participants who received at least one dose. The reported median drug exposure is 7.286 weeks.

The posted adverse-event groups contain Part 1 safety counts; the listed Part 2 groups have zero participants at risk. The study status is terminated, and the reason is not reported in the registry record. No randomized control comparison is available, and the primary endpoint does not measure clinical benefit.