Study of IMC-11F8 in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of IMC-11F8 in Participants With Advanced Solid Tumors (NCT01088464), a non-randomized phase 1 study. The primary outcome is Number of Participants With 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs).

2. Clinical Question

This is a safety-focused early-phase question, not a test of whether IMC-11F8 is more effective than another treatment. The primary endpoint counts participants with at least one qualifying adverse event; it does not measure the number of events per participant, their duration, or their clinical importance. The registry definition includes events regardless of whether they were considered caused by study drug. It also defines treatment-emergent status by timing after the first dose, within the period after the last dose, or worsening during treatment for an event that began earlier.

The record also lists treatment-emergent anti-IMC-11F8 antibodies as a secondary outcome. A complete account of pharmacokinetic findings is not reported in the registry record. The central interpretive question is therefore limited to what the safety counts describe, how they are bounded by cohort sizes and observation rules, and what cannot be concluded without a control group or reported inferential analyses.

3. Trial Design

The registry identifies this as a Phase 1 study of IMC-11F8 in participants with advanced solid tumors. Its brief summary describes Japanese participants who had not responded to standard therapy or for whom standard therapy was unavailable. The stated aims were to establish the safety and pharmacokinetic profile of study drug administered on either a 3-week cycle or a 2-week cycle.

The design is listed as nonrandomized, unmasked, and single-group. The record contains three cohorts, all identified in the adverse-event grouping as Necitumumab cohorts. It does not provide cohort-specific descriptions, so the relationship between cohort membership and the two administration schedules is not reported in the registry record. The interventions are all named IMC-11F8, but the cohort treatment details, doses, and rules for entering or moving between cohorts are not reported in the registry record.

Enrollment is reported as 15. The study is listed as completed, with a start date of 2010-01 and primary completion in 2012-02. Those registry dates describe the study record and do not establish the duration of follow-up for each participant. The primary endpoint timeframe is stated separately as baseline up to 24 weeks plus 30 days after the last dose.

Because allocation was not randomized and there is no control arm, differences among the cohorts cannot be treated as randomized treatment effects. Cohort membership could reflect factors that are not described in the registry record. The record reports 15 outcome measures and no analyses. A sample-size justification, planned analysis approach, and detailed pharmacokinetic methods are not reported in the registry record. These omissions limit reconstruction of the intended comparisons and the context for interpreting the posted counts.

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: The study had 3 cohorts and dose escalation in successive cohorts was to occur once all the participants completed 1 cycle of therapy. A completed participant was either a participant who completed the initial 6-week treatment period (Cycle 1) or a participant who discontinued therapy for an IMC-11F8 (Necitumumab) related toxicity during Cycle 1.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received any quantity of study drug.

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: All enrolled participants who received any quantity of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs), measured over Baseline up to 24 weeks plus 30 days post last dose of study drug.

The primary endpoint is the number of participants with one or more treatment-emergent adverse events or serious adverse events. It is a participant-level count: a participant qualifies if at least one event meets the endpoint definition. It does not count every event separately, and the same participant is not counted again for each additional event under this measure.

The registry defines the safety population as all participants who received any quantity of study drug. An event is considered treatment-emergent if it occurs after the first dose, occurs up to 30 days after the last dose, or began before the first dose and worsens during treatment. The endpoint timeframe is baseline up to 24 weeks plus 30 days post last dose. Events are included regardless of causality, so the endpoint is not restricted to events judged to have been caused by the study drug.

In general, a participant-level adverse-event endpoint is useful in safety monitoring because it describes how many participants experienced at least one event under a specified definition and observation window. It gives a broad summary, but it does not convey event frequency, duration, severity distribution, or attribution on its own. The registry record does not report the combined primary endpoint value by cohort. Instead, the posted adverse-event figures distinguish serious events from other events, so those separate counts should not be mistaken for the combined primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is being counted?

The primary outcome is a count of participants who experienced one or more treatment-emergent adverse events or serious adverse events. In statistical terms, this is a binary status for each participant: the person either meets the endpoint definition or does not. The registry presents the result as a number of participants, rather than as a continuous measurement or a rate of events over time.

This distinction matters. A participant who experiences multiple qualifying events still contributes to the participant-level count as a participant with an event. The measure does not, by itself, describe how many total events occurred. Nor does it distinguish a single event from repeated events in the same person. The registry's separate serious and other adverse-event counts provide some descriptive separation by seriousness, but they do not replace the combined primary endpoint definition.

How is treatment-emergent status defined?

The registry's definition uses timing in relation to study treatment. An event qualifies if it occurs after the first dose or during the stated period after the last dose. An event that started before the first dose can also qualify if it worsened while the participant was on treatment. Events are counted regardless of causality. This means the endpoint records temporal occurrence under the stated rules; it does not assert that the study drug caused every included event.

The primary endpoint timeframe is baseline up to 24 weeks plus 30 days post last dose of study drug. In general, a defined observation window helps make safety summaries interpretable because it specifies which events are eligible for inclusion. A window also sets limits: events outside it are not represented by this endpoint, and differences in participants' time under observation can affect the chance of recording an event. Participant-level follow-up details and handling of incomplete observation are not reported in the registry record.

What do the cohort counts represent?

The adverse-event record gives, for each cohort, the number at risk and the number affected for serious events and for other events. These are descriptive counts. For example, Cohort 1 reports 1 serious-event participant among 3 at risk; Cohort 2 reports 0 among 6; and Cohort 3 reports 1 among 6. The other-event counts are 3 among 3, 6 among 6, and 6 among 6. Keeping each cohort separate avoids creating an unreported pooled result.

In general, a proportion can be formed by relating an event count to the number at risk, but a calculation from these counts would be a simple descriptive re-calculation, not an adjusted estimate or a randomized comparison. It would not resolve uncertainty about who experienced both serious and other events, nor would it supply a causal interpretation. The registry record does not report confidence intervals, hypothesis tests, or adjusted estimates for these safety outcomes.

Why does the design matter?

Random allocation can help balance known and unknown participant characteristics across treatment groups. This study is listed as nonrandomized and single-group, with three cohorts but no like-for-like control comparison. Cohort-to-cohort differences may reflect different participant characteristics, follow-up, schedules, or other factors not described in the record. In general, those differences cannot be isolated as treatment effects without a suitable design and analysis.

The record mentions administration in a 3-week cycle or a 2-week cycle, but the cohort descriptions are blank. The mapping from these schedules to individual cohorts is therefore not reported in the registry record. The study is unmasked, so neither participants nor study personnel are described as blinded. No further details of event ascertainment or independent review are reported in the registry record.

What can an interval or test add?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. Its width reflects precision: wider intervals indicate greater uncertainty, while narrower intervals indicate more precision under the method's assumptions. A hypothesis test addresses whether the data are sufficiently inconsistent with a specified null hypothesis. Neither device removes design limitations, and neither turns an observational cohort contrast into a randomized effect.

No confidence intervals, p-values, or inferential analyses are reported in the registry record. As a result, the posted counts should be read as observed descriptive summaries rather than as precise estimates of underlying event probabilities or evidence from a significance test. The record does not report the statistical analysis plan, any model choice, or any approach to handling multiplicity.

How should planning calculations be understood?

In general, a sample-size calculation is a planning exercise that asks how much information a proposed design might need under stated assumptions. It is not a measure of the evidential strength of an already completed study. Any planning illustration based on an observed effect is hypothetical and should not be described as observed power. The registry record does not report a sample-size justification for this trial, and the nonrandomized, single-group design does not provide the like-for-like treatment contrast required for a conventional two-arm comparison to answer a causal question.

Overall, the main statistical contribution of the posted safety data is descriptive: they record participant counts under defined event categories and a defined observation period. The record lacks the analysis details needed to move from those counts to adjusted estimates, formal uncertainty intervals, or causal comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and identifies treatment-emergent anti-IMC-11F8 antibodies as a secondary outcome. It reports no analyses. The registry record does not report whether outcomes were organized into a prespecified hierarchy, whether selected outcomes were prioritized for formal testing, or whether any adjustment for multiple testing was planned. The existence of multiple outcome measures does not by itself establish that multiple hypothesis tests were performed.

In general, multiplicity arises when several statistical hypotheses are tested: the chance of at least one false-positive result can increase as the number of tests increases. Methods such as a prespecified testing hierarchy or an adjustment to the significance threshold can address that issue, but the appropriate approach depends on the objectives and analysis plan. No such approach is reported in the registry record, and there are no reported inferential analyses to interpret.

The primary safety population is defined as all participants who received any quantity of study drug. The registry does not report the number included in that population or how participants with incomplete follow-up were handled. It also does not report missing-data rules for adverse-event status, pharmacokinetic measures, or the antibody outcome. In general, missingness can affect interpretation when participants with unavailable measurements differ from those with recorded measurements.

The cohort descriptions and analysis populations are not specified beyond the primary safety population definition. There is no reported approach for protocol deviations, partial observations, or participants who discontinued treatment. These omissions prevent assessment of whether the posted counts represent complete follow-up under the endpoint window or how unavailable data were treated.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: dyspnoea (33.3%), oropharyngeal discomfort (33.3%), hepatic function abnormal (16.7%).

The serious adverse-event counts are reported separately for each cohort: Cohort 1 had 1 participant affected among 3 at risk, Cohort 2 had 0 among 6, and Cohort 3 had 1 among 6. The corresponding counts for other adverse events are 3 among 3, 6 among 6, and 6 among 6. These figures count participants affected, not the total number of individual events.

The registry also lists Dyspnoea and Oropharyngeal discomfort at 33.3% each, and Hepatic function abnormal at 16.7%, among the top serious-event terms. The denominators for these term percentages are not reported in the registry record. Death counts are also not reported in the registry record.

In general, a serious adverse event is a seriousness classification, not a judgment that the event was caused by treatment. The primary endpoint includes events regardless of causality, and the posted serious-event counts should be read in that descriptive context. The figures do not show whether the same participants experienced serious and other events, and they do not give event timing, severity grades, or duration. They should not be summed or interpreted as a combined primary endpoint value.

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

The posted results describe adverse events recorded in three nonrandomized cohorts during the study's defined safety observation period. They show the number of participants reported with serious events and with other events in each cohort, along with selected serious-event terms. The counts are descriptive observations from this study, not comparative estimates against a control group.

They do not establish that IMC-11F8 caused an event, because the record says events were included regardless of causality. Nor do they establish that the study drug prevents events or improves outcomes. There is no randomized control group, and the registry does not report inferential analyses. The record also does not provide a combined value for the primary endpoint of participants with one or more treatment-emergent adverse events or serious adverse events.

In general, the absence of a reported event in a cohort count is not proof that an event cannot occur. Counts from groups with limited numbers of participants have considerable uncertainty, and no confidence intervals are reported in the registry record. The event-term percentages likewise lack accompanying denominators in the record, limiting their interpretation as measures of frequency.

The study summary states that safety and pharmacokinetic profiling were aims, and the registry lists an antibody outcome. The posted safety counts alone do not answer the pharmacokinetic question or provide a complete account of immunogenicity. Detailed pharmacokinetic results and analysis methods are not reported in the registry record. The record therefore supports a narrow reading of observed safety counts, not a broad conclusion about comparative safety, efficacy, or the probability of future outcomes.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a safety description and a comparative treatment estimate. A single-group, nonrandomized study can record events during treatment and describe who experienced them, but it lacks a randomized control group for separating treatment effects from other explanations. That distinction remains important even when adverse-event counts are presented by cohort.

The endpoint definition also demonstrates why statistical summaries need to be read precisely. A count of participants with one or more events differs from a count of all events. It combines participants with different event histories into a single status and depends on the definition of treatment-emergent timing. The record's rule includes events regardless of causality, so the endpoint answers a descriptive safety question rather than a causal attribution question.

The cohort data further show why denominators and missing context matter. Counts should be interpreted within their cohort and event category, not pooled informally. The record does not identify which cohort followed which administration schedule, and the cohort descriptions are blank. It also does not report confidence intervals or inferential analyses. A numerical difference between groups, if one is noticed, would not on its own show that schedules or treatments differ.

Finally, the record labels the study intervention as IMC-11F8 while its adverse-event group titles use Necitumumab. Without an explanation of that labeling in the registry record, readers should avoid assuming how those labels relate. These features make the record a useful example of how design, outcome definitions, denominators, and reporting completeness govern what safety statistics can support.

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 registry record leaves several trial-specific details unavailable. Although the brief summary mentions administration in a 3-week cycle or a 2-week cycle, cohort descriptions are blank, so the schedule assigned to each cohort is not reported in the registry record. Doses, dose-escalation rules, and other cohort procedures are not reported in the registry record either.

The intervention is named IMC-11F8, while adverse-event group titles identify Cohort 1, Cohort 2, and Cohort 3 as Necitumumab cohorts. The registry record does not explain this difference in labeling. The listed primary endpoint is a combined count of participants with one or more treatment-emergent adverse events or serious adverse events, but the posted adverse-event figures separate serious events from other events. The combined endpoint count is not reported in the registry record.

The record does not provide participant-level event histories, overlap between serious and other events, event severity grades, timing, duration, or causality assessments for the posted counts. Denominators for the listed serious-event term percentages are not reported in the registry record. Death counts are not reported in the registry record.

The registry reports no analyses. A statistical analysis plan, confidence intervals, missing-data methods, multiplicity approach, sample-size justification, and detailed analysis populations beyond the primary safety population definition are not reported in the registry record. These limitations prevent reconstruction of inferential results or a detailed assessment of uncertainty. The nonrandomized, unmasked, single-group design also limits causal and between-cohort interpretations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of IMC-11F8 in Participants With Advanced Solid Tumors — NCT01088464.
• Registry record last updated 2017-02-03; status last verified 2016-12.
• Results first posted 2017-02-03.
• 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 1, nonrandomized, unmasked, single-group study of IMC-11F8 in Japanese participants with advanced solid tumors. Enrollment is reported as 15. The study summary states that the drug was administered in either a 3-week cycle or a 2-week cycle. Cohort-specific schedules are not reported in the registry record.

The primary endpoint is the number of participants with one or more treatment-emergent adverse events or serious adverse events, regardless of causality, over the stated timeframe. Posted adverse-event counts are separated by cohort and by serious versus other events. The record lists treatment-emergent anti-IMC-11F8 antibodies as a secondary outcome, reports 15 outcome measures, and reports no analyses.

Because there is no randomized control group and no inferential analysis, the posted safety figures should be interpreted as descriptive counts. The record does not report a combined primary endpoint value, confidence intervals, or a statistical analysis plan.