Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma (NCT02363283), a na phase 2 study. The primary outcome is Overall Response Rate Using Response Evaluation Criteria in Solid Tumors Version 1.1.

2. Clinical Question

3. Trial Design

This completed phase II study evaluated glembatumumab vedotin in patients with metastatic or locally recurrent uveal melanoma. The registry lists 37 participants enrolled. The recorded start date is 2015-09-16, and the primary completion date is 2018-07-02. The sponsor was the National Cancer Institute (NCI).

The design is recorded as single-group, with allocation listed as NA and masking as none. Participants in the treatment group received glembatumumab vedotin intravenously over 90 minutes every 3 weeks, unless disease progression or unacceptable toxicity occurred. Laboratory biomarker analysis and a pharmacological study were also listed. Because no control group is described, the study is not a randomized comparison and cannot directly estimate a treatment contrast against a concurrent comparator.

The primary outcome was overall response rate using RECIST v1.1. Its stated assessment window extended from the date of treatment until the first documented progression or death from any cause, assessed up to 2 years and 10 months. The registry also lists secondary outcomes involving change in glycoprotein NMB expression on tumor tissue, progression-free survival, grade 3-4 adverse events according to National Cancer Institute Common Toxicity Criteria Version 4.0, and overall survival.

The registry record does not report the detailed protocol, eligibility criteria, treatment dose, sample-size justification, or a full statistical analysis plan. It also does not report primary endpoint results. The enrollment figure describes the study enrollment, whereas the primary endpoint population is specifically described as participants who entered the study and received treatment. These descriptions should not be treated as proof that every enrolled participant contributed to the primary analysis.

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: 2 participants withdrew consents prior to starting therapy and 1 failed eligibility criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: participants who entered study and received treatment

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 Response Rate Using Response Evaluation Criteria in Solid Tumors Version 1.1, measured over From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years and 10 months.

Overall response rate is a binary participant-level outcome: each participant is classified according to whether the tumor response meets the endpoint criteria. The registry describes the primary endpoint as a count of participants, rather than reporting a rate or a model-based estimate. The criteria are based on RECIST v1.1 and imaging by MRI and/or CT. A partial response requires a 30% or greater decrease in the sum of the longest diameter of target lesions. A complete response is the disappearance of all target lesions. Stable disease meets neither the criteria for partial response nor those for progressive disease. Progressive disease includes a 20% increase in the sum of target-lesion diameters, a measurable increase in a non-target lesion, or new lesions.

Response endpoints provide a structured way to describe tumor change using prespecified categories. They are distinct from time-to-event outcomes such as progression-free survival or overall survival: response classification records whether specified imaging criteria were met, while time-to-event outcomes concern how long it takes for a defined event to occur. The registry states that the primary outcome was assessed from treatment until progression or death, up to 2 years and 10 months.

The primary endpoint’s result is not reported in the registry record. There is no response count or overall response rate to interpret, and no confidence interval or endpoint-specific analysis is reported. The definition explains what would count as a response; it does not establish how many participants met that definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a participant-level binary outcome: a participant either meets the specified response classification or does not. The registry describes the endpoint as a count of participants and identifies RECIST v1.1 as the response framework. That definition is useful for understanding what the study intended to measure, but it is not itself an analysis result. The registry record does not report how many participants had a response, the overall response rate, or an interval estimate.

What does a confidence interval describe?

General statistical explanation: a confidence interval expresses the uncertainty around an estimate under the assumptions of the analysis. For a response proportion, an interval would indicate how imprecisely the underlying response frequency is estimated from the observed participants. An interval is not a guarantee that the true value lies within its limits, and it does not correct problems such as selection bias, missing outcome assessments, or lack of a control group. No confidence interval for the primary endpoint is reported in the registry record.

What can a single-group design estimate?

General statistical explanation: a single-group study can describe outcomes observed among participants receiving the study treatment. It cannot, on its own, separate the treatment’s contribution from other explanations for those outcomes, such as the natural course of illness, participant selection, or assessment processes. A randomized comparator can support a treatment contrast by balancing measured and unmeasured factors in expectation; this trial is not described as randomized and has no like-for-like control arm. Accordingly, a response summary, even if available, would not answer the same question as a randomized comparison.

How should the response criteria be understood?

RECIST v1.1 classifies tumor status using imaging-based measurements and categories. The registry describes complete response as disappearance of all target lesions, and partial response as a 30% or greater reduction in the sum of the longest diameter of target lesions. Stable disease is neither sufficient shrinkage for partial response nor sufficient increase for progression. Progression includes a 20% increase in target-lesion measurements, a measurable increase in a non-target lesion, or new lesions. These definitions make the endpoint more explicit than an informal judgment of improvement, but they do not remove measurement variability or provide a result when outcome data are absent.

Why do analysis populations matter?

General statistical explanation: the population included in an analysis affects what the estimate describes. An analysis of all randomized participants, all treated participants, or only participants with evaluable scans can answer different questions. This study is single-group, and the primary population is described as participants who entered the study and received treatment. The registry does not report the number included in the primary endpoint analysis, the number with evaluable imaging, or how participants without an endpoint assessment were handled. Enrollment of 37 should therefore not automatically be taken as the primary analysis denominator.

What does missing analysis detail leave uncertain?

The registry record does not report a full statistical analysis plan, the method used to calculate the primary endpoint, any adjustment or stratification, or the handling of missing observations. It also does not report interim analyses or a sample-size justification. General statistical explanation: prespecified methods help readers distinguish planned analyses from choices made after outcomes are known. Missingness can also affect a binary endpoint if participants without an assessment are excluded or classified in a particular way. Without the protocol or analysis details, those decisions cannot be evaluated from the registry record.

How should planning illustrations be read?

General statistical explanation: a sample-size calculation describes a hypothetical design under stated assumptions. It is not a result from the enrolled participants, and it is not observed power. The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These assumptions describe a planning exercise; they do not turn this single-group trial into a two-arm randomized comparison. Sample-size justification for the actual trial is not reported in the registry record.

For count outcomes, over-dispersion is a general concern when observed variability exceeds what a simple model assumes. It can make uncertainty estimates too narrow if not accounted for. The primary endpoint is a participant count, but the registry record does not identify a model or report a dispersion estimate. No claim about over-dispersion or its handling can therefore be made for this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes covering change in glycoprotein NMB expression, progression-free survival, grade 3-4 adverse events, and overall survival. It also records five outcome measures. Testing multiple endpoints can raise a general statistical issue: when many hypotheses are examined, the chance of at least one apparently notable finding can increase unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity adjustment, a testing hierarchy, or which secondary outcomes were intended to be confirmatory. It is therefore not possible to determine how multiplicity was handled.

Missing-data methods are also not reported. The primary population is described as participants who entered the study and received treatment, but the record does not state how many participants had an evaluable response assessment or how missing imaging was handled. It does not report whether participants without an assessment were excluded, classified in a particular response category, or addressed through another method. These choices can affect what a response estimate represents.

The record does not report the primary endpoint result or any outcome-specific analysis details. It lists no analyses. Detailed rules for censoring time-to-event outcomes, accounting for incomplete follow-up, or defining the analysis population for secondary outcomes are not reported in the registry record. Consequently, the outcomes and their definitions can be described, but their statistical results and the safeguards used to manage multiple testing or missing observations cannot be evaluated.

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

Serious events with the highest arm-level rate: alopecia (80.0%), leukopenia (68.6%), elevated alt/ast (62.9%), neutropenia (60.0%), fatigue (57.1%).

The treatment group’s serious-adverse-event summary lists 35 participants at risk and 34 affected. The other adverse-event summary lists 35 at risk and 0 affected, and 1 death is recorded. These are registry counts; they should not be converted into additional percentages or interpreted as a comparison between randomized arms. The study is recorded as single-group, so the other group does not constitute a like-for-like control comparison.

The registry also lists alopecia at 80.0%, leukopenia at 68.6%, elevated ALT/AST at 62.9%, neutropenia at 60.0%, fatigue at 57.1%, and maculopapular rash at 54.3% among the top serious terms. The registry record does not provide enough detail to determine the timing, duration, recurrence, or attribution of these events, or how the listed percentages relate to event counts for individual participants. The one recorded death is not characterized by cause in the record.

These summaries describe reported safety information, not the primary response endpoint. They do not establish that an event was caused by treatment, and they do not support a controlled comparison of safety between treatments.

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

The registry record establishes that a phase II, single-group study of glembatumumab vedotin was completed, with 37 participants enrolled. It defines the primary endpoint as an overall response count assessed under RECIST v1.1 and describes the treatment schedule and safety summaries. These details explain what the study was intended to evaluate and how its primary response categories were defined.

The record does not report the primary response count or overall response rate. It therefore does not show how many treated participants met the complete or partial response criteria, nor how precisely that outcome was estimated. The absence of an endpoint result is not evidence that responses did or did not occur. The listed secondary outcomes likewise should not be treated as results; their outcome-specific estimates are not reported in the registry record.

The single-group design also limits what any observed response result could establish. Without a concurrent control group, outcomes in the treated participants cannot be directly contrasted with outcomes under another treatment or a control condition. This design feature does not erase the descriptive value of a response count, but it limits causal interpretation.

The safety entries provide counts and listed event terms, but the record does not fully describe timing, attribution, or the context of the recorded death. The presented information should be read as registry-reported safety data rather than as proof of causation or a controlled safety comparison.

In short, the registry supports interpretation of the study’s design and measurement framework, but not a conclusion about the primary response outcome. The trial’s completed status does not supply the missing outcome estimate, and planning calculations are not substitutes for observed results.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between defining an endpoint and reporting its result. The registry specifies a primary outcome, the response framework, the assessment population, and an assessment window extending up to 2 years and 10 months. Those details make the intended measurement understandable. Yet the response count and rate are not reported in the registry record, so the central endpoint cannot be quantitatively assessed from the available registry results.

The design also illustrates why study structure governs interpretation. A single-group study can describe outcomes in participants who received treatment, but it cannot provide a randomized treatment contrast. The registry records allocation as NA and masking as none; there is no like-for-like control group. Even a fully reported response estimate would need to be interpreted as a within-group observation rather than a controlled estimate of treatment effect.

The record separates primary and secondary outcomes, including imaging response, survival outcomes, biomarker change, and adverse events. That range of outcome types underscores the need for clear analysis populations and prespecified methods. The registry does not report multiplicity handling, missing-data methods, an interim-analysis plan, or detailed statistical methods. These omissions constrain assessment of how results would have been estimated and how uncertainty would have been represented.

Finally, the safety summaries show why counts and event labels require context. The record gives numbers at risk and affected, selected event terms, and a death count, but limited detail about timing and attribution. Statistical interpretation depends not only on the values recorded but also on knowing who was analyzed, how outcomes were assessed, and how incomplete information was handled. Those details are not reported for several outcomes in this record.

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.

Several trial-specific limitations restrict interpretation of the registry record. The most direct is the absence of the primary outcome result: no response count, overall response rate, or confidence interval is reported. Although the endpoint definition and assessment window are described, they do not permit an estimate of the observed response frequency.

The single-group design has no like-for-like control arm. Allocation is recorded as NA and masking as none, so the study cannot support a randomized comparison. A descriptive outcome in treated participants would not by itself isolate a treatment effect from other influences. The registry’s enrollment of 37 also does not establish the denominator used for the primary analysis, which is described as participants who entered the study and received treatment.

The registry record does not report the number of participants with evaluable imaging, the handling of missing assessments, or detailed analysis populations for secondary outcomes. It also does not report a full statistical analysis plan, sample-size justification, multiplicity procedures, interim analyses, or censoring rules for time-to-event outcomes. These omissions limit evaluation of bias, precision, and reproducibility.

Safety information is reported through counts and selected terms, but event timing, attribution, and the context of the recorded death are not given. The available summaries therefore do not permit a detailed assessment of event patterns or a controlled safety comparison. These limitations concern what can be concluded from the registry record; they do not establish that unreported analyses were or were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma — NCT02363283.
• Registry record last updated 2020-08-21; status last verified 2020-07.
• Results first posted 2020-08-21.
• 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

NCT02363283 is a completed phase II, single-group study of glembatumumab vedotin for metastatic or locally recurrent uveal melanoma. The registry lists 37 participants enrolled, no masking, and no randomized allocation. Treatment was described as an intravenous infusion over 90 minutes every 3 weeks in the absence of progression or unacceptable toxicity.

The primary endpoint was an overall response count under RECIST v1.1, among participants who entered the study and received treatment. The registry record does not report the response count or overall response rate. Secondary outcomes included biomarker change, progression-free survival, grade 3-4 adverse events, and overall survival.

Safety summaries list 35 participants at risk and 34 affected for serious adverse events, 35 at risk and 0 affected for the other adverse-event group, and 1 death. The registry does not report detailed statistical methods, missing-data handling, or multiplicity procedures.