Study of Vimseltinib for Tenosynovial Giant Cell Tumor: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Vimseltinib for Tenosynovial Giant Cell Tumor (NCT05059262), a randomized phase 3 study. The primary outcome is Objective Response Rate (ORR) at Week 25 Per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

2. Clinical Question

This question is about a measured imaging response during the randomized, blinded comparison. It is not a direct test of every possible benefit or risk, and the primary outcome does not by itself describe changes in symptoms, physical function, or long-term tumor control. The registry lists those kinds of outcomes separately, including range of motion and patient-reported measures.

3. Trial Design

MOTION is a Phase 3, randomized, placebo-controlled, double-blind study of vimseltinib in TGCT. The registry describes quadruple masking and a crossover model. Its summary describes two parts: a 24-week blinded comparison of vimseltinib with matching placebo, followed by an open-label treatment phase in which participants receive vimseltinib. Participants assigned to placebo in Part 1 could receive vimseltinib in Part 2.

The registry lists enrollment as 123. The primary endpoint is assessed from baseline to Week 25, identified as Cycle 7, Day 1. The primary analysis population is the ITT Set, defined in the record as participants randomized to a study treatment regimen. For the primary outcome, tumors were assessed by blinded independent radiologic review using RECIST Version 1.1. The record identifies the sponsor’s comparison method as Cochran-Mantel-Haenszel.

The trial began on 2021-10-14, and the registry lists primary completion as 2023-08-10. Its status is active, not recruiting. These registry fields describe the trial record; they do not establish that every planned analysis or follow-up activity is complete. The protocol’s allocation details beyond randomization, including the sequence-generation process and any stratification factors, are not reported in the registry record.

The clinical comparison of interest is the blinded Part 1 contrast. Because the placebo group could switch to open-label vimseltinib in Part 2, later observations do not preserve a continuing randomized placebo comparison in the same way. The record describes Part 2 as long-term treatment but does not report its duration or provide long-term comparative results in the information.

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: Presented here is data from the Week 25 primary endpoint analysis. The study is ongoing.

Part 1: Double Blind (Weeks 1 - 24)

Reasons for not completing this period:

Part 2: Open Label (Weeks 25 - EoS)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The ITT Set consisted of participants who were randomized to a study treatment regimen.

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: The Intent-to-Treat (ITT) Set consisted of participants who were randomized to a study treatment regimen. Presented here are data from Part 1 baseline period.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR) at Week 25 Per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, measured over Baseline to Week 25 (Cycle 7, Day 1).

The primary endpoint is the objective response rate at Week 25 per RECIST Version 1.1. It is the percentage of participants who achieved either a complete response or a partial response, as judged by blinded independent radiologic review. A complete response requires disappearance of all target lesions, with pathological lymph nodes under 10 millimeter in short axis and non-nodal targets absent. A partial response requires at least a 30% decrease in the sum of target-lesion diameters from the baseline sum.

Response rate is used to summarize whether tumors meet prespecified imaging criteria for shrinkage or disappearance during the assessment period. Using blinded independent review helps separate the radiologic assessment from knowledge of assigned treatment. The endpoint is a binary classification at the assessment: each participant either meets the response definition or does not. It does not represent the average amount of shrinkage among all participants, nor does it describe how long a response lasts.

The endpoint also does not directly measure pain, stiffness, range of motion, or physical function. Those topics appear as secondary outcomes in the registry. A response result therefore answers a focused imaging question; interpreting the overall clinical picture requires attention to the other outcomes, safety information, and the limitations of the available registry results.

7. Results Posted in the Registry

• Vimseltinib: 39.8% (33/83) versus 0.0% (0/40) on control; risk difference 39.8 percentage points (95% CI 29.2 to 50.3); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

ORR at Week 25 Per Tumor Volume Score (TVS)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Vimseltinib: 67.5% (56/83) versus 0.0% (0/40) on control; risk difference 67.5 percentage points (95% CI 57.4 to 77.5); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Vimseltinib than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Active Range of Motion (ROM) at Week 25

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Vimseltinib: mean 18.40 versus 3.80 on control; difference 14.60 (95% CI -4.34 to 33.54), standardized effect d = 0.28; z-test p = 0.131.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Vimseltinib and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 25

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Vimseltinib: mean 4.60 versus 1.30 on control; difference 3.30 (95% CI 0.75 to 5.85), standardized effect d = 0.48; z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Vimseltinib than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes that extend beyond the primary imaging response, including tumor response by Tumor Volume Score, range of motion, physical function, stiffness, health status, and pain-related outcomes. The numerical secondary results described in the record include tumor response by Tumor Volume Score, range of motion, and PROMIS Physical Function. The other listed secondary outcomes do not have numerical results described in the registry record information available for this analysis.

At a broad level, the reported secondary outcomes offer measures that differ from RECIST response: one is another tumor-response assessment, while others concern movement or patient-reported function. This provides context for the primary result rather than simply repeating it. The secondary data should be considered alongside the primary imaging endpoint, but they do not have the same evidential status merely because they are listed in the trial record.

Unadjusted secondary results carry less weight because multiple outcomes create multiple opportunities to observe apparently notable findings by chance. General explanation: when many hypotheses are tested, the chance of at least one small p-value can increase unless the analysis plan accounts for multiplicity. The registry record does not report whether or how multiplicity was controlled for these secondary comparisons. Consequently, individual secondary p-values should be viewed as supportive or exploratory unless the prespecified testing hierarchy and multiplicity procedure are known.

The secondary outcomes also differ in scale, assessment method, and available participant counts. The numerical summaries alone do not establish whether a change is meaningful to participants or durable. The record does not provide enough information to assess all such questions, and numerical results for the other listed outcomes are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• ORR at Week 25 Per Tumor Volume Score (TVS)
• Change From Baseline in Active Range of Motion (ROM) at Week 25
• Change From Baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 25
• Change From Baseline in the Worst Stiffness Numeric Rating Scale (NRS) Score at Week 25
• Change From Baseline in EuroQoL Visual Analogue Scale (EQ-VAS) at Week 25
• Percentage of Participants With Response at Week 25 Based on Brief Pain Inventory (BPI) Worst Pain NRS Score and Narcotic Analgesic Use

9. Statistical Interpretation

10. Statistical Methods Explained

What does the response rate measure?

For this endpoint, response is defined using RECIST Version 1.1. A participant counts as a responder if the imaging review identifies complete response or partial response. Complete response concerns disappearance of target lesions under the stated lymph-node and non-nodal criteria. Partial response concerns a decrease in the sum of target-lesion diameters from baseline. The response rate is the percentage classified as responders in each group. It does not average the amount of change across responders and nonresponders.

The blinded independent radiologic review is relevant because tumor measurement involves assessment of imaging. Blinding is intended to limit the influence of treatment knowledge on the assessment. The registry names the review process but does not report further operational details, such as how disagreements between reviewers were resolved.

How should the group comparison be read?

The arm-specific response percentages describe outcomes within each randomized group. The difference in response rates compares those groups directly. In the sponsor’s reported analysis, the difference is 39.0 percentage points, with a 95% confidence interval from 28.4 to 49.6. The sponsor identifies the method as Cochran-Mantel-Haenszel. In general, this method compares categorical outcomes across strata, with a weighted overall comparison. The strata used for this trial are not reported in the registry record, so the weighting and any stratification factors cannot be described further.

The separate unadjusted recalculation uses the posted response counts and group sizes to form a simple risk difference and its confidence interval. It is not a substitute for the sponsor’s prespecified or full analysis. The recalculated p-value is p < 0.001, while the sponsor reports p < 0.001. These p-values arise from different analyses and should not be treated as interchangeable. The registry record does not indicate a discrepancy between the recalculation and sponsor analysis. The sponsor’s own analysis remains the relevant reported trial analysis.

What does a p-value say?

General explanation: a p-value describes how compatible data are with a specified null hypothesis under the statistical model and assumptions used. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an outcome. A small p-value does not remove uncertainty about the estimated effect, which is why the effect estimate and confidence interval are also important. The sponsor’s p-value accompanies its group comparison; the recalculated p-value accompanies a simpler unadjusted comparison.

Why do confidence intervals matter?

General explanation: a confidence interval gives a range of estimates compatible with the observed data under the chosen method and its assumptions. It conveys precision as well as direction. A narrower interval indicates less statistical uncertainty about the estimate than a wider interval, although precision does not resolve concerns about measurement, missing data, or applicability to other populations. The arm-level intervals and the interval for the difference answer distinct questions: one concerns each group’s response rate, while the other concerns the contrast between groups.

How should secondary continuous outcomes be interpreted?

The registry reports secondary changes in range of motion and PROMIS Physical Function using least-squares means and standard errors, with sponsor analyses identified as mixed model repeated measures. General explanation: a mixed model repeated measures approach can use repeated outcome measurements over time and account for the correlation among observations from the same participant. It can also estimate group differences while incorporating modeled time patterns. The registry record does not describe the exact model specification, covariance structure, covariates, or missing-data assumptions, so those features cannot be assessed from the reported method label alone.

The recalculated continuous comparisons use posted summary statistics and are simple unadjusted calculations. They should not be confused with the sponsor’s model-based estimates. For range of motion, the sponsor reports a least-squares mean difference of 14.6, with a 95% confidence interval from 4.0 to 25.3 and p = 0.008; the simple unadjusted recalculation has p = 0.131 and an interval that includes zero. For PROMIS Physical Function, the sponsor reports a difference of 3.3, with a 95% confidence interval from 1.4 to 5.2 and p < 0.001; the unadjusted recalculation has p = 0.011. Differences between these analyses can reflect their distinct methods and assumptions. The sponsor’s reported model-based analyses are the trial’s own results.

What are the planning illustrations?

General explanation: sample-size calculations estimate how many participants per arm a future study might need under specified assumptions about effect size, variability, significance level, allocation, and power. The registry’s planning illustrations use fractions of the observed effect and are not the trial’s original design justification. They are planning illustrations, not observed power and not evidence that the trial had a particular probability of detecting its result. The record states the assumptions for those illustrations; the trial’s own sample-size justification is not reported in the registry record.

Over-dispersion is a general concern for count or event data when variability exceeds what a simpler model assumes. The primary endpoint is a binary response percentage, and the record does not describe an over-dispersion adjustment for it. More generally, model assumptions affect standard errors and interval estimates, so reporting the analysis method and its assumptions is important. The registry does not provide enough detail to evaluate every modeling choice for the sponsor analyses.

11. Confidence Intervals and Precision

The primary arm-level estimates are 39.8% for vimseltinib and 0.0% for placebo. Their respective 95% confidence intervals are 29.2% to 51.1% and 0.0% to 8.8%. The sponsor’s interval for the difference in response rates is 28.4 to 49.6 percentage points. It is the interval for the between-group contrast that most directly describes uncertainty in the estimated difference.

General explanation: confidence intervals summarize statistical uncertainty under the chosen method and assumptions. They should not be read as a range that contains the true value with certainty, nor as a prediction interval for an individual participant. A confidence interval is also not a measure of clinical importance. That judgment requires considering what the endpoint means and how it relates to other outcomes.

The arm-specific interval for placebo extends above zero even though the observed response percentage is 0.0%. This is compatible with uncertainty about the underlying response rate when no responses are observed in the group. The interval for the group difference is separate and incorporates uncertainty in the comparison. The sponsor-reported difference interval does not include zero, while the recalculated unadjusted interval is expressed on the risk-difference scale as 0.292 to 0.503. The scales differ: the sponsor’s estimate is reported in percentage points, while the recalculation is recorded as a proportion.

The interval widths indicate that the estimated group response rates are not known with exact precision. The trial results support a clear observed contrast, but the plausible range of the contrast remains broader than a single point estimate. Precision is also specific to the Week 25 assessment and the reported analysis. The registry does not report additional interval estimates for long-term comparative outcomes or detailed sensitivity analyses that might show how estimates change under alternative assumptions.

12. Analyses Reported by the Sponsor

The sponsor reports a Cochran-Mantel-Haenszel comparison of the objective response rates: a difference of 39.0 percentage points, with a 95% confidence interval from 28.4 to 49.6 and p < 0.001. The registry classifies the result as superiority. This is the trial’s reported analysis and should be distinguished from a simple recalculation based on the posted group counts.

The unadjusted recalculation gives a risk difference of 0.398, with a 95% confidence interval from 0.292 to 0.503 and p < 0.001. These figures are on the proportion scale, while the sponsor’s result is expressed in percentage points. Both analyses indicate a difference favoring the vimseltinib group in the posted randomized comparison, but their estimates and p-values are not identical because the analyses are not the same. The recalculation is not a reconstruction of the sponsor’s method, and the registry does not report enough details about strata or other analysis specifications to reproduce that method.

The record indicates no discrepancy between the simple recalculation and the sponsor analysis. The sponsor’s result is therefore the appropriate reference for what the trial reported. The recalculation can serve as a transparent check using the posted summaries, but it should not replace the sponsor’s analysis or be interpreted as the trial’s full statistical model.

13. Multiplicity, Missing Data and Analysis Populations

The primary analysis population is the ITT Set, defined as participants randomized to a study treatment regimen. This is a clear population definition, but the registry record does not report further details on how missing Week 25 assessments were handled, how participants with incomplete imaging were classified, or whether any sensitivity analyses assessed alternative missing-data assumptions. Missing-data methods can affect response estimates if participants without an assessment are handled differently, so the absence of these details limits independent evaluation.

The registry lists six secondary outcomes, with numerical results described for only some of them in the available record. It does not report a multiplicity adjustment or a testing hierarchy for the secondary outcomes. General explanation: testing several outcomes can increase the chance of at least one apparently strong result under a setting where none of the tested effects is real. Prespecified ordering, adjusted significance thresholds, or other multiplicity procedures can address that issue, but whether such procedures were used is not reported in the registry record. The secondary findings should therefore not be treated as equivalent confirmatory evidence solely on the basis of their individual p-values.

The record identifies the sponsor’s primary categorical analysis as Cochran-Mantel-Haenszel but does not describe the strata, covariates, or detailed analysis population for that comparison. The record also identifies mixed model repeated measures for two continuous secondary analyses, without reporting model specifications or the missing-data assumptions used. These omissions do not invalidate the posted results, but they prevent a full independent reconstruction of the sponsor’s analyses from the registry information.

The registry lists an enrollment of 123, while the primary response summaries show group sizes of 83 and 40. The record does not explain all differences among analysis-specific group counts for other outcomes or safety summaries. The reported safety groups have different at-risk counts from the primary randomized groups, and one safety group is labeled “Total - Vimseltinib.” Those safety summaries should not be assumed to represent the same comparison population as the primary endpoint.

The trial’s sample-size justification, interim-analysis plan, and statistical analysis plan details beyond the methods identified in the outcome records are not reported in the registry record. The planning illustrations based on observed effects are not a substitute for those protocol details and are not observed power.

14. 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: cellulitis (3.4%), diarrhoea (2.6%), vomiting (2.6%), fall (1.7%), myocardial ischaemia (0.8%).

The registry safety summary lists serious adverse events for a group labeled “Total - Vimseltinib” and for placebo. Serious adverse events affected 17 of 118 at risk in the vimseltinib-labeled group and 1 of 39 at risk in the placebo group. Deaths are listed as 1 and 0, respectively. The record also reports other adverse events affecting 113 of 118 and 32 of 39 in those groups.

The “Total - Vimseltinib” label and its at-risk count differ from the primary randomized comparison. The safety figures should not be read as if they were the Week 25 response analysis or as if both groups necessarily represent the same period of randomized exposure. The registry summary describes placebo participants as able to receive open-label vimseltinib in Part 2, but does not provide enough detail to determine the exposure period represented by every safety count.

The listed serious adverse-event terms include cellulitis (3.4%), diarrhoea (2.6%), vomiting (2.6%), fall (1.7%), myocardial ischaemia (0.8%), and uveitis (0.8%). These are descriptive registry entries. The information does not establish that treatment caused an event, and the listed terms do not describe the full clinical context, timing, or severity for individual participants. Safety counts and event terms should be interpreted as reported, not as a causal comparison.

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

The primary result describes the percentage of randomized participants who met the imaging-based complete or partial response definition by Week 25. The posted response percentages were 39.8% for vimseltinib and 0.0% for placebo. The sponsor’s reported comparison estimated a difference of 39.0 percentage points, with a 95% confidence interval from 28.4 to 49.6. This is evidence of a difference in the trial’s defined response outcome during the blinded comparison.

The result does not mean that every participant receiving vimseltinib had a response, or that a participant without a RECIST response experienced no change in symptoms or function. It also does not establish how long a response lasts. The primary endpoint is an imaging classification at a specified assessment, not a complete measure of lived experience, disease course, or long-term outcome.

The comparison does not answer whether outcomes remain different after the placebo group can receive open-label vimseltinib. Part 2 is described as long-term open-label treatment, and the placebo-to-vimseltinib group may cross over after the blinded period. A continuing randomized placebo comparison in Part 2 is therefore not described. Long-term comparative conclusions are not reported in the registry record information.

The response result also does not resolve all questions about safety. The registry reports serious and other adverse-event counts, but those data are descriptive and the safety groups differ from the primary analysis groups. The record does not establish causality for listed events or provide enough detail to infer an individual participant’s risk.

Finally, statistical evidence is not the same as a determination of clinical importance for every patient or setting. The result should be interpreted alongside the endpoint definition, confidence intervals, secondary outcomes, safety information, and limitations in the reported analysis details. It is a finding from this randomized trial population and assessment period, not a guarantee of outcome for an individual or a substitute for clinical judgment.

16. Why This Trial Matters Statistically

This trial is statistically informative because it uses randomization and a blinded placebo comparison to assess a defined imaging endpoint. Randomization supports a group comparison by reducing the potential for systematic differences in treatment assignment, while blinding and independent radiologic review are relevant to outcome assessment. The primary result is reported with both arm-specific confidence intervals and a sponsor comparison interval, allowing readers to consider the estimated contrast and its uncertainty.

The registry also makes clear that the trial has more than one phase of treatment. The randomized placebo comparison occurs in Part 1, while Part 2 is open-label and allows placebo-assigned participants to receive vimseltinib. This distinction matters when interpreting which period supports a controlled comparison and which is intended as longer-term treatment. A crossover design can be useful for access to active treatment, but it changes the interpretation of later between-group comparisons.

The trial’s secondary outcomes broaden the statistical questions beyond tumor imaging, including physical function and range of motion. Their interpretation depends on their own measurement properties and analysis models, and unadjusted testing across multiple outcomes warrants caution. The registry record gives some but not all of the information needed to assess the full statistical plan.

For biostatistical interpretation, the case illustrates why the reported sponsor model, a transparent summary-based recalculation, confidence intervals, outcome hierarchy, analysis population, missing-data handling, and multiplicity procedures should be distinguished. Those elements answer different questions. The posted result is most informative when its endpoint and analysis period are kept in view and when the unreported protocol details are not filled in by assumption.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several details needed for a full assessment are not reported in the registry record. The protocol’s sample-size justification, interim-analysis plan, and complete statistical analysis plan are not described. The record identifies the sponsor’s methods but does not provide enough detail to reproduce the Cochran-Mantel-Haenszel comparison, including the strata used. For the mixed model repeated measures analyses, the model specification, covariance structure, covariates, and missing-data assumptions are not reported.

The registry record does not explain how missing primary endpoint assessments were handled or provide sensitivity analyses for missing data. It also does not report a multiplicity procedure or testing hierarchy for the secondary outcomes. These gaps limit evaluation of how robust results are to analytic choices and how confirmatory the secondary findings should be considered.

The primary result is tied to a Week 25 imaging assessment and a specific response definition. It does not describe response duration or long-term comparative outcomes. Because the placebo group could receive open-label vimseltinib in Part 2, later treatment comparisons may not retain the same randomized contrast. The long-term phase is described, but its duration and comparative results are not reported in the registry information.

The safety summaries use at-risk counts that differ from the primary randomized groups, including a combined “Total - Vimseltinib” label. The registry entries do not fully explain the exposure periods represented by these groups. Safety event counts are descriptive and do not, by themselves, establish causal attribution. Numerical results for several listed secondary outcomes are also not reported in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Study of Vimseltinib for Tenosynovial Giant Cell Tumor — NCT05059262.
• Registry record last updated 2026-03-20; status last verified 2026-03.
• Results first posted 2025-02-24.
• 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.

21. Record Summary

The registry describes MOTION, a Phase 3 randomized, placebo-controlled, double-blind study of vimseltinib for tenosynovial giant cell tumor. Part 1 compared blinded vimseltinib with matching placebo for 24 weeks; Part 2 provided open-label vimseltinib. The primary endpoint was objective response rate at Week 25 by RECIST Version 1.1, assessed through blinded independent radiologic review in the ITT Set.

The reported response rates were 39.8% for vimseltinib and 0.0% for placebo. The sponsor reported a difference of 39.0 percentage points (95% confidence interval 28.4 to 49.6; p < 0.001). The registry lists secondary outcomes and safety summaries, but some analysis details, missing-data methods, multiplicity procedures, and numerical results for several outcomes are not reported in the registry record.