Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma (NCT05943990), a na phase 1 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a phase 1 study of GSK3845097, sponsored by Adaptimmune. Its stated focus was previously treated participants with advanced synovial sarcoma or myxoid/round cell liposarcoma whose tumors met the NY-ESO-1 and/or LAGE-1a target criteria and who had the specified HLA-A types. The study record describes a single-group model, no masking and allocation listed as NA. These features do not establish a randomized comparison.

The record lists an enrollment of 5. Study start was 2020-12-21, primary completion was 2022-10-24, and the status is terminated. The reason for termination and whether all enrolled participants completed study procedures are not reported in the registry record. The record lists GSK3845097, cyclophosphamide and fludarabine as interventions. It describes leukapheresis to manufacture engineered T cells followed by lymphodepleting chemotherapy and GSK3845097.

The aim was to assess safety and tolerability and determine a recommended phase 2 dose. The primary endpoint was DLT count up to 28 days. Secondary outcomes named in the record include investigator-assessed overall response rate according to RECIST v1.1, duration of response and measures of transgene expansion. The registry does not report outcome estimates or analyses for these endpoints. Dose-level groups appearing in the adverse-event record do not change the overall design classification or establish that dose groups were assigned randomly.

For interpreting the evidence, the small enrollment and absence of a randomized comparator matter. Descriptive counts can document what the registry lists for these participants, but they cannot by themselves distinguish treatment effects from other explanations. Details such as a dose-escalation scheme, stopping rules and the reason for termination are not reported in the registry record.

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 is a sub study of the master protocol (NCT04526509). This sub study was terminated due to a change in GSK's R\&D priorities.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT Evaluable included participants in the mITT population (all ITT participants (All participants who started leukapheresis procedure) who received any dose of New York esophageal antigen-1 \[NY ESO 1\] specific T cells) who are part of the dose confirmation phase that either had a DLT or have completed the DLT assessment period of 28 days since last T cell infusion.

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 Number of Participants With Dose Limiting Toxicities (DLTs), measured over Up to 28 days.

The primary endpoint is the number of participants with dose-limiting toxicities, assessed up to 28 days. A DLT is a protocol-defined safety event used to characterize whether a treatment dose produces toxicities considered important during the specified assessment period. In a study intended to determine a recommended phase 2 dose, this kind of endpoint can inform dose selection by focusing attention on serious or persistent toxicities rather than treating every event as equivalent.

The registry defines DLTs using toxicity grades and attribution to GSK3845097, along with specified duration or resolution criteria. The definition includes related Grade 4 toxicity; certain Grade 3 toxicity that does not resolve within 7 days; specified pneumonitis, cytokine release syndrome and neurotoxicity criteria; and qualifying major-organ toxicity within 28 days of infusion. The description refers to NCI-CTCAE v5.0 grading. These definitions determine which events count toward the endpoint; the endpoint is not simply the number of all adverse events.

A participant count is a descriptive safety measure. It does not express the event rate over time, severity distribution or comparative risk unless those are separately reported. The registry record gives the endpoint definition and timeframe but does not report the DLT count or a resulting recommended phase 2 dose. Therefore the endpoint’s observed result cannot be interpreted from the posted registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish the question a study was designed to address from the conclusions that its data can support. In this case, the primary question is safety-focused: count participants meeting a prespecified DLT definition within the stated timeframe. The registry record gives the endpoint definition, but does not report a DLT result or the analysis used to summarize it. No inferential result is available for interpretation.

What does a participant count show?

A count reports how many participants met an outcome definition. For a binary endpoint such as whether a participant experienced a DLT, the count alone does not convey how precisely the underlying frequency is estimated. Precision depends in part on the number of participants assessed and on how completely their outcomes were observed. A confidence interval, when reported, describes uncertainty around an estimate under the method used; it does not guarantee that the estimate is correct or remove bias from study design. No confidence interval for DLTs is reported in the registry record.

Counts also need a clearly defined denominator. The DLT outcome is specified for a DLT-evaluable population, while enrollment is listed as 5. Those are not necessarily interchangeable populations. The record describes DLT-evaluable participants in terms of participants in the mITT population who were part of the dose confirmation phase and either had a DLT or met a further condition; that final condition is incomplete in the record. Consequently, the complete denominator definition cannot be reconstructed. The number of participants actually evaluated for DLTs is not reported in the registry record.

Why does the design affect interpretation?

A randomized comparison aims to make treatment groups comparable through assignment, supporting a causal contrast when other design and analysis conditions are met. This study is recorded as single-group, with allocation NA and no masking. The adverse-event data nevertheless list different dose groups and a no-treatment group. Their presence does not make the study randomized, and a contrast between their counts would not have the same interpretation as a randomized treatment comparison. In a non-randomized setting, group membership and other differences can affect outcomes, and the registry does not report an adjusted comparative analysis.

Masking concerns whether participants, investigators or outcome assessors know the assigned intervention. The record states that masking was none. For a safety endpoint that includes graded and attributed toxicities, knowledge of treatment could potentially influence assessment or attribution. This is a general methodological consideration, not evidence that assessment was biased in this study. The registry does not report procedures to reduce assessment bias.

What do the planning assumptions mean?

A planning illustration based on an observed effect is not a trial design justification and is not observed power. The described calculation assumptions are a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such an illustration depends on the observed effect estimate and on its assumptions; it does not show that a study with that sample size would have achieved a particular result. The registry record does not report the trial’s own sample-size justification or a design based on these assumptions. It also does not report a numerical observed effect or a sample-size result in the information available for interpretation.

Normal approximations use a simplified model for the sampling distribution of an estimate. General statistical practice treats these approximations cautiously when data are sparse, because the model may not represent the actual distribution well. With a very small enrollment, counts can change substantially in meaning with each participant, and uncertainty is inherently important. No model-based estimate, uncertainty interval or analysis diagnostics are reported in the registry record.

How should multiple outcomes be understood?

The registry names secondary outcomes, including response, duration of response and transgene expansion measures. Each outcome addresses a different question and may have a different analysis population, observation period and data structure. If many outcomes are tested, the chance of at least one apparently notable result can rise unless the analysis accounts for multiplicity. This is a general statistical issue; it does not establish that any particular result is false. Multiplicity procedures, endpoint hierarchy and prespecified analysis methods are not reported in the registry record. Nor are statistical methods for handling missing observations, censoring or repeated measurements reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("GSK3845097 1 × 10^9 - 8 × 10^9 Transduced Cells", "GSK3845097 0.1 × 10^9 - 0.8 × 10^9 Transduced Cell")
n      <- c(2, 2)
events <- c(1, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  GSK3845097 1 × 10^9 - 8 × 10^9 Transduced Cells  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6
ARM  GSK3845097 0.1 × 10^9 - 0.8 × 10^9 Transduced Cell  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary DLT outcome and names secondary outcomes, including investigator-assessed overall response rate according to RECIST v1.1, duration of response and transgene expansion measures. It does not report a multiplicity strategy, such as a hierarchy among endpoints or an adjustment for testing multiple outcomes. The intended statistical analysis plan is not reported in the registry record. Without those details, it is not possible to tell how the study intended to control the interpretation of multiple outcome analyses.

Missing-data methods are also not reported in the registry record. The record does not explain how missing endpoint assessments, incomplete follow-up or participants who did not meet an evaluable-population definition were to be handled. This matters because the primary endpoint is defined for DLT-evaluable participants, while enrollment is separately listed as 5. The actual number evaluated and the reasons for any exclusions or missing assessments are not reported.

The outcome description refers to an ITT population as all participants who started leukapheresis and an mITT population as those who received any dose of NY-ESO-1 specific T cells. The DLT-evaluable definition further refers to mITT participants in the dose confirmation phase who had a DLT or met an additional condition, but that final part of the definition is incomplete in the registry record. No counts for these analysis populations are reported. The distinction between enrolled, treated and evaluable participants therefore cannot be resolved from the posted information.

The registry record lists no analysis results. It does not report whether any planned analyses were changed, whether outcomes were analyzed as described, or how participants in the no-treatment group related to the primary analysis population. These absences limit assessment of the analysis strategy and should not be filled by assuming standard practices.

12. 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: pyrexia (50.0%), systemic inflammatory response syndrome (50.0%), febrile neutropenia (50.0%), aplastic anaemia (50.0%), pancytopenia (50.0%).

The serious adverse-event record lists three groups. For GSK3845097 1 × 10^9 - 8 × 10^9 Transduced Cells, it lists 2 at risk, 1 affected and 0 deaths. For GSK3845097 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells, it lists 2 at risk, 2 affected and 2 deaths. For No Treatment, it lists 1 at risk, 0 affected and 0 deaths. These are descriptive registry counts. They do not establish that an intervention caused an event or death.

The listed serious adverse-event terms are pyrexia, systemic inflammatory response syndrome, febrile neutropenia, aplastic anaemia, pancytopenia and thrombocytopenia, each reported as 50.0%. The registry record does not report the denominator or the relationship between these terms and the group-level affected counts. Terms may overlap within participants; the percentages should not be added or treated as distinct participant counts.

Interpretation is limited by the small group sizes, absence of random allocation and lack of reported detail on event timing, duration, attribution, follow-up and missing safety data. The deaths are important entries to note, but the record does not state their causes or relationship to study treatment. These figures describe what the registry lists and do not, by themselves, support a causal safety comparison.

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

The record establishes that a phase 1 study was undertaken to assess the safety and tolerability of GSK3845097 and determine a recommended phase 2 dose in a selected population with advanced synovial sarcoma or myxoid/round cell liposarcoma. It also establishes the primary endpoint definition and timeframe, the listed interventions, enrollment of 5 and the terminated status. These are details about the study’s design and registry status, not evidence of a particular safety or efficacy outcome.

The primary endpoint result is not reported in the registry record. The number of participants with DLTs and the resulting recommended phase 2 dose are therefore unknown from the posted information. Although secondary outcomes are named, response and other outcome results are not reported. The study record consequently does not establish an estimate of antitumor activity or a comparative treatment effect.

Serious adverse-event figures and listed terms offer descriptive information, but they should not be interpreted as proof of causation. The groups are small and not a randomized comparison, and the record does not include the context needed to relate deaths or events to treatment. Likewise, the listed no-treatment group is not evidence of a like-for-like control group.

These limitations do not mean the study had no findings; they mean the registry information does not report the information needed to evaluate those findings. The reason for termination, the full analysis populations, missing-data handling, multiplicity procedures and statistical plan are not reported in the registry record. Conclusions should remain bounded by what is actually recorded: a small phase 1 study with a safety and dose-selection aim, but without posted primary-endpoint or analysis results.

14. Why This Trial Matters Statistically

This trial is statistically notable because its stated purpose is dose selection and safety characterization rather than a randomized efficacy comparison. DLT counts can be relevant to choosing a dose for later investigation, but their interpretation depends on a clear evaluable population, a prespecified toxicity definition and complete reporting of observed events. The registry provides the DLT criteria and timeframe, but does not report the observed count or the recommended phase 2 dose.

The study also illustrates why design labels matter. The record describes a single-group model and no masking, while safety information is organized by dose range and includes a no-treatment group. Those group labels do not create randomized comparability. Statistical contrasts across small, non-randomized groups can be difficult to interpret because observed differences may reflect factors other than treatment.

Enrollment of 5 makes transparent reporting of participant flow and denominators especially important. Counts, evaluable populations and missing outcome assessments should be distinguishable. The registry’s DLT-evaluable description is incomplete, and the actual number evaluated is not reported. This prevents readers from connecting the endpoint definition to its intended analysis population.

Finally, the record names multiple outcomes but does not report statistical methods or results. Without a stated analysis plan, multiplicity approach and endpoint findings, readers cannot assess how the study’s several questions were addressed. The example underscores that trial registration details are useful for understanding intended methods, while a complete interpretation requires clear posting of analyzed outcomes and their uncertainty.

15. 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 uncertainties. The study is marked terminated, but the reason for termination is not reported. It is also not reported whether termination occurred after planned follow-up, whether recruitment ended early, or how termination affected outcome collection. No inference about the cause or implications of termination can be made from status alone.

The enrollment is 5, while the adverse-event record separates participants into groups with 2, 2 and 1 at risk. The registry does not describe how these groups were formed, how dose assignment occurred or how the no-treatment group relates to the study’s main treatment objective. Allocation is listed as NA, so these categories should not be treated as randomized arms. Follow-up duration for the safety summaries, apart from the primary endpoint’s up to 28 days timeframe, is not reported.

The primary outcome is defined in detail, but its result is absent. The full DLT-evaluable population description is incomplete, and the number of participants meeting that definition is not reported. The registry also does not report DLT attribution, individual event timing or the recommended phase 2 dose. Secondary outcomes are named without posted estimates or analysis results.

For safety, the record lists affected counts, deaths and serious-event terms, but does not report causes of death, event-level attribution, term denominators or whether the listed terms overlap within participants. Missing-data handling and completeness of follow-up are not reported. These limitations preclude a precise causal or comparative assessment of the safety entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma — NCT05943990.
• Registry record last updated 2024-11-13; status last verified 2024-11.
• Results first posted 2024-03-18.
• 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.

19. Record Summary

NCT05943990 is a phase 1, single-group study of GSK3845097 in previously treated participants with advanced synovial sarcoma or myxoid/round cell liposarcoma. The record lists Adaptimmune as sponsor, enrollment of 5, study start on 2020-12-21, primary completion on 2022-10-24 and status as terminated. It describes autologous engineered T cells targeting NY-ESO-1 and LAGE-1a, with cyclophosphamide and fludarabine also listed as interventions.

The primary outcome is the number of participants with DLTs up to 28 days, intended to support assessment of safety and determination of a recommended phase 2 dose. The registry lists dose-group safety counts and serious-event terms but does not report a primary endpoint result, the recommended dose, secondary outcome estimates or statistical analyses. The reason for termination, analysis plan, missing-data methods and complete DLT-evaluable population definition are not reported in the registry record.