BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST) (NCT02257541), a na phase 1, phase 2 study. The primary outcome is Phase Ib Study: Number of Participants With Dose-Limiting Toxicities.

2. Clinical Question

The study’s stated purpose was to evaluate the safety of giving BGJ398 with imatinib and to identify doses for the combination. The brief summary describes a Phase Ib dose-finding portion followed by a larger Phase II study once a dose had been determined to be safe. The record identifies a secondary outcome, response rate in the Phase Ib study, but does not report its result.

Statistically, the primary question is descriptive: it concerns the number of participants meeting the dose-limiting-toxicity definition, rather than a difference between treatments. Without a control group, the record cannot establish a treatment contrast against imatinib alone, another regimen, or no treatment. The listed dose levels describe study groups in the dose-finding portion, not comparable groups created through random assignment.

3. Trial Design

The registry lists a Phase Ib/II study of BGJ398 combined with imatinib mesylate in patients with untreated advanced GIST. The study is marked completed, with enrollment of 16. Its start date is 2014-10-02 and its primary completion date is 2019-03-25. These record-level details describe the study, but do not establish how many participants completed treatment or contributed to any particular analysis.

The design is listed as single-group, with allocation recorded as not applicable and masking listed as none. There was no randomized control arm. The Phase Ib portion is described as using standard 3+3 dose escalation, based on toxicities encountered during the first cycle of therapy. The arm description gives imatinib at 400 mg once daily and describes BGJ398 dose escalation on treatment schedule A, with 21 days on treatment and 7 days off. Additional dosing details are not reported in the registry record.

The brief summary describes a planned progression from dose finding to a Phase II study after a dose was determined to be safe. The record includes dose-level groups and a Phase II group in its adverse-event data. It does not report the criteria or decision process used to move between portions, the number of participants assigned to each portion, or the extent to which the stated plan was carried out.

Because there is no randomized comparator, differences between the listed dose-level groups should not be read as causal treatment effects. Dose levels may reflect the study’s escalation process, and the groups are not reported as being formed to provide a like-for-like comparison. The registry record does not report a detailed statistical analysis plan, sample-size justification, interim analyses, or a prespecified method for comparing dose levels.

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.

Overall Study

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 Phase Ib Study: Number of Participants With Dose-Limiting Toxicities, measured over 1 year.

The primary endpoint is the number of participants with dose-limiting toxicities in the Phase Ib study. A dose-limiting toxicity is used in dose-finding research to identify treatment-related toxicity that is considered important for decisions about whether a dose can be taken forward. In a dose-escalation design, toxicity observations help guide assessment of dose levels. The registry record describes the Phase Ib portion as following a standard 3+3 format and says that the assessment is based on toxicities during the first cycle of therapy.

The endpoint is a count of participants, not a count of all individual toxicity episodes. A participant-level count can answer how many people met the endpoint definition, but by itself does not describe the number, severity, duration, or clinical course of every event. Those details would require further outcome definitions and results, which are not reported in the registry record.

There is a timing detail to note: the endpoint timeframe is listed as 1 year, while its description says that the Phase Ib assessment is based on toxicities during the first cycle. The registry record does not explain how these two time descriptions relate. It also does not report the operational definition of a dose-limiting toxicity, the primary endpoint count, or a statistical estimate such as a confidence interval. Therefore, the endpoint’s intended role can be described, but the observed primary result cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

The registry lists this study as single-group, with no randomized comparator. In general, a single-group study can describe outcomes observed among participants who receive the study regimen. It cannot directly separate the regimen’s effect from other explanations for those outcomes, because there is no concurrent control group to anchor a treatment contrast. For this study, the registry’s design details support descriptive interpretation, not a randomized comparison of BGJ398 plus imatinib against another regimen.

The dose levels should be understood within the stated dose-finding design. The record describes the Phase Ib portion as using a standard 3+3 format, with decisions based on toxicities during the first cycle. In general, a 3+3 design evaluates toxicity within dose cohorts and uses observed toxicity to inform dose escalation decisions. The registry record does not provide a complete protocol, decision rules, or a final dose-selection result, so those details should not be inferred from the design label alone.

What does a participant count mean?

The primary endpoint is a count of participants with dose-limiting toxicities. In general, a participant-level binary outcome classifies each person as either meeting or not meeting a stated event definition within the relevant observation period; the count records how many meet it. That count is distinct from a count of toxicity episodes, since one participant could experience more than one event. The registry record does not report the primary endpoint count or fully define the dose-limiting-toxicity criteria.

The endpoint’s timeframe is listed as 1 year, while its description ties the Phase Ib assessment to the first cycle. A clear observation window matters because a participant’s classification depends on when events are counted and how the event definition is applied. The registry record does not clarify the relationship between those timing statements. It also does not report how participants with incomplete follow-up or missing toxicity assessments were handled.

How should uncertainty be considered?

General statistical explanation: a confidence interval expresses the uncertainty around an estimated quantity under a statistical model. For a count or proportion based on a small group, uncertainty can be substantial; a single additional event may meaningfully change the estimate. Reporting an interval alongside an estimate can make that imprecision visible. No confidence interval for the primary endpoint is reported in the registry record, and there is no result from which to interpret one.

General statistical explanation: an analysis should identify its population, outcome definition, observation window, and method. Those elements determine what an estimate represents. Here, enrollment is recorded as 16, but the analysis population for the primary outcome is not reported in the registry record. The counts at risk in the adverse-event data are group-specific and should not be treated as a substitute for a stated primary-outcome analysis population.

What do the adverse-event counts describe?

The registry separates serious adverse-event counts from counts for other adverse events in the listed groups. These are descriptive safety data. In general, adverse-event summaries depend on clear definitions, observation periods, and denominators. A count among participants at risk does not, on its own, provide a complete account of event timing, duration, severity, or attribution to treatment. The registry record does not give all of those details for the posted group counts.

The listed serious-event terms include percentages, but the record does not make clear in the registry record what denominator applies to each term or whether participants could contribute to more than one term. Those percentages should not be combined, summed, or interpreted as mutually exclusive categories. The group-level counts and the named terms are different descriptions and do not establish the primary dose-limiting-toxicity result.

What do the planning assumptions mean?

The accompanying planning illustration is described as based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It is further described as targeting a stated fraction of the observed effect. These are planning assumptions, not findings from a randomized two-arm comparison in this study. The registry design is single-group, and the registry entries do not report the observed effect used in the illustration or any resulting sample-size values.

In general, a sample-size calculation estimates the number of participants needed under specified assumptions about the effect to detect, variability, allocation, and statistical error. It does not report how many participants were observed, and it is not observed power. A planning calculation based on an observed effect is particularly dependent on that effect estimate and the assumptions used. No study-specific sample-size justification or protocol calculation is reported in the registry record. The record also does not report interim analyses or a detailed statistical plan.

What analyses are available?

The registry record lists zero analyses. That means no inferential analysis is available in the posted record for interpretation. The record does not report a test comparing dose levels, an adjusted analysis, a primary endpoint estimate, or a confidence interval. No method should be attributed to the study beyond what is explicitly recorded. General methods can explain how such results might be interpreted, but they cannot fill in missing estimates or analysis details.

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("Phase 1b, Dose Level -1", "Phase 1b, Dose Level 1", "Phase 1b, Dose Level 2", "Phase 1b, Dose Level -2")
n      <- c(3, 8, 1, 3)
events <- c(3, 8, 1, 3)
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  Phase 1b, Dose Level -1  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Phase 1b, Dose Level 1  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  Phase 1b, Dose Level 2  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Phase 1b, Dose Level -2  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and a secondary outcome, but does not report a multiplicity strategy. Multiplicity concerns arise when investigators evaluate several outcomes, groups, time points, or comparisons and make inferential claims across them. In general, a prespecified approach can clarify which findings are confirmatory and how the chance of false-positive conclusions is managed. The record does not report whether any such approach was planned or used.

The primary outcome result is not reported, and the named secondary outcome, Phase Ib response rate, also has no reported result. The registry lists zero analyses. It does not provide an analysis population, missing-data method, or account of participants with incomplete outcome information. Enrollment of 16 should not be assumed to equal the number analyzed for any endpoint.

The endpoint description says dose-limiting toxicity assessment is based on toxicities during the first cycle, while the listed timeframe is 1 year. The record does not explain the relationship between these periods or how events and follow-up were handled. It also does not report a plan for participants who were not evaluable within the stated period. These omissions limit assessment of how complete or comparable the endpoint data are.

In general, missing-data handling can affect both the number analyzed and the interpretation of an estimate, especially when the reasons for missingness relate to outcome or treatment. That general concern cannot be resolved for this study from the registry record. The record also does not report whether an intention-to-treat, treated-participant, or evaluable-participant analysis population was used. Therefore, no particular analysis population or missing-data assumption should be attributed to the study.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: intra-abdominal bleeding (100.0%), cpk increased (33.3%), hypertension (33.3%), ejection fraction decreased (33.3%), lipase increased (33.3%).

The adverse-event record lists five groups: Phase 1b dose levels -1, 1, 2, and -2, plus Phase II. For each group, it reports participants at risk and participants affected for serious adverse events and for other adverse events, as well as deaths. For dose level -1, the serious-event count is 2 of 3 at risk, the other-event count is 3 of 3, and deaths are 2. For dose level 1, the corresponding counts are 7 of 8, 8 of 8, and 3 deaths. For dose level 2, they are 1 of 1, 1 of 1, and 0 deaths. For dose level -2, they are 3 of 3, 3 of 3, and 0 deaths. In Phase II, they are 0 of 1, 1 of 1, and 0 deaths.

These are descriptive counts in the registry record. The dose-level groups are not randomized control arms, and the group sizes vary. The counts do not establish whether an event was caused by treatment, nor do they show event timing, duration, or severity beyond the serious/other classification. The record does not explain the relationship between these adverse-event categories and the primary dose-limiting-toxicity definition.

The record also lists serious-event terms with percentages, including Intra-Abdominal Bleeding at 100.0%. The denominator for each term and whether terms overlap are not reported in the registry record. Those percentages should therefore be read as registry-listed descriptive values, not as a complete participant-level risk estimate or a basis for comparing groups.

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

The study addresses a dose-finding and safety question for BGJ398 combined with imatinib in untreated advanced GIST. Its Phase Ib portion was described as using toxicity observations during the first cycle within a standard 3+3 format. This design description explains the intended role of the study: to examine toxicity across dose levels and inform dose selection. It does not reveal the observed primary endpoint result.

The record does not report how many participants had dose-limiting toxicities, the dose selected for further study, or the Phase Ib response-rate result. It therefore cannot establish from the posted data what dose was considered acceptable, how often the primary endpoint occurred, or what response was observed. The completed status and listed enrollment do not replace those missing outcome results.

The adverse-event data provide counts by listed groups, but they are not a controlled comparison. Some groups have very few participants at risk, and the record does not report an adjusted analysis. Differences in these counts should not be interpreted as evidence that one dose level is safer or more harmful than another. Nor should serious adverse events be treated as equivalent to dose-limiting toxicities without a reported definition linking the outcomes.

More generally, the design cannot isolate a causal effect of the combination from other influences because it has no randomized comparator. A single-group result can describe what was observed in the study population, but it cannot by itself determine what would have occurred under a different treatment. The record also does not provide enough information to assess the completeness of endpoint follow-up or the analysis population.

The defensible conclusion is limited: the registry describes a completed single-group Phase Ib/II study, states its dose-finding rationale and primary endpoint, and posts some group-level adverse-event counts. It does not report the primary outcome result or the named secondary response-rate result. Any conclusion about comparative safety, efficacy, or a treatment effect would go beyond the information in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why design and outcome reporting must be considered together. A dose-finding study has a different statistical purpose from a randomized comparison. Its central question is whether toxicity observations across dose levels support further evaluation of a regimen, rather than whether one treatment outperforms a control. The registry’s single-group designation and absence of a comparator are therefore essential to interpreting its results.

The endpoint also shows the importance of a precise definition and observation window. The primary outcome is a participant count for dose-limiting toxicities, and the description refers to toxicities during the first cycle. The listed timeframe is 1 year. Without clarification of how these statements fit together, readers cannot fully determine the period over which participants were classified or how the endpoint was applied.

Small, dose-specific groups make transparent reporting especially important. In general, sparse counts can be imprecise, and group-level counts do not automatically support a reliable contrast. A complete account would help readers understand who was analyzed, which endpoint criteria were used, how dose decisions were made, and what uncertainty surrounds the estimates. Those details and the primary endpoint result are not reported in the registry record.

The record also demonstrates the difference between a planning calculation and observed evidence. The stated planning assumptions describe a hypothetical two-arm framework, whereas the trial itself is listed as single-group. A planning illustration can be useful for future study design, but it is not a comparison conducted in this trial and is not observed power.

For biostatisticians and clinical researchers, the key statistical lesson is that a design label, an endpoint definition, an analysis population, and an observed result each answer different questions. When the result and analysis details are absent, careful interpretation means describing what is recorded without supplying conclusions the record cannot support.

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.

Several trial-specific limitations arise from the registry record. First, the primary endpoint result is not reported, despite the endpoint being defined as the number of participants with dose-limiting toxicities. The secondary Phase Ib response-rate result is also not reported. The registry lists zero analyses, so there is no posted estimate or inferential result to evaluate.

Second, the endpoint timing is not fully clear. The timeframe is listed as 1 year, but the description says that Phase Ib toxicity assessment is based on the first cycle of therapy. The record does not reconcile these statements, describe the dose-limiting-toxicity criteria, or report how incomplete follow-up was handled.

Third, the design is single-group, without randomized allocation or a comparator. The dose-level groups are not like-for-like control groups, and group differences cannot be interpreted as causal effects. The record does not provide an adjusted comparison or the analysis plan needed to assess how the dose-level data were evaluated.

Fourth, enrollment of 16 does not identify the analysis population. The record does not say how many participants were evaluable for the primary endpoint, whether all enrolled participants received treatment, or how missing data were handled. The adverse-event entries provide group-specific at-risk counts, but do not resolve these questions for the primary endpoint.

Finally, some adverse-event terms are reported with percentages without a clear denominator or information on overlap. The arm description is also incomplete. Sample-size justification, interim analyses, and a detailed statistical plan are not reported in the registry record. These limitations mean the posted information supports a description of design and selected safety counts, not a complete assessment of the study’s outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST) — NCT02257541.
• Registry record last updated 2020-03-30; status last verified 2019-03.
• Results first posted 2020-03-30.
• 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

The registry record describes a completed Phase Ib/II, single-group study of BGJ398 with imatinib mesylate in untreated advanced GIST. Enrollment is listed as 16. The Phase Ib portion is described as standard 3+3 dose escalation based on toxicities during the first cycle. The primary endpoint is the number of participants with dose-limiting toxicities, with a listed timeframe of 1 year; the primary result is not reported.

The record names Phase Ib response rate as a secondary outcome but does not report its result. It posts adverse-event counts across dose-level groups and Phase II, without a randomized comparator. The analysis population, missing-data handling, detailed statistical plan, and sample-size justification are not reported in the registry record. Accordingly, the available information supports a description of study design and posted safety counts, but not conclusions about comparative effects or the unreported primary outcome.