BGJ398 for Patients With Tumors With FGFR Genetic Alterations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BGJ398 for Patients With Tumors With FGFR Genetic Alterations (NCT02160041), a na phase 2 study. The primary outcome is Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of BGJ398 in patients with tumors with FGFR genetic alterations. The record describes its purpose as signal seeking: to determine whether treatment showed sufficient efficacy in select FGFR pathway-regulated solid tumors and/or hematologic malignancies to warrant further study. That purpose is distinct from a confirmatory comparison of treatments. Allocation is recorded as NA, masking as none, and the model as single group. No like-for-like control arm is listed.

The study enrolled 84 participants. The registry record lists solid tumor and hematologic malignancies as conditions. The Full Analysis Set included enrolled patients who received at least 1 dose of study drug and was the primary set for efficacy analyses. The description of the solid-tumor clinical benefit rate specifies an assessment excluding 3 TIO and 1 Lymphoma patients, hence 80 patients rather than 84. The record does not provide a complete participant flow or explain the status of every enrolled participant in relation to treatment and endpoint assessment.

BGJ398 was administered at 125 mg once daily during the first 21 days of each 28-day cycle, with 1 week off. The record defines a complete treatment cycle as 28 days. The primary endpoint was clinical benefit rate associated with treatment, with a 16-week timeframe. The record also lists overall response, progression-free survival, overall survival, Kaplan-Meier estimates, and duration of response among secondary outcomes.

The listed study start date is 2014-07-24 and the primary completion date is 2018-04-30. The study status is terminated. The reason for termination and any changes to the study plan are not reported in the registry record. The sponsor is Novartis Pharmaceuticals. No randomized comparison, masking, or comparator outcome is described, so treatment outcomes should be interpreted as observations from a single-group study rather than as an estimate of a comparative treatment effect.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): The FAS included all enrolled patients who received at least 1 dose of study drug. The FAS was the primary set for efficacy analyses.

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: Full Analysis Set (FAS): The FAS included all enrolled patients who received at least 1 dose of study drug. The FAS was the primary set for efficacy analyses.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment, measured over 16 weeks.

The primary endpoint is the clinical benefit rate associated with BGJ398 treatment, assessed at 16 weeks. For solid tumors, the record defines clinical benefit as a complete response, partial response, or stable disease, assessed using RECIST 1.1. It describes complete response as disappearance of all target lesions and partial response as a decrease of at least 30% in the sum of the longest diameters of target lesions. The record also includes a separate description referencing RECIST v1.0 for target lesions assessed by MRI, with overall response defined as complete response plus partial response. The registry record does not clarify the relationship between these RECIST references.

A clinical benefit endpoint combines tumor shrinkage with stable disease, so it captures a broader set of outcomes than response alone. In general, this can be useful in a signal-seeking study when the question is whether disease control is observed, rather than whether tumors shrink. The endpoint is a participant count, and its interpretation depends on the specified population, assessment criteria, and assessment time. The record says that other appropriate hematological response criteria may apply to hematologic tumors, but does not specify those criteria. It does not report the observed endpoint count or rate, or the numbers with complete response, partial response, and stable disease. Thus, the endpoint definition is available, but the magnitude and precision of the observed clinical benefit cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical benefit rate is a binary endpoint at the participant level: each assessed participant either meets the endpoint definition or does not. For the solid-tumor population, the registry record defines benefit as complete response, partial response, or stable disease. In general, a binary endpoint is summarized by a count and a proportion, with the denominator tied to the population actually assessed. The record supplies the endpoint definition and the stated solid-tumor population of 80 patients, but does not report the number meeting the definition or a corresponding proportion. No new estimate can be reconstructed from the information in the registry record.

What does the endpoint definition capture?

Complete response and partial response are response categories; stable disease adds participants whose disease does not meet either response category but is not classified as progression under the relevant criteria. Combining these categories creates a broader disease-control endpoint than response alone. In general, this can suit a signal-seeking question when the aim is to identify whether there is evidence worth pursuing, although interpretation depends on the disease setting, assessment schedule, and criteria. For hematologic tumors, the record says that other appropriate hematological response criteria may apply but does not specify which criteria were used.

The record refers to RECIST 1.1 for the solid-tumor clinical benefit assessment and separately describes RECIST v1.0 for target lesions assessed by MRI. It defines complete response as disappearance of all target lesions and partial response as a decrease of at least 30% in the sum of the longest diameters of target lesions. It defines overall response as complete response plus partial response. Since the record does not explain how the two RECIST references relate, it is not possible to resolve that point from the registry entry alone.

How should a confidence interval be understood?

In general, a confidence interval expresses the uncertainty around an estimate under the statistical model and procedure used. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. The primary endpoint entry does not report a confidence interval or describe the interval method. Secondary outcome titles mention Kaplan-Meier estimates with 95% CI for progression-free survival and survival rates, but the record does not provide those estimates or intervals. The presence of an interval in an outcome title is not itself a result.

For a single-group study, a confidence interval around a clinical benefit proportion would describe uncertainty about the observed proportion under the chosen method. It would not create a comparison with an untreated or alternative-treatment group. In general, inferential precision and causal interpretation are distinct: a precise estimate of an observed single-group outcome would not by itself resolve what would have happened under another treatment.

What do the secondary time-to-event outcomes involve?

Progression-free survival and overall survival are listed among the secondary outcomes. In general, time-to-event methods account for the time until an event and can retain information from participants whose event has not been observed by the end of follow-up, through censoring. Kaplan-Meier estimates are a standard way to describe event-free or survival probabilities over time. Their interpretation depends on event definitions, follow-up, censoring rules, and the population analyzed. Those details and the actual estimates are not reported in the registry record. Duration of response is also listed, including a measure concerning participants with a 99 day minimum duration of response, but no results are given.

The record lists zero analyses. It does not describe a statistical analysis plan, the statistical method for the primary endpoint, hypothesis tests, covariate adjustment, or interim analyses. A signal-seeking objective does not, on its own, establish a particular testing framework. The significance level and methods used for the posted efficacy results are not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than expected under a statistical model. It matters for count or rate analyses because a model that assumes too little variability can produce uncertainty estimates that are too small. This is a general statistical consideration, not a reported feature or method of this study. The primary endpoint is described as a participant count, and the registry record does not report a count model or an over-dispersion assessment.

The listed sample-size assumptions describe a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Time-to-event entries are described as total event counts, while other entries are participants per arm. These are planning illustrations, not observed power and not evidence that the trial itself used those assumptions. They also do not change the single-group design described in the registry record. The study's own sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists several secondary outcomes alongside the primary clinical benefit rate endpoint: overall response, progression-free survival, overall survival, Kaplan-Meier estimates of progression-free survival and survival rates, and duration of response. When multiple outcomes are considered, multiplicity can arise if many statistical tests or estimates are interpreted as separate evidence. In general, prespecifying a primary endpoint and controlling or otherwise addressing multiplicity can help clarify interpretation. The statistical plan, multiplicity strategy, and any hierarchy among outcomes are not reported in the registry record. The record lists zero analyses, so it does not provide test results from which a multiplicity approach could be assessed.

The Full Analysis Set is defined as all enrolled patients who received at least 1 dose of study drug and is identified as the primary set for efficacy analyses. The solid-tumor clinical benefit description excludes 3 TIO and 1 Lymphoma patients, leaving 80 for that assessment. The record does not report the observed size of the Full Analysis Set, a participant disposition by analysis population, or whether other populations were used for particular outcomes.

Missing-data handling is not described. The registry record does not say how participants without an assessment at 16 weeks were treated in the primary endpoint analysis, whether assessments were incomplete, or how censoring was handled for time-to-event outcomes. In general, missing outcome information can affect both the denominator and the interpretation of an estimate; the direction and extent depend on why information is missing and the analysis approach. No missing-data assumptions or sensitivity analyses are reported in the registry record.

The record also does not report a protocol-level statistical analysis plan, interim analyses, or a sample-size justification. These omissions limit assessment of whether the analyses followed prespecified rules and how robust the findings would be to alternative assumptions. Because no primary endpoint estimate is reported, missing-data and multiplicity methods cannot be evaluated against an observed efficacy result.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (4.8%), dyspnoea (4.8%), anaemia (3.6%), nausea (3.6%), urinary tract infection (3.6%).

The BGJ398 safety summary lists 83 participants at risk for serious adverse events and 33 affected. Its other adverse-event summary lists 83 participants at risk and 81 affected. The record also lists 11 deaths. These are descriptive counts; the record does not give enough detail in these figures to establish timing, duration of exposure, or whether events were considered related to treatment.

The most frequently listed serious adverse-event terms are sepsis and dyspnoea, each at 4.8%; anaemia and nausea, each at 3.6%; urinary tract infection at 3.6%; and abdominal pain at 2.4%. These percentages are reported as listed in the registry record. They should be read as event summaries, not as estimates of comparative risk. Because the study is single group and has no listed comparator, the figures do not show how event frequency compares with another treatment or with no study treatment.

In general, adverse-event counts describe what was recorded among participants under observation; they do not by themselves establish causation. A complete safety interpretation would depend on definitions, collection periods, participant exposure, event severity and relatedness, and handling of repeated events. Those details are not reported in the registry record. The figures also should not be treated as a complete account of every possible safety outcome.

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

The registry record identifies a phase II signal-seeking study of BGJ398 and defines its primary efficacy question as clinical benefit at 16 weeks. It gives the dose schedule and describes the response categories used for the solid-tumor assessment. It also identifies an analysis population definition and notes that the solid-tumor endpoint excludes 3 TIO and 1 Lymphoma patients. These details help establish what the study intended to assess and which stated population the endpoint description concerns.

However, the registry record does not report the primary clinical benefit result. It therefore cannot establish from the posted record how many participants achieved clinical benefit, how common that outcome was, or how precisely it was estimated. Secondary efficacy outcomes are listed but their results are not reported either. No conclusion about the magnitude of an observed efficacy signal can be drawn from endpoint definitions alone.

Even if a response or disease-stability result were available, the single-group design would constrain its interpretation. In general, a single-group result describes outcomes observed among treated participants; without a control group, it does not estimate a comparative treatment effect. The record does not provide a randomized comparison or a counterfactual estimate. The stated signal-seeking purpose is to inform whether further study may be warranted, not to establish a controlled treatment contrast.

The safety summaries report counts of affected participants, deaths, and selected serious adverse-event terms. They do not establish that treatment caused those events, and they do not provide a comparative safety estimate. The reason the study was terminated is not reported in the registry record, so the status alone should not be taken to imply a particular efficacy or safety finding.

Overall, the record supports a description of the study design, treatment schedule, endpoint definitions, and selected safety summaries. It does not provide the efficacy results or analysis detail needed to judge the primary endpoint, quantify uncertainty, assess missing data, or evaluate the statistical plan. Those are substantive limits on what can be concluded from this registry record.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a study question and a reported result. The registry record defines a clinically interpretable endpoint—clinical benefit at 16 weeks—and specifies the categories included for solid tumors. Yet without the endpoint count, rate, or an uncertainty interval, the posted record does not permit a quantitative assessment of the primary finding. A clearly stated endpoint cannot substitute for its observed result.

The single-group, signal-seeking design also highlights the difference between estimating an outcome in a treated group and estimating a treatment effect. In general, a single-group study can describe what happened among enrolled participants, but it lacks a concurrent control for distinguishing treatment-associated outcomes from other influences. That distinction should remain central when interpreting a reported signal, even when the signal is potentially useful for deciding whether further study is warranted.

The population description matters as well. Enrollment was 84, whereas the solid-tumor clinical benefit description states that 3 TIO and 1 Lymphoma patients were excluded, leaving 80 patients for that assessment. The Full Analysis Set has a separate definition based on receiving at least 1 dose. Clear denominators and participant disposition are important for understanding which population an estimate represents; the registry record does not provide the complete disposition or the primary endpoint result.

Finally, the record lists several secondary outcomes and safety summaries without reporting efficacy analyses or the statistical plan. This makes it difficult to assess precision, missing-data handling, multiplicity, or the relationship between planned and reported analyses. The statistical importance of the record is therefore as much about what cannot be evaluated as what it specifies: endpoint definitions and design features are present, while the results and key analysis details are not reported in the registry 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.

The principal trial-specific limitation in the registry record is the absence of the primary clinical benefit result. The endpoint is named and defined, but no count, proportion, or interval is reported. Secondary efficacy outcomes are listed without outcome estimates. As a result, the efficacy question cannot be answered quantitatively from this record.

The design is single group, with allocation recorded as NA and no masking. No comparator is listed, so the study cannot provide a like-for-like control comparison. The record's signal-seeking objective is relevant context, but does not remove the limitations of interpreting outcomes without a control group.

The participant populations require careful distinction. Enrollment was 84, while the solid-tumor clinical benefit description excludes 3 TIO and 1 Lymphoma patients and states a population of 80. The Full Analysis Set is defined as enrolled patients who received at least 1 dose, but its observed size and participant flow are not reported. The relationship between the RECIST 1.1 reference for clinical benefit and the separate RECIST v1.0 description is also not explained. Response criteria for hematologic tumors are not specified beyond noting that appropriate hematological criteria may apply.

The registry record does not report the statistical analysis plan, sample-size justification, missing-data approach, multiplicity strategy, or interim analyses. It also does not give the reason for termination. The safety information is limited to listed counts and selected serious-event terms and does not establish causation or provide a control comparison. These omissions restrict evaluation of the study's results and their precision, even apart from the missing primary efficacy estimate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: BGJ398 for Patients With Tumors With FGFR Genetic Alterations — NCT02160041.
• Registry record last updated 2019-06-18; status last verified 2019-05.
• Results first posted 2019-06-18.
• 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.

18. Record Summary

NCT02160041 is a phase II, single-group study of BGJ398 for patients with tumors with FGFR genetic alterations, sponsored by Novartis Pharmaceuticals. Enrollment was 84; the study started on 2014-07-24, had a primary completion date of 2018-04-30, and is listed as terminated. The treatment schedule was 125 mg once daily for the first 21 days of a 28-day cycle.

The primary endpoint was clinical benefit rate at 16 weeks. For solid tumors, the record defines clinical benefit as complete response, partial response, or stable disease and states that 3 TIO and 1 Lymphoma patients were excluded, leaving 80 patients for that assessment. The Full Analysis Set included enrolled patients who received at least 1 dose. The primary endpoint result and secondary efficacy estimates are not reported in the registry record.

The safety summaries list 83 participants at risk and 33 affected for serious adverse events, 83 at risk and 81 affected in the other adverse-event summary, and 11 deaths. The study has no listed comparator, and the reason for termination is not reported in the registry record.