An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer (NCT02365597), a na phase 2 study. The primary outcome is Main Study: Percentage of Participants With Best (Overall) Objective Response.

2. Clinical Question

In general, an objective response endpoint asks whether measurable disease met prespecified response criteria. It is distinct from endpoints that describe how long a response lasts, how long participants remain alive without progression, or overall survival. Those outcomes are listed as secondary outcomes in this study, but their results are not included in the registry information.

3. Trial Design

The registry identifies NCT02365597 as a phase 2, multicenter, open-label study sponsored by Janssen Research & Development, LLC. The study title describes two dose regimens of a pan-FGFR tyrosine kinase inhibitor in participants with metastatic or surgically unresectable urothelial cancer with FGFR genomic alterations. The recorded enrollment is 239. The study began on 2015-04-22, and its primary completion date is recorded as 2022-09-15. Its status is active, not recruiting.

The design is classified as single group, with allocation recorded as not applicable and masking recorded as none. These features matter when interpreting the regimen descriptions: the record does not describe random assignment to dose groups, and it does not establish a randomized comparison between regimens. It reports that two regimens were used before interim analysis 1, after which Regimen 1 was closed to further enrollment and the starting dose of Regimen 2 was increased. Thus the dosing approach changed during the study.

The record also lists a drug-drug interaction sub-study involving midazolam, metformin, and erdafitinib. Its safety listing is separate from the main-study regimen listings and should not be read as a control arm. The registry lists 19 outcome measures and no analyses. The outcome list includes best overall objective response as the primary measure, with progression-free survival, duration of response, overall survival, treatment-emergent adverse events, and erdafitinib plasma concentrations among the secondary outcomes.

Open-label describes the recorded masking status; it does not by itself establish how response assessments were conducted or whether assessors were independent. Those details, as well as the full allocation procedures and any planned statistical analysis, 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The population included participants who received at least 1 dose of study drug.

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: Safety analysis set included participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Main Study: Percentage of Participants With Best (Overall) Objective Response, measured over From Cycle 1 Day 1 up to 6 years 2 months.

The primary endpoint is the percentage of participants with best overall objective response. Responders are defined as participants whose best overall response was complete response or partial response. The response categories are ordered in the registry description as complete response, partial response, stable disease, and progressive disease. Complete and partial responses were confirmed according to RECIST version 1.1.

Under that definition, complete response requires disappearance of all target lesions; any pathological lymph nodes, whether target or non-target, must have a short axis < 10 millimeters. Partial response requires at least a 30 percent decrease in the sum of target-lesion diameters, using the baseline sum as the reference. The endpoint timeframe is from Cycle 1 Day 1 up to 6 years 2 months. The endpoint population includes participants who received at least 1 dose of study drug.

In general, response rates are useful because they express the share of a defined population meeting a clinically specified tumor-response criterion. They provide a direct summary of response occurrence but do not, by themselves, describe how long responses last or establish a treatment effect relative to a control. Duration of response is listed separately as a secondary outcome. The primary response percentage and its uncertainty are not reported in the registry record, so the endpoint definition can be described but its observed result cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a response percentage represent?

For a binary endpoint, each participant is classified according to whether the endpoint occurred. For this study, the registry defines response as a best overall response of complete response or partial response. In general, a response percentage is the number classified as responders relative to the endpoint’s analysis population, expressed as a percentage. Interpreting it requires knowing both the responder count and the denominator, along with the rules used to assess response. The endpoint description identifies the population as participants who received at least 1 dose, but the registry record does not report the primary response count or percentage.

Best overall response is a participant-level summary across the study’s response assessments: the endpoint uses the best category achieved, according to the specified ordering of response categories. This differs from using a single assessment at a fixed visit. The registry gives the endpoint timeframe as from Cycle 1 Day 1 up to 6 years 2 months. The record describes confirmation of complete and partial responses under RECIST version 1.1. It does not provide additional details about assessment schedules, independent review, or handling of assessments that could not be evaluated.

Why do the response criteria matter?

Response criteria make the outcome more reproducible by specifying what counts as a response. The registry defines complete response as disappearance of all target lesions, with any pathological lymph nodes reduced to a short axis < 10 millimeters. Partial response is defined as at least a 30 percent decrease in the sum of target-lesion diameters relative to baseline. A participant with stable disease or progressive disease is not a responder under the stated CR-or-PR definition. In general, standardized criteria help distinguish response categories, but the criteria do not remove uncertainty from measurement or from the observed estimate.

For a binary response percentage, statistical uncertainty depends in part on the number of participants contributing to the endpoint and the number meeting the response definition. A confidence interval is a way to express that uncertainty around an estimate. It does not guarantee that the true value lies within a particular interval; rather, it reflects the performance of a statistical procedure over repeated use under its assumptions. No interval or primary response estimate is reported in the registry record, so the precision of this endpoint cannot be assessed from the record.

What can a comparison establish?

In general, a randomized comparison helps balance measured and unmeasured prognostic factors across assigned groups, supporting a causal interpretation of differences under appropriate conduct and analysis. This study is recorded as single group, with allocation not applicable. The registry specifically cautions that the listed arms are not a like-for-like control comparison. Thus, a numerical contrast between groups would not, on its own, identify the effect of one regimen versus another.

The treatment regimen changed after interim analysis 1: Regimen 1 closed to further enrollment and the starting dose of Regimen 2 increased. This sequence is important because participants treated under different regimens may have entered at different points in the study or under different circumstances. The record does not report enough detail to assess how such factors were handled analytically. The drug-drug interaction sub-study also involves midazolam and metformin alongside erdafitinib; it serves a different stated context from the main-study regimen listings and should not be treated as a control group.

How should the planning illustration be read?

In general, a sample-size calculation asks how many observations a planned study might need to detect a specified effect under chosen assumptions. The registry’s planning illustration is based on the observed effect, assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, and considers an effect equal to a stated fraction of the observed effect. The record says that non-time-to-event illustrations give participants per arm, while time-to-event illustrations give a total number of events. These are planning illustrations, not observed power and not a report of the trial’s original design justification.

Observed power is not a substitute for an estimate and its uncertainty. In general, once data have been collected, the observed estimate and confidence interval are more informative about what the data support than a power calculation based on the observed effect. The record does not report the study’s own sample-size justification, and no planning value should be treated as a clinical result.

Which analysis details are unavailable?

The registry lists 19 outcome measures and no analyses. The statistical analysis plan, the method used to estimate the primary response percentage, any confidence-interval method, and any hypothesis-testing procedure are not reported in the registry record. The record also does not report how missing or unevaluable response assessments were handled, whether analyses were prespecified at interim analysis 1, or how the study addressed multiple outcomes. These omissions limit independent appraisal of the numerical results, beyond the fact that the primary endpoint result itself is not reported in the registry record.

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("Main Study: Regimen 1: Erdafitinib 10 Milligrams (", "Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg", "Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg")
n      <- c(33, 78, 101)
events <- c(7, 27, 40)
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  Main Study: Regimen 1: Erdafitinib 10 Milligrams (  33  7  21.2  9.0  38.9  10.7  37.8  10.7  37.9
ARM  Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg  78  27  34.6  24.2  46.2  25.0  45.7  25.0  45.7
ARM  Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg  101  40  39.6  30.0  49.8  30.6  49.4  30.6  49.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including the primary best overall objective response endpoint and secondary outcomes covering progression-free survival, duration of response, overall survival, treatment-emergent adverse events, and erdafitinib plasma concentrations. It records no analyses. A statistical plan specifying how the primary and secondary outcomes were tested, or how multiplicity was addressed, is not reported in the registry record.

In general, testing many outcomes can increase the chance of obtaining at least one apparently notable result by chance if each is assessed using a separate significance test. Methods for controlling multiplicity can define how evidence is interpreted across outcomes. The registry information does not establish whether such methods were planned or used; no approach should be inferred from the number of outcomes listed.

Missing-data handling is also not reported in the registry record. In general, missing response assessments can affect a response percentage if participants without an evaluable assessment are treated differently from those with observed assessments. The endpoint population is described as participants who received at least 1 dose of study drug, but that alone does not specify the denominator used for a reported analysis or the treatment of missing, unevaluable, or incomplete assessments. The primary response result is not reported, so the effect of any missing-data rule cannot be examined.

The registry does not report whether the primary analysis population was defined separately from the endpoint population, or how protocol deviations were handled. It also does not report an analysis plan for the changes in dose regimen or for the drug-drug interaction sub-study. These missing details prevent a full assessment of analysis populations and prespecified decision rules.

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: intestinal obstruction (8.0%), dyspnoea (6.1%), urinary tract infection (5.1%), ileus paralytic (4.0%), rectal haemorrhage (4.0%).

The safety listings give, for the main-study regimen groups, serious adverse event counts of 14 among 33 participants for Regimen 1, 39 among 78 for Regimen 2, and 47 among 101 for Regimen 3. The drug-drug interaction sub-study listing gives 9 among 25. These are group-specific counts; they should not be added together or treated as results from randomized comparison groups. The registry also lists deaths: 31, 62, 83, and 3, respectively. The counts alone do not establish cause or treatment attribution.

The most frequently listed serious adverse event terms are Intestinal Obstruction at 8.0%, Dyspnoea at 6.1%, Urinary Tract Infection at 5.1%, Ileus Paralytic at 4.0%, Rectal Haemorrhage at 4.0%, and Pyrexia at 4.0%. The record does not give further denominator or analysis details for these term percentages in the information.

In general, adverse-event counts and percentages describe what was recorded in the study population; they do not by themselves show that a drug caused an event. Differences between groups are especially difficult to interpret causally without random assignment and comparable follow-up. The changing regimens and separate sub-study should therefore remain in view when reading these listings.

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

The registry record establishes the study question and response definition, but it does not report the primary response estimate. Readers can identify the target population, the response categories, the RECIST version 1.1 criteria, and the endpoint timeframe, but cannot determine from this record what percentage met the responder definition or how precisely that percentage was estimated.

Even if response results are considered alongside the study’s safety listings, they answer different questions. Response is a tumor-response outcome defined by the best overall category during the study. The serious adverse event counts and listed terms describe safety events recorded in the group listings. Neither type of result, on its own, provides a randomized comparison with an alternative treatment or no treatment.

The record’s single-group classification, lack of masking, and absence of randomized allocation are central to interpretation. The dose regimen also changed following interim analysis 1, and Regimen 1 was closed to further enrollment. The record warns that the arms are not a like-for-like control comparison. Accordingly, any apparent differences across regimen groups would be descriptive unless supported by a suitable analysis and assumptions that are not reported.

In general, an observed response percentage can characterize outcomes among participants assessed under a study’s eligibility, treatment, and response-assessment rules. It does not, by itself, establish how outcomes would differ under another treatment, nor does a response category describe response duration or survival. Those outcomes are listed separately as secondary measures. Their results are not reported in the registry information.

The appropriate conclusion is bounded: the registry describes a phase 2 study of erdafitinib in a defined urothelial cancer population and specifies an objective response endpoint. The primary endpoint result, its uncertainty, and the statistical analysis details are not reported in the registry record. No conclusion about the magnitude or comparative effect of treatment can be drawn from those absent results.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a well-defined endpoint and an unavailable endpoint result. The registry gives operational response criteria, including the complete- and partial-response definitions under RECIST version 1.1, and identifies the endpoint population and timeframe. Yet it does not report the response percentage, count, or interval. A precise endpoint definition is necessary for interpretation, but cannot substitute for the estimate and its uncertainty.

The study also illustrates why design labels matter. A single-group study can describe outcomes among participants treated under its study conditions, but it does not provide the same basis for causal comparison as random assignment to comparable groups. Here, allocation is not applicable, masking is none, and the registry cautions that the listed arms are not a like-for-like control comparison. The regimen changes after interim analysis 1 add context to any descriptive group results.

Statistical planning figures should also be kept distinct from evidence about what occurred. The registry describes planning illustrations based on the observed effect, with specified assumptions. Such illustrations can help frame future planning, but they do not replace the observed response result, and they are not observed power. The record does not provide the study’s own sample-size justification or statistical analysis plan.

Finally, the outcome list spans response, time-to-event outcomes, safety, and drug concentration. In general, each outcome has its own estimand, data requirements, and interpretation. Without the analysis details and reported results, readers cannot assess how these outcomes were prioritized or how uncertainty and multiplicity were handled. The record’s value is therefore strongest as a description of the study design, endpoint definition, and selected safety counts, rather than as a complete statistical account of treatment effects.

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 does not report the primary best overall objective response result, its numerator and denominator, a confidence interval, or a p-value. The precision of the response estimate and the amount of observed response therefore cannot be assessed. It also does not report results for the listed secondary outcomes in the information.

The study is open-label and classified as single group, with allocation not applicable. It has no randomized control comparison identified in the record. Regimen 1 was closed to further enrollment after interim analysis 1, and the starting dose of Regimen 2 increased. These design features limit interpretation of between-regimen contrasts and make it inappropriate to treat listed groups as exchangeable control arms.

The registry does not report the statistical analysis plan, response-assessment schedule, analysis method, confidence-interval method, handling of missing or unevaluable assessments, or the approach to multiple outcomes. It does not provide further information on whether response assessments were independently reviewed. The record also does not state the study’s own sample-size justification or whether any interim-analysis procedures were prespecified.

The safety listings provide group counts and selected serious adverse event terms, but the information described does not establish event causality or support a randomized comparative safety conclusion. The drug-drug interaction sub-study includes midazolam and metformin with erdafitinib and should be read separately from the main-study regimens. Taken together, these limitations leave the registry record insufficient for estimating comparative treatment effects or evaluating the precision of the primary endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer — NCT02365597.
• Registry record last updated 2026-09-25; status last verified 2026-09.
• Results first posted 2023-10-10.
• 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

NCT02365597 is a phase 2, multicenter, open-label study sponsored by Janssen Research & Development, LLC, of erdafitinib in participants with metastatic or surgically unresectable urothelial cancer with FGFR genomic alterations. The registry records enrollment of 239, a start date of 2015-04-22, primary completion on 2022-09-15, and status active, not recruiting.

The primary outcome is the percentage of participants with best overall objective response, defined as complete or partial response under RECIST version 1.1, among participants who received at least 1 dose. The record describes changes to the dose regimens after interim analysis 1 and identifies a separate drug-drug interaction sub-study. It classifies the design as single group and cautions that the arms are not a like-for-like control comparison.

The primary endpoint result and statistical analysis details are not reported in the registry record. Safety counts and selected serious adverse event terms are listed, but they do not establish causality or comparative treatment effects.