Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101) (NCT02393248), a non-randomized phase 1, phase 2 study. The primary outcome is Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE).

2. Clinical Question

This is primarily a safety and dose-development question, rather than a randomized test of whether pemigatinib improves an outcome compared with another treatment. The registry record describes dose escalation, dose expansion, and combination therapy, but does not report a single common treatment schedule across all participants. Pemigatinib was given intermittently or continuously in different groups, at varying doses, and alongside different drugs in Part 3.

That structure matters when reading the posted results. Participants in different groups may have received different regimens and entered different parts of the study. The record does not establish that groups were exchangeable or intended to serve as controls for one another. It therefore does not support a direct causal comparison of adverse-event counts or other outcomes between regimens. The result of the primary endpoint itself is not reported in the registry record information; the group-level safety figures should not be mistaken for an overall primary-endpoint estimate.

3. Trial Design

This was a Phase 1/2, open-label, nonrandomized, sequential study of pemigatinib in subjects with advanced malignancies. The registry describes three parts: dose escalation, dose expansion, and combination therapy. Its stated purpose was to evaluate safety, tolerability, and pharmacological activity. The record lists an enrollment of 201 and identifies Incyte Corporation as sponsor. The study status is terminated; the recorded start date is 2015-02-27 and the primary completion date is 2021-12-17.

In Parts 1 and 2, pemigatinib was administered alone in intermittent or continuous schedules. Intermittent schedules generally describe treatment on Days 1 through 14 followed by a treatment break on Days 15 through 21; continuous schedules describe dosing on Days 1 through 21 of a 21-day cycle. The listed dose levels and frequencies vary by group. Part 3 includes regimens combining pemigatinib with other drugs, including gemcitabine and cisplatin, trastuzumab, docetaxel, pembrolizumab, or retifanlimab. Some Part 3 arm descriptions are incomplete in the registry record, so their full administration details are not reported in the registry record.

No masking was used. The nonrandomized allocation and sequential model mean that treatment assignment was not described as random, and no common control group is listed. The arm groups differ in dose, schedule, study part, or combination treatment. As a result, differences between groups can reflect those design and participant differences as well as any treatment-related variation. The registry record does not report the rationale for the sequence of groups or a statistical plan that would make between-group comparisons interpretable as controlled treatment effects.

The primary endpoint covers Parts 1 and 2 combined and concerns treatment-emergent adverse events. Other listed outcomes include overall response rate in Parts 2 and 3 and pharmacokinetic measures in Parts 1 and 2. The existence of those outcome listings does not by itself establish that results are reported for them.

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.

Only the first 6 of 25 groups are shown.

Part 1: Monotherapy Dose Escalation

Reasons for not completing this period:

Part 2: Monotherapy Dose Expansion

Reasons for not completing this period:

Part 3: Combination Therapy

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population: all enrolled 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.

Only the first 6 of 26 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), measured over up to 763 days.

The primary endpoint is the number of participants in Parts 1 and 2 combined with any treatment-emergent adverse event, measured in participants. The record defines adverse events broadly as new or worsening undesirable signs, symptoms, or medical conditions occurring after informed consent. Abnormal laboratory or test results count as adverse events only when they cause clinical signs or symptoms, are considered clinically meaningful, require therapy, or require a change in study drug.

A treatment-emergent adverse event is defined by timing: an event reported for the first time, or a pre-existing event that worsens, after the first study-drug dose and within 30 days of the last dose. The stated timeframe for this endpoint is up to 763 days. The safety population consists of all enrolled participants who received at least one dose of study drug.

Counting participants with any such event is a way to describe how many people experienced at least one event during the defined observation period. It is useful in early-phase research because safety and tolerability are central study aims, and the measure can include a broad range of clinical events rather than only a selected diagnosis. However, a participant count does not convey the number of events per person, duration, severity, seriousness, or whether an event was judged related to study treatment. Those details require separate results and definitions. The overall primary-endpoint count is not reported in the registry record information, so the endpoint definition should not be read as an observed result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

A participant count records how many people met a specified outcome definition. For this primary endpoint, the specified event is at least one treatment-emergent adverse event within the defined timing window. It is not the same as counting every adverse-event episode: a participant with multiple events may still contribute once to a measure of participants with any event. The endpoint description does not provide an overall count or an overall denominator in the registry record information.

Counts need a denominator to provide context. A count of affected participants can be read alongside the number at risk for that particular group and outcome. It should not be confused with the total enrollment or automatically transferred to a different population. In this study, the stated safety population includes enrolled participants who received at least one dose, while the posted safety group summaries give their own at-risk counts. The number analyzed for the primary endpoint is not reported in the registry record information.

Why is the study structure important?

Random allocation can help balance known and unknown participant characteristics between treatment groups. This study is listed as nonrandomized, open-label, and sequential, and the registry cautions that its arms are not a like-for-like control comparison. In general, sequential dose-development groups can differ in more than dose: they can vary by schedule, study part, combination partner, or participant characteristics. Therefore, simple differences in group counts do not isolate a treatment effect.

Open-label means treatment masking was not used. This can affect how symptoms are reported, assessed, or managed, although the extent of any effect cannot be determined from the registry information. These design features do not invalidate descriptive safety reporting; they define what the reporting can support. A descriptive account can characterize observed events within groups, while a causal comparison requires a design and analysis that address confounding and group comparability.

How should serious and other event summaries be read?

The registry separates serious adverse events, other adverse events, and deaths in its group listings. Seriousness is a distinct classification from severity: a serious adverse event is categorized by regulatory seriousness criteria, whereas severity describes intensity. These concepts are not interchangeable. The information summarized does not provide a full event-level account, severity grades, relatedness judgments, or reasons for death. Such details should not be inferred from the counts.

The listed serious-event terms include acute kidney injury, constipation, febrile neutropenia, anaemia, fatigue, and pneumonia, with percentages shown in the record. Because the corresponding denominators and percentage calculation are not reported in the registry record information, those percentages should be read only as registry-listed values, not as comparable risks across treatment groups. Where counts are sparse, even a small change in the number of affected participants can change the apparent pattern substantially.

What can planning calculations tell readers?

In general, a sample-size calculation estimates how much information a planned study might need for a specified statistical objective. It is a planning illustration, not an observed result or a measure of the study's actual power. The registry-based planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They define the effect to detect as a stated fraction of an observed effect. For time-to-event outcomes, the planning approach is described as using the total number of events with the Schoenfeld method; other outcomes are described in participants per arm.

Those assumptions do not establish that the trial itself used those methods. The record information does not report the trial's sample-size justification or a plan for inferential testing. In addition, the study arms are nonrandomized and not like-for-like controls, so planning illustrations based on an observed effect should not be mistaken for evidence that the study can estimate a controlled treatment difference. Any displayed sample-size values are planning quantities rather than observed participants or observed power.

What inferential details are missing?

A confidence interval, in general, expresses the precision of an estimated quantity under a specified statistical model. A narrow interval indicates greater precision than a wide interval, while neither alone resolves bias from a nonrandomized design. The registry information does not report confidence intervals for the safety counts, a comparative model, hypothesis tests, or an adjustment strategy for multiple outcomes. It also does not report interim-analysis procedures or detailed stopping rules.

Without those details, interpretation should remain descriptive. The available record identifies endpoint definitions, groups, and selected safety counts, but does not supply a complete inferential analysis for judging differences between regimens. No unreported test, adjustment, or model should be assumed.

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("Part 1: Intermittent Pemigatinib 1/2/4 mg QD", "Part 1: Intermittent Pemigatinib 6 mg QD", "Parts 1 and 2: Intermittent Pemigatinib 9 mg QD", "Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD", "Part 1: Intermittent Pemigatinib 20 mg QD", "Parts 1 and 2: Continuous Pemigatinib 9 mg QD")
n      <- c(3, 4, 7, 50, 6, 14)
events <- c(3, 3, 7, 50, 6, 14)
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  Part 1: Intermittent Pemigatinib 1/2/4 mg QD  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Part 1: Intermittent Pemigatinib 6 mg QD  4  3  75.0  19.4  99.4  30.1  95.4  28.4  94.7
ARM  Parts 1 and 2: Intermittent Pemigatinib 9 mg QD  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD  50  50  100.0  92.9  100.0  92.9  100.0  93.0  100.0
ARM  Part 1: Intermittent Pemigatinib 20 mg QD  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Parts 1 and 2: Continuous Pemigatinib 9 mg QD  14  14  100.0  76.8  100.0  78.5  100.0  78.2  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists numerous outcomes, including the primary adverse-event measure, overall response rate in Parts 2 and 3, and several pharmacokinetic measures in Parts 1 and 2. When a study evaluates multiple outcomes or analyses, there is a general risk that some apparent findings may occur by chance if many statistical tests are conducted. Methods such as prespecifying a primary comparison or adjusting for multiple testing can address that issue, but the registry record information does not report a multiplicity strategy. The number of listed outcome measures and analyses does not by itself establish how many were tested or how results were interpreted.

Missing-data procedures are also not reported in the registry record. The endpoint definition states an observation timeframe and defines the safety population, but does not explain how incomplete follow-up, missing event information, or withdrawal from treatment was handled for analysis. The number of participants with missing endpoint data is not reported in the registry record information. It would be inappropriate to assume that missing observations were absent, ignored, imputed, or handled by a particular method.

The safety population is defined as enrolled participants who received at least one dose of study drug. The number in that population and the number analyzed for each outcome are not reported in the registry record information. No intention-to-treat population or other efficacy analysis population is defined in the information summarized. These omissions limit the ability to assess whether different outcomes used consistent denominators or whether exclusions could affect interpretation.

The registry record information also does not report a complete statistical analysis plan, interim analyses, or a sample-size justification. These absences matter because they prevent readers from distinguishing planned analyses from exploratory ones and from assessing how missingness or multiple testing may have influenced conclusions.

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: acute kidney injury (100.0%), constipation (100.0%), febrile neutropenia (100.0%), anaemia (50.0%), fatigue (50.0%).

The serious adverse-event listings give, by group, the number at risk and the number affected; the other adverse-event listings and deaths are also presented as group counts. For example, the Parts 1 and 2 intermittent pemigatinib 13.5 mg group lists 21 participants affected by serious adverse events among 50 at risk, 50 affected by other adverse events among 50 at risk, and 37 deaths. These are observed group summaries and should not be interpreted as treatment comparisons.

Group sizes, schedules, study parts, and combination treatments vary. The groups were not randomized against one another, so a higher or lower count cannot establish that a regimen caused the difference. Deaths are recorded as counts, but cause and relationship to treatment are not reported in the registry record information. The serious-event term percentages are also listed without the denominators or calculation details needed to compare them reliably. Seriousness should not be confused with severity, and the posted counts do not describe event duration or recurrence.

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

The record establishes that this was a nonrandomized, open-label Phase 1/2 study with sequential dose-escalation, dose-expansion, and combination-therapy parts. It also gives definitions for the primary safety endpoint and describes the safety population. The posted safety summaries document adverse events and deaths across groups with differing regimens. Those findings are descriptive evidence about what was recorded in those groups.

They do not establish a causal effect of pemigatinib, a combination partner, dose, or schedule. There is no randomized control group, and the registry explicitly says the arms are not a like-for-like control comparison. The counts cannot by themselves show whether any regimen increased or decreased risk relative to another treatment or to no treatment. Nor do they establish that a listed event was caused by a study drug. Attribution and event-level context are not reported in the registry information.

The primary endpoint is a participant count for any treatment-emergent adverse event in Parts 1 and 2 combined, but the overall result for that endpoint is not reported in the registry record information. Group-level serious and other adverse-event counts are not substitutes for that combined primary endpoint. The available information also does not provide a complete account of response or pharmacokinetic results, even though those outcomes are listed.

Finally, the record's terminated status does not explain why the study ended. Without the reason for termination, a full analysis plan, outcome-specific denominators, and fuller results, the status should not be treated as evidence of a particular safety or efficacy conclusion. The appropriate reading is limited to the design and results that are actually recorded.

14. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between dose-development evidence and controlled comparative evidence. A sequential, nonrandomized study can describe safety across multiple dosing schedules and combinations, while its changing regimens complicate direct comparisons. The registry's caution that arms are not like-for-like controls is central to interpretation, not a minor technical qualification.

The study also demonstrates why endpoint definitions and analysis populations matter. The primary outcome concerns participants with any treatment-emergent adverse event, with timing anchored to the first and last doses. The safety population is based on receipt of at least one dose. Those definitions explain what an eventual estimate would represent, but the primary-endpoint result and its analysis denominator are not reported in the registry information.

Another statistical lesson is that event counts, percentages, and deaths answer different questions. Counts describe observed participants; percentages require clear denominators; and serious-event status does not convey severity or treatment relatedness. Small, heterogeneous groups make simple rankings especially fragile. A planning calculation, even when based on a stated effect and significance level, is not observed power and does not correct for the lack of a randomized comparison.

For clinical researchers, the record underscores the value of complete reporting: outcome-specific denominators, missing-data methods, multiplicity procedures, analysis populations, and reasons for termination all shape how results can be interpreted. Their absence does not erase the descriptive data, but it limits the strength and scope of conclusions that can be drawn from them.

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 principal limitation is the nonrandomized sequential design. Study groups varied by dose, schedule, part, and combination treatment, and the registry explicitly states that arms are not a like-for-like control comparison. Group-level differences therefore cannot be interpreted as randomized treatment effects. The open-label design also means treatment masking was absent; how that may have affected reporting or assessment is not established in the registry record.

The registry information does not report the overall primary-endpoint result, its analysis denominator, or a complete account of outcome-specific analysis populations. It does not describe missing-data handling, multiplicity procedures, confidence intervals, or a full statistical analysis plan. The reason for termination is not reported in the registry record. These gaps restrict assessment of precision, completeness, and the intended role of individual analyses.

Safety summaries omit important context for interpretation, including event severity, relationship to study drug, event duration, causes of death, and detailed follow-up by group. The listed serious-event term percentages lack reported denominator and calculation details in the information. Some combination-arm descriptions are truncated, so the complete regimen details for those groups are not reported in the registry record.

Finally, the registry lists an enrollment of 201, but that figure does not establish how many participants received study drug or contributed to each endpoint. It should not be substituted for the denominator of any particular safety result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101) — NCT02393248.
• Registry record last updated 2023-01-06; status last verified 2022-12.
• Results first posted 2023-01-06.
• 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

NCT02393248 is an open-label, nonrandomized Phase 1/2 sequential study of pemigatinib in advanced malignancies. The record describes dose escalation, dose expansion, and combination therapy, with intermittent and continuous schedules and multiple combination drugs. The listed enrollment is 201; the study is terminated. Its recorded start date is 2015-02-27 and primary completion date is 2021-12-17.

The primary endpoint is the number of participants in Parts 1 and 2 combined with any treatment-emergent adverse event, in a safety population defined by receipt of at least one dose. Group-level safety counts are listed, but the overall primary-endpoint result and its analysis denominator are not reported in the registry information. Because the arms were not randomized and are not like-for-like controls, the group summaries are descriptive rather than controlled comparisons.