Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Relapsed or Refractory Advanced Non-Small Cell Lung Cancer With an FGFR Alteration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Relapsed or Refractory Advanced Non-Small Cell Lung Cancer With an FGFR Alteration (NCT05253807), a non-randomized phase 2 study. The primary outcome is Objective Response Rate (ORR) in Cohort A.

2. Clinical Question

The clinical question is therefore descriptive rather than comparative: among the eligible participants treated in the squamous cohort, how many met the specified tumor-response criteria during the stated assessment period? The study also listed ORR in Cohort B and time-to-event outcomes for Cohort A among its secondary outcomes, along with safety outcomes. Because treatment assignment was not randomized and no comparator arm was included, differences between participants or between cohorts cannot be interpreted as treatment effects relative to a control. Cohort A and Cohort B represent different NSCLC histologies, not like-for-like treatment groups.

3. Trial Design

NCT05253807 is recorded as a completed Phase 2 study sponsored by Incyte Corporation. Its official title describes an open-label, single-arm, multicenter study of pemigatinib in participants with advanced NSCLC and an FGFR alteration who progressed on previous therapy. The registry lists enrollment of 8 participants. The recorded study start was 2022-04-29, and primary completion was 2023-08-16.

The two cohorts were defined by histology. Cohort A included participants with squamous NSCLC and known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements. Cohort B included participants with nonsquamous NSCLC and the corresponding alteration description. Participants in both cohorts were to receive intermittent dosing of pemigatinib. Further details of the dosing schedule are not reported in the registry record.

The study was open-label, with no masking, and nonrandomized. The parallel model designation does not make the cohorts randomized controls: the cohorts differ by histology, and each received the study drug. As a result, neither cohort supplies a concurrent untreated or active-comparator estimate. The registry does not report a comparator, allocation sequence, or blinding procedure beyond the recorded absence of masking.

The primary outcome was ORR in Cohort A, assessed up to 267 days. The registry lists ORR in Cohort B, progression-free survival, duration of response, and overall survival in Cohort A as secondary outcomes, together with adverse-event outcomes. Although the study status is completed, outcome estimates and analysis details for these measures are not reported in the registry record. Completion status alone does not establish what the measured results were.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: This study was conducted at 8 study centers in Spain, Italy, France, and the United States.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Population: all enrolled participants who received at least 1 dose of pemigatinib. The confidence interval was calculated based on the exact method for binomial distribution.

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 Objective Response Rate (ORR) in Cohort A, measured over up to 267 days.

The primary endpoint, ORR in Cohort A, is the percentage of participants with squamous NSCLC who had a complete response (CR) or partial response (PR). The registry defines response using RECIST v1.1 and says that an independent central radiology review determined response. The assessment timeframe was up to 267 days.

Under the stated definition, CR requires disappearance of all target and non-target lesions and no new lesions. Pathological lymph nodes, whether target or non-target, must have a short-axis measurement <10 millimeters (mm). PR requires complete disappearance or at least a 30% decrease in the sum of target-lesion diameters relative to baseline, no new lesions, and no progression of non-target lesions.

ORR is used as a summary of the proportion meeting a prespecified tumor-response definition. General statistical context: a proportion can be readily understood, but its precision depends on the number of participants evaluated and the number meeting the definition. A confidence interval communicates uncertainty around that estimate; it does not make the result a comparison with another treatment. The registry states that an exact binomial method was used for the confidence interval and defines the full analysis population as all enrolled participants who received at least 1 dose of pemigatinib. However, the observed ORR, the interval limits, and the number included in this primary analysis are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a percentage of participants and specifies a 95% confidence interval. It also states that the interval was calculated using the exact method for the binomial distribution. The numerical estimate and interval are not reported in the registry record, so the method can be explained but the precision of this study's ORR cannot be evaluated from the recorded results.

What does a proportion estimate?

General statistical explanation: a proportion represents the number of participants meeting a defined condition relative to the number evaluated. Here, the condition is achieving CR or PR under RECIST v1.1, as determined by independent central radiology review. The population definition is all enrolled participants who received at least 1 dose of pemigatinib. The registry does not state the number included in the primary endpoint analysis or provide the response count. Enrollment of 8 is the total study enrollment, but that figure alone does not establish the endpoint denominator.

In a small study, a single participant's classification can materially affect a proportion. A confidence interval expresses the uncertainty expected around an estimate, given the available observations and the statistical model. General statistical explanation: an interval is not a range of possible treatment effects, and it does not account for all sources of uncertainty, such as selection into a single-arm study or differences from another population. The stated exact binomial approach is designed for inference about a binomial proportion and avoids relying on the usual large-sample normal approximation for the endpoint interval. The specific interval bounds are not reported in the registry record.

What does the response definition contribute?

A prespecified response definition makes the endpoint operational: it specifies which changes in lesions count as CR or PR, the requirement concerning new lesions and non-target lesions, and the imaging criteria for lymph nodes. The use of an independent central radiology review describes who evaluated response. It does not, by itself, show that assessments were complete or that there was no missing response information. Those details are not reported in the registry record.

The assessment window is stated as up to 267 days. This identifies the timeframe associated with the primary outcome, but does not give the timing or frequency of individual assessments. Those assessment details are not reported in the registry record. The endpoint is a percentage, rather than a time-to-event measure; it does not directly describe how long a response lasted. Duration of response is separately listed as a secondary outcome in Cohort A.

How should the design inform statistical interpretation?

The nonrandomized, single-arm design yields no concurrent control estimate. General statistical explanation: random allocation can help balance measured and unmeasured prognostic factors across comparison groups, while a single-arm study has no such randomized contrast. A response percentage in one cohort is therefore a description of observed outcomes in that study population, not a direct estimate of the difference caused by treatment relative to a control. The two histology cohorts do not create a valid control comparison because their disease classifications differ.

Open-label status means the study was not masked according to the registry. The record does specify independent central radiology review for the primary response assessment, but further information about assessment procedures is not reported. Masking and independent review are distinct design features; one should not infer that the whole study was blinded from the independent review statement.

What do the planning illustrations mean?

The registry's sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations use total event counts under the Schoenfeld approach; for other outcomes, they refer to participants per arm. These assumptions describe hypothetical planning calculations, not the design of this single-arm study. They are not observed power, and they do not establish the study's original sample-size justification. The original protocol rationale and its sample-size justification are not reported in the registry record. Numerical illustration results are not reported in the registry record.

General statistical explanation: over-dispersion refers to variability greater than a model assumes. It can make standard errors and confidence intervals too small if ignored. The registry endpoint is a binomial proportion and specifies an exact binomial confidence interval; no over-dispersion adjustment is reported. The record does not describe interim analyses, a detailed statistical analysis plan, or additional modeling methods. Those details are 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("Cohort A: Squamous NSCLC")
n      <- c(3)
events <- c(1)
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  Cohort A: Squamous NSCLC  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes: ORR in Cohort B; progression-free survival, duration of response, and overall survival in Cohort A; and counts of participants with treatment-emergent adverse events and treatment-related treatment-emergent adverse events according to NCI CTCAE v5.0. Listing multiple outcomes raises the general statistical issue of multiplicity: when many hypotheses are tested, the chance of at least one apparently notable result can increase. That is general context, not a claim that multiple statistical tests were performed in this study.

A multiplicity strategy, including any hierarchy, adjustment, or designation of outcomes as descriptive, is not reported in the registry record. The registry records no analyses, and it does not give p-values or hypothesis-testing results for the listed endpoints. No correction method or inferential testing plan should be inferred from the outcome list alone.

The primary endpoint population is defined as all enrolled participants who received at least 1 dose of pemigatinib. The number of participants in that population and the handling of participants without an evaluable response are not reported in the registry record. The record does not explain how missing response assessments, withdrawals, or other missing endpoint data were handled. These omissions matter because a percentage can depend on who is included in its denominator and how unevaluable outcomes are treated.

The registry's confidence interval is described as exact for a binomial distribution, but that method statement does not answer how missing outcomes were handled or whether other populations were used for sensitivity analyses. Details of missing-data methods, analysis populations beyond the stated primary definition, interim analyses, and the statistical analysis plan are not reported in the registry record.

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: acute respiratory failure (20.0%), hypotension (20.0%), pneumonia (20.0%), pulmonary sepsis (20.0%), respiratory tract infection (20.0%).

The serious adverse event counts are reported by cohort and in total. In Cohort A, 0 of 3 participants at risk were listed as having a serious adverse event. In Cohort B, 2 of 5 were listed, and overall 2 of 8 were listed. These are participant counts and denominators, not comparative estimates against a control group. The record also lists five serious-event terms, each at 20.0%: acute respiratory failure, hypotension, pneumonia, pulmonary sepsis, and respiratory tract infection. The record does not specify in this listing the count for each term or how terms overlap across participants.

Deaths are listed for 1 of 3 participants in Cohort A, 4 of 5 in Cohort B, and 5 of 8 overall. The registry figures do not establish that pemigatinib caused any serious event or death. Cohort-specific counts should be interpreted descriptively, especially because the cohorts are small and differ by histology. They are not a randomized comparison.

The registry separately lists other adverse events for 3 of 3 participants in Cohort A, 5 of 5 in Cohort B, and 8 of 8 overall. A serious event, an event classified as treatment-emergent, and an event judged treatment-related are distinct concepts. The listed serious-event counts do not tell how many events were considered treatment-related. The record names treatment-related treatment-emergent adverse events as a secondary outcome, but its result is not reported in the registry record.

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

The record documents a completed, open-label, single-arm Phase 2 study of pemigatinib in advanced NSCLC with FGFR alterations. It identifies a primary response question in the squamous cohort, gives the response criteria and assessment timeframe, and reports participant counts for safety categories. It does not report the primary ORR value, its 95% confidence interval, or the numerical findings for the listed secondary efficacy outcomes.

Thus the posted information does not allow a reader to quantify the observed primary response rate or judge its precision. It also does not support a conclusion about how outcomes compare with another treatment, because there was no comparator arm. Even if a response proportion were available, a single-arm percentage would describe outcomes among participants in the study and would not, on its own, isolate a treatment effect from other explanations.

The safety figures describe the number of participants reported in each category, including serious adverse events and deaths. They are not evidence of causation. The adverse-event counts also do not substitute for the unreported treatment-related adverse-event outcome or a complete account of event timing, severity, duration, and attribution. Those details are not reported in the registry record.

General statistical context: estimates from small cohorts tend to have substantial uncertainty, and confidence intervals are useful for showing the precision of a proportion. In this case, although the registry says an exact binomial interval was used, its numerical result is not reported. There is therefore no basis in the record to characterize the size or precision of the response estimate. The trial status and endpoint definitions should be distinguished from outcome findings: a completed study may have measured an outcome, but the registry record must report the result for it to be interpreted.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates the difference between a clearly defined endpoint and a reported endpoint result. The record specifies ORR, the population definition, the response criteria, the assessment method, and the timeframe. Those details describe what was intended to be measured. Without the observed response count, denominator, and interval limits, however, the central estimate and its uncertainty cannot be evaluated from the registry record.

The study also illustrates the limits of a single-arm design. A within-study response proportion can describe the observed cohort, but it does not provide a randomized contrast. The two cohorts are divided by histology and therefore are not a like-for-like comparison group. This distinction matters when interpreting a reported percentage: a number can be precise as a description of the enrolled cohort while still not answering a comparative treatment question.

Enrollment of 8 highlights why denominator and interval reporting are important. General statistical context: in a small cohort, each participant represents a substantial part of the observed proportion, and uncertainty can remain large even when an estimate is easy to state. The registry names an exact binomial interval, an appropriate form of interval method for a proportion, but does not provide its numerical limits.

Finally, safety counts and efficacy outcomes address different questions. Serious-event and death counts convey observed safety information, while ORR applies a radiographic response definition. Neither can be substituted for the other, and neither alone provides a causal comparison in a single-arm study. The registry's detailed outcome definitions make the intended questions legible, while the missing numerical efficacy and secondary outcome results limit what can be concluded statistically.

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 most direct limitation of interpretation is that the registry record does not report the primary ORR estimate or its 95% confidence interval. It also does not report numerical results for the secondary efficacy outcomes. Although the study is marked completed, the available record therefore does not permit evaluation of the magnitude or precision of the primary response result.

The study enrolled 8 participants and was single-arm, nonrandomized, and open-label. There is no concurrent control group, and the cohorts differ in histology. Consequently, the design cannot support a randomized treatment comparison, and comparisons between Cohort A and Cohort B would mix cohort differences with any differences in observed outcomes. The small enrollment also limits the amount of information available for estimating proportions and safety frequencies.

The primary endpoint population is defined as participants who were enrolled and received at least 1 dose, but the number analyzed and response denominator are not reported in the registry record. Missing outcome handling, response-evaluation completeness, and any sensitivity analyses are not reported. The registry also does not report the study's original sample-size justification, detailed analysis plan, interim analyses, multiplicity approach, or dose-schedule details. Planning assumptions described in the record should not be mistaken for the trial's design rationale or observed power.

The serious adverse event and death counts are descriptive. The record does not establish causal attribution from these counts, and the detailed treatment-related adverse-event results are not reported. The listed serious-event terms are accompanied by percentages, but the associated term-specific counts and overlap are not specified in the registry record. These limitations make it important to avoid drawing conclusions beyond the recorded definitions and counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Relapsed or Refractory Advanced Non-Small Cell Lung Cancer With an FGFR Alteration — NCT05253807.
• Registry record last updated 2025-08-05; status last verified 2025-08.
• Results first posted 2024-08-06.
• 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

NCT05253807 is a completed Phase 2, open-label, nonrandomized, single-arm study of pemigatinib in advanced NSCLC with an FGFR alteration. The registry lists enrollment of 8 and separates participants into squamous Cohort A and nonsquamous Cohort B. The primary endpoint was ORR in Cohort A up to 267 days, assessed by independent central radiology review using RECIST v1.1. The registry states that an exact binomial method was used for the confidence interval.

The primary ORR estimate, its interval, and numerical secondary efficacy outcomes are not reported in the registry record. Safety listings report serious adverse events in 0 of 3 participants in Cohort A and 2 of 5 in Cohort B, with 2 of 8 overall; deaths are listed in 1 of 3, 4 of 5, and 5 of 8, respectively. The single-arm design provides no randomized control comparison, and the recorded safety counts do not establish causality.