Cemiplimab in AlloSCT/SOT Recipients With CSCC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cemiplimab in AlloSCT/SOT Recipients With CSCC (NCT04339062), a non-randomized phase 1, phase 2 study. The primary outcome is Rate of Renal Transplant Rejection (Cohort 2) or GVHD (Cohort 1)..

2. Clinical Question

3. Trial Design

This completed phase 1 and phase 2 study evaluated cemiplimab in selected organ transplant recipients with advanced cutaneous squamous cell carcinoma. The registry lists an enrollment of 12 and a non-randomized, unmasked, parallel design. Enrollment began on 2020-11-03, and primary completion was 2023-06-12. The study status is completed.

The trial separated participants according to transplant history. Cohort 1 comprised people who had received an allogeneic hematopoietic stem cell transplant and was assigned cemiplimab. Cohort 2 comprised kidney transplant recipients and received cemiplimab with everolimus or sirolimus and prednisone. Cemiplimab was administered intravenously at a predetermined flat dosage every 21 days. The registry says everolimus or sirolimus began before the first cemiplimab dose and continued daily while cemiplimab was received. The complete prednisone schedule is not reported in the registry record.

This is not a randomized comparison of treatment strategies. Transplant history determines cohort membership, and the kidney cohort has additional medicines in its listed regimen. The groups therefore differ in clinically relevant ways as well as in their treatment descriptions. An observed difference between them could not be attributed to a specific drug or regimen using this design alone.

The registry lists five outcome measures, including progression-free survival, overall survival, overall response rate, and duration of response among the secondary outcomes. The primary outcome is graft-versus-host disease in Cohort 1 or renal transplant rejection in Cohort 2, measured as a percentage of participants during the stated follow-up window. No patients enrolled into Cohort 1, and a primary endpoint result is not reported in the registry record. Details of a statistical analysis plan, sample-size justification, or interim analyses 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: No patients enrolled into Cohort 1

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: No patients were enrolled into Cohort 1.

6. Primary Endpoint

The registry lists the primary outcome as Rate of Renal Transplant Rejection (Cohort 2) or GVHD (Cohort 1)., measured over First dose of study treatment up to 100 days.

The primary endpoint measures the percentage of participants who experience graft-versus-host disease in Cohort 1 or renal transplant rejection in Cohort 2. It covers the period from the first dose of study treatment through 100 days. These are different events tied to the participants’ transplant types, rather than a single identical event assessed in both cohorts.

A percentage expresses how often an event occurred among the participants evaluated for that endpoint. A confidence interval describes uncertainty around an estimated percentage: a narrower interval indicates greater precision, while a wider interval indicates less precision. The registry identifies a 90% confidence interval as the endpoint’s dispersion measure, but the endpoint estimate and its interval are not reported in the registry record.

This endpoint is used to describe an important safety concern in transplant recipients receiving the study regimen. It is not, by itself, a comparison against an untreated group or another randomized regimen. The absence of enrolled participants in Cohort 1 means no Cohort 1 event proportion can be estimated from enrolled participants. For Cohort 2, the registry record does not report a primary endpoint estimate, so the posted record cannot establish the observed rejection rate or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage measure?

The primary endpoint is expressed as a percentage of participants. In general, a percentage describes the share of an evaluated group that experienced a specified event. Its meaning depends on the event definition, the population included, and the observation period. For this study, the defined events differ by cohort: graft-versus-host disease for the allogeneic stem cell transplant cohort and renal transplant rejection for the kidney transplant cohort. The endpoint window begins at the first dose and extends through 100 days.

A percentage is descriptive unless the design and analysis support a comparison. It does not on its own show whether an intervention caused an event, how the event rate compares with an alternative, or whether an observed value is compatible with chance variation. Here, there is no randomized control group, and the primary endpoint result is not reported in the registry record. The endpoint definition can therefore be described, but its observed frequency and precision cannot.

What does a confidence interval add?

In general, a confidence interval presents a range of values that are compatible with the data under the statistical method used. It communicates uncertainty in an estimate, rather than converting the estimate into a guarantee about the true value. A wide interval indicates relatively low precision; a narrow interval indicates greater precision, given the method and data. The registry specifies a 90% confidence interval for the primary endpoint, but does not report the endpoint estimate or interval. It is therefore not possible to assess the precision of the endpoint from the registry record.

Confidence intervals are also affected by how many participants contribute information and how many events occur. A small amount of information will generally permit less precise estimates than a larger amount, although the exact precision depends on the data and method. Cohort 1 had no enrolled participants, so there is no cohort estimate to which an interval could be attached. The kidney cohort’s primary endpoint result is not reported, so no interval can be interpreted for that outcome either.

How should the non-randomized design be understood?

Random allocation is one way to make comparison groups more similar, on average, with respect to factors that may influence outcomes. This study was non-randomized. Cohort membership followed transplant history, and the kidney cohort had a regimen including everolimus or sirolimus and prednisone alongside cemiplimab. Those design features mean that the cohorts are not interchangeable control groups. Even if outcomes were reported for each cohort, a contrast between them would combine differences in transplant history and regimen rather than isolate a cemiplimab effect.

The study was also unmasked. Masking can limit the influence of knowledge about treatment assignment on some assessments or decisions. The registry does not report further information about how outcomes were assessed or whether any assessment procedures addressed this concern. A reader should not assume safeguards or analytic adjustments that are not reported in the registry record.

What do the planning assumptions mean?

General sample-size calculations ask how much information a planned study might need to detect a specified effect under stated assumptions. The registry’s planning description uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a description of the actual allocation in this non-randomized study.

The planning description also distinguishes event totals for time-to-event calculations, using the Schoenfeld method, from participants per arm for other calculations. Such illustrations are conditional on their assumptions and are not evidence that a study had a particular probability of detecting an effect after it was conducted. They are never observed power. The registry record does not report the trial’s own sample-size justification or statistical plan. No numerical planning result should be treated as a trial result.

Why do analysis populations matter?

An analysis population is the set of participants included in a particular outcome calculation. Its definition can affect the estimate, especially when participants have incomplete follow-up, do not receive planned treatment, or are excluded for other reasons. For an event percentage, the denominator needs to correspond to the defined population and follow-up rules. The registry record describes the endpoint population as participants evaluated from their first treatment, but does not report a full analysis-population definition or endpoint denominator. It also does not report missing-data methods.

The safety summaries list 12 participants at risk in Cohort 2 for serious adverse events and 12 at risk for other adverse events. Those stated groups are the basis for reading the corresponding summaries; they should not be assumed to be the analysis populations for every efficacy or primary endpoint measure. The record does not provide outcome-specific participant flow or missingness information.

What can be inferred from the posted analyses?

The registry lists zero analyses. This means the record does not provide inferential estimates, p-values, or confidence intervals for the listed efficacy outcomes. A registered outcome name is not itself evidence of a result. Similarly, adverse-event counts and term percentages are descriptive summaries, not tests of a treatment contrast. Without a reported analysis and its methods, readers cannot determine whether an outcome comparison was adjusted, how missing observations were handled, or how uncertainty was quantified.

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 2 Cemiplimab + Everolimus/Sirolimus + Predn")
n      <- c(12)
events <- c(0)
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 2 Cemiplimab + Everolimus/Sirolimus + Predn  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including a primary safety endpoint and secondary outcomes of progression-free survival, overall survival, overall response rate, and duration of response. When multiple outcomes are examined, the chance of observing at least one apparently notable result can increase if each is assessed independently. General statistical approaches can address this multiplicity, for example by adjusting inference or identifying a primary outcome in advance. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or a statistical analysis plan. It also lists zero analyses, so no inferential results are available to assess.

Missing data can affect both the estimated event frequency and its uncertainty. For example, incomplete follow-up may make it unclear whether an event occurred during the defined observation window. In general, analysis choices about missingness depend on why information is missing and on the outcome. The registry record does not report missing-data methods, outcome-specific completeness, or a detailed flow of participants through the analyses. The primary endpoint description says participants are evaluable from their first treatment, but does not provide enough detail to reconstruct an analysis population.

There were no patients enrolled into Cohort 1. That is not ordinary missing outcome information among enrolled participants; it means there are no enrolled Cohort 1 observations from which to estimate the cohort’s endpoint frequency. The primary endpoint result is not reported for Cohort 2 either. These limitations prevent assessment of the primary endpoint’s estimated value, uncertainty, and any multiplicity-adjusted inference.

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: upper respiratory infection (33.3%), lung infection (16.7%), thromboembolic event (16.7%), anemia (8.3%), atrial fibrillation (8.3%).

The registry reports serious adverse events for Cohort 2, with 12 participants at risk and 9 affected. For other adverse events, it reports 12 at risk and 12 affected. It also reports 5 deaths. These figures are descriptive summaries. They should be read as counts in the posted safety record, not as estimates of the risk attributable to a particular drug or as comparisons with another treatment group.

The listed serious-event terms and percentages are upper respiratory infection at 33.3%, lung infection at 16.7%, thromboembolic event at 16.7%, anemia at 8.3%, atrial fibrillation at 8.3%, and cardiac stent placement at 8.3%. The registry record does not report event definitions, individual event timing, or causal judgments for these terms. A term-level percentage also does not establish that the event was caused by treatment.

No safety participants are reported for Cohort 1, consistent with no patients enrolled in that cohort. The primary endpoint is specifically transplant rejection or graft-versus-host disease during the stated window, and its result is not reported in the registry record. The general adverse-event counts should not be substituted for that endpoint.

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

The record establishes that this completed study evaluated cemiplimab in selected organ transplant recipients with advanced cutaneous squamous cell carcinoma, using separate transplant-specific cohorts. It documents the intended treatment regimens and gives descriptive safety summaries for the kidney transplant cohort. Those summaries include serious adverse events, other adverse events, deaths, and selected serious-event terms with percentages.

It does not establish a causal effect of cemiplimab or the accompanying medicines. The trial was non-randomized and unmasked, with no like-for-like control comparison. Cohort 1 and Cohort 2 differ by transplant history and treatment regimen, and no patients enrolled into Cohort 1. The posted safety figures therefore cannot be interpreted as a randomized comparison between regimens or as a direct estimate of what would have happened under an alternative treatment.

The primary outcome is defined, but an observed result and its 90% confidence interval are not reported in the registry record. The record consequently does not give a numerical estimate of renal transplant rejection in Cohort 2 or graft-versus-host disease in Cohort 1 during the stated period. The absence of Cohort 1 participants also prevents an estimate for that cohort from enrolled participants.

Although the registry identifies progression-free survival, overall survival, overall response rate, and duration of response as secondary outcomes, their numerical results are not reported in the registry record. The record lists zero analyses. It therefore does not support conclusions about efficacy, comparative benefit, or the statistical significance of those outcomes. The completed status does not fill these reporting gaps.

The appropriate reading is descriptive and limited to the information recorded. The adverse-event summaries identify events reported in the kidney cohort, but do not establish cause, comparative risk, or a treatment effect. Planning calculations based on an observed effect, if considered, are design illustrations rather than evidence of observed power or clinical effectiveness.

14. Why This Trial Matters Statistically

This study raises a statistical challenge that is important in transplant research: the safety question depends on transplant type, while the cohorts do not form a randomized comparison. The endpoint combines transplant-specific events, graft-versus-host disease for the allogeneic hematopoietic stem cell transplant cohort and rejection for the kidney transplant cohort. Those events are relevant to different populations, so their rates cannot be treated as directly interchangeable measures.

The enrollment pattern matters. No patients enrolled into Cohort 1, leaving the study without observed cohort data for the graft-versus-host disease component of its primary endpoint. The posted safety summaries describe Cohort 2, but the primary endpoint result is not reported in the registry record. This illustrates why a registered endpoint and a completed study do not necessarily provide an interpretable estimate of the endpoint.

The study also illustrates the distinction between descriptive safety reporting and causal inference. Counts and event percentages can show what was recorded among participants in a cohort. Without randomization or a suitable comparator, they cannot isolate the contribution of a particular drug or regimen. Different transplant histories and treatment components further complicate direct comparisons between the cohorts.

Finally, the record underscores the role of transparent analysis reporting. Details about the analysis plan, missing data, analysis populations, and multiplicity are not reported in the registry record, and the record lists zero analyses. Without endpoint estimates and uncertainty measures, readers cannot judge precision or assess inferential claims. Reporting participant flow, outcome-specific denominators, and prespecified analytic methods would be essential for interpreting the outcomes, but those details are not reported in the registry record.

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 strongest trial-specific limitation is that no patients enrolled into Cohort 1. The study therefore has no enrolled participant data for estimating the graft-versus-host disease component of the primary endpoint. The registry does not report the primary endpoint estimate for Cohort 2, either, so the primary safety question lacks a posted estimate and confidence interval.

The enrollment was 12, and the posted safety group for Cohort 2 lists 12 participants at risk. This limited enrollment constrains the amount of information available for describing uncommon events and estimating precise event frequencies. The record does not provide the endpoint-specific denominator or an interval for the safety estimates, so their precision cannot be evaluated from the registry record.

The non-randomized design and lack of masking limit causal interpretation. Cohort membership follows transplant history, and the listed regimen for kidney transplant recipients includes everolimus or sirolimus and prednisone in addition to cemiplimab. Cohort differences cannot be attributed to a single treatment component. The cohorts are not a like-for-like control comparison.

The registry record does not report a statistical analysis plan, sample-size justification, missing-data approach, multiplicity strategy, or detailed analysis populations. It lists zero analyses, and numerical results for the secondary outcomes are not reported in the registry record. The prednisone schedule is also incomplete in the registry description. These reporting gaps limit assessment of endpoint definitions in practice, analytic decisions, uncertainty, and the interpretation of the posted safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cemiplimab in AlloSCT/SOT Recipients With CSCC — NCT04339062.
• Registry record last updated 2025-04-23; status last verified 2025-04.
• Results first posted 2024-06-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed phase 1 and phase 2, non-randomized, unmasked, parallel study of cemiplimab in selected organ transplant recipients with advanced cutaneous squamous cell carcinoma. Enrollment was 12. Cohort 1 involved people with an allogeneic hematopoietic stem cell transplant; Cohort 2 involved kidney transplant recipients and included cemiplimab with everolimus or sirolimus and prednisone. No patients enrolled into Cohort 1.

The primary endpoint was the percentage of participants with graft-versus-host disease in Cohort 1 or renal transplant rejection in Cohort 2, from the first dose through 100 days, with a 90% confidence interval specified. Its result is not reported in the registry record. Cohort 2 safety summaries report 9 participants affected by serious adverse events, 12 affected by other adverse events, and 5 deaths. The record lists five outcome measures and zero analyses. Numerical results for the secondary outcomes are not reported in the registry record.