A Study of SAR444245 Combined With Cemiplimab for the Treatment of Participants With Various Advanced Skin Cancers (Pegathor Skin 201): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of SAR444245 Combined With Cemiplimab for the Treatment of Participants With Various Advanced Skin Cancers (Pegathor Skin 201) (NCT04913220), a non-randomized phase 1, phase 2 study. The primary outcome is All Cohorts: Objective Response Rate (ORR).

2. Clinical Question

The study focused on antitumor activity in participants with advanced skin cancers. Cohort A enrolled participants with melanoma, and Cohort B enrolled participants with cutaneous squamous cell carcinoma. The record also describes dose groups within those cohorts and identifies the study as Phase 1/2, open-label, non-randomized, and multi-center.

Because treatment assignment was not randomized and no control group is described, the main question is whether responses were observed among participants treated with the combination, not whether the combination performed better than another treatment. Differences between cohorts or dose groups cannot be interpreted as causal treatment effects from this design alone. The record does not report numerical response counts or an ORR estimate, so the magnitude and precision of response cannot be assessed from the registry information available.

3. Trial Design

NCT04913220 is a Phase 1/2, open-label, non-randomized, parallel-cohort study sponsored by Sanofi. The registry lists an enrollment of 46 participants and conditions of malignant melanoma and squamous cell carcinoma of skin. The study began on 2021-07-15, had a primary completion date of 2023-08-22, and is listed as terminated. The reason for termination is not reported in the registry record.

The study evaluated SAR444245, also called THOR-707, in combination with cemiplimab. Cohort A was for melanoma; Cohort B was for cutaneous squamous cell carcinoma (CSCC). Both descriptions specify administration every 3 weeks on Day 1 of each 21-day cycle for up to 35 cycles. Safety and dose-limiting toxicities were among the secondary outcomes, alongside response measures and progression-free survival.

Open-label means treatment masking was absent, and non-randomized means participants were not assigned to groups by random allocation. The record lists dose-specific groups within each disease cohort, but those groups should not be treated as randomized comparisons. Differences may reflect participant characteristics, cohort composition, or other factors as well as dose.

The registry does not report the rationale for the enrollment target, the dose-selection procedure, or the detailed statistical analysis plan. It also does not report interim-analysis procedures. The registry lists 13 outcome measures and 0 analyses. Numerical results for the primary endpoint are not reported in the registry record, so the study's response findings cannot be assessed from the information in this 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.

Before assignment: The study was terminated based on strategic sponsor decision not driven by any safety concerns. Note: Reason for not completed = Reason for permanent full intervention discontinuation.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The efficacy population consisted of all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.

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: The exposed population consisted of all participants who had given their informed consent and received at least one dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as All Cohorts: Objective Response Rate (ORR), measured over From first dose of study treatment administration (Day 1) up to approximately 25 months (Cohorts A and B).

The primary endpoint was objective response rate (ORR), expressed as the percentage of participants whose best overall response was a confirmed complete response (CR) or partial response (PR). Tumor response was assessed using RECIST version 1.1 or modified WHO response criteria. A CR was defined as disappearance of all target lesions, with any pathological lymph nodes reducing in short axis to <10 millimeter (<1 centimeter). A PR required at least a 30% decrease in the sum of target-lesion diameters relative to the baseline sum.

ORR is used to describe the proportion of participants with a specified degree of tumor shrinkage. It does not, by itself, describe how long a response lasts, whether disease remains controlled over time, or how outcomes compare with another treatment. The registry lists duration of response, time to response, complete response rate, clinical benefit rate, and progression-free survival among secondary outcomes, but their numerical results are not reported in the registry record.

The stated timeframe for ORR was from the first dose on Day 1 up to approximately 25 months for Cohorts A and B. The efficacy population included exposed participants with at least one evaluable post-baseline tumor assessment or those who permanently discontinued study treatment. The registry does not report the number included in this population, the observed ORR, or its confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help define what an endpoint estimates, how uncertainty is represented, and what comparisons a study design can support. For NCT04913220, the registry identifies a percentage-based primary endpoint and a 90% confidence interval as its dispersion measure. However, it does not report the numerical ORR result, the interval limits, or a detailed statistical analysis plan.

What does a percentage endpoint represent?

General: A percentage endpoint describes the share of participants in a defined analysis population who meet a specified event or response definition. The numerator is the number meeting that definition, and the denominator is the number assessed in the analysis population. Interpretation depends on clear response criteria, a defined observation period, and transparent reporting of who was included. In this study, ORR was based on confirmed CR or PR under RECIST version 1.1 or modified WHO criteria. The registry defines the efficacy population but does not report its size or the response count.

How should a confidence interval be read?

General: A confidence interval expresses statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not remove possible bias from the study design, missing outcomes, measurement, or participant selection. The registry specifies a 90% confidence interval for ORR, but its endpoints are not reported in the registry record. Without the estimate and interval limits, neither the observed response proportion nor its precision can be evaluated.

What can a non-randomized design establish?

General: Random allocation helps make groups comparable, on average, with respect to measured and unmeasured baseline factors. In a non-randomized study, that protection is absent. Descriptive outcome estimates can still characterize the treated participants, but differences between groups may reflect differences in who entered each group as well as differences in treatment. Here, cohort membership was based on disease categories and the registry identifies dose-specific groups. The record explicitly cautions that arms are not like-for-like control comparisons. Therefore, between-group contrasts should not be treated as randomized estimates of treatment effect.

Open-label status means participants and study personnel were not masked to treatment assignment. General: Lack of masking can influence reporting, clinical management, or assessment, depending on the endpoint and procedures. Tumor response criteria provide defined rules for classifying response, but the registry record does not report details of independent review, assessment scheduling beyond the stated timeframe, or other safeguards that may affect assessment.

What does the planning illustration mean?

General: Sample-size planning describes the number of participants that might be needed under chosen assumptions to detect a specified effect with a chosen level of statistical error and power. The registry record does not report the trial's own sample-size justification. The planning assumptions associated with the posted calculations describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those are planning assumptions, not evidence that the trial used that design or analysis. Any sample sizes from such calculations are planning illustrations, not observed power, and do not establish what the trial was capable of detecting under its actual conduct.

General: Over-dispersion occurs when outcome variability is greater than expected under a model's assumptions. If ignored, standard errors may be understated and uncertainty may appear too small. The record does not report a model for over-dispersion or a statistical approach to account for it. For a percentage endpoint, the relevant model and uncertainty method should be stated if modeled estimates are used; the registry's endpoint description alone does not establish those details.

Why does the analysis population matter?

The efficacy population was defined as exposed participants with at least one evaluable post-baseline tumor assessment or participants who permanently discontinued study treatment. This definition identifies who could contribute to efficacy analyses, but the record does not state how particular cases were handled when a post-baseline assessment was absent, incomplete, or unevaluable. General: Different missing-data approaches can yield different estimates, especially if missingness is related to health status or treatment discontinuation. Clear reporting of participant flow, missingness, and sensitivity analyses is therefore important. Those details are not reported in the registry record.

The registry lists 13 outcome measures and 0 analyses. It identifies ORR as primary and lists several secondary response, safety, and time-to-event outcomes, but does not describe multiplicity adjustment or the statistical hierarchy among outcomes. General: Testing multiple outcomes can increase the chance of a statistically significant finding occurring by chance if results are interpreted without accounting for the number and relationship of tests. The record does not allow assessment of whether any such adjustment was planned or applied.

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:1L Melanoma ICI-naïve: Pegenzileukin 16 m", "Cohort A:1L Melanoma ICI-naïve: Pegenzileukin 24 m", "Cohort B: 1-3L CSCC ICI-naïve: Pegenzileukin 16 mc", "Cohort B: 1-3L CSCC ICI-naïve: Pegenzileukin 24 mc")
n      <- c(20, 7, 16, 3)
events <- c(8, 4, 9, 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 A:1L Melanoma ICI-naïve: Pegenzileukin 16 m  20  8  40.0  19.1  63.9  21.9  61.3  21.8  61.6
ARM  Cohort A:1L Melanoma ICI-naïve: Pegenzileukin 24 m  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3
ARM  Cohort B: 1-3L CSCC ICI-naïve: Pegenzileukin 16 mc  16  9  56.2  29.9  80.2  33.2  76.9  32.9  77.0
ARM  Cohort B: 1-3L CSCC ICI-naïve: Pegenzileukin 24 mc  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists ORR as the primary outcome and includes secondary measures of adverse events, dose-limiting toxicities, complete response, time to complete response, time to response, duration of response, clinical benefit rate, and progression-free survival. It lists 13 outcome measures and 0 analyses. The statistical hierarchy among outcomes, planned hypothesis tests, and any adjustment for multiple comparisons are not reported in the registry record.

General: When a study evaluates multiple outcomes or makes multiple comparisons, the chance of at least one apparently unusual result can increase if every result is interpreted as an independent confirmatory test. Prespecified primary and secondary outcomes, together with a stated multiplicity strategy, help distinguish confirmatory inference from exploratory description. The available record does not describe such a strategy, so the intended inferential status of secondary findings cannot be determined.

The defined efficacy population included exposed participants with at least one evaluable post-baseline tumor assessment or those who permanently discontinued study treatment. The record does not report its size, participant flow into that population, missing-assessment counts, or the method used to handle missing response data. It also does not report sensitivity analyses addressing missing outcomes. General: Missing-data assumptions matter because the response estimate can depend on which participants have assessable outcomes and how absent outcomes are treated.

The registry does not report a full statistical analysis plan, interim-analysis procedures, or the trial's sample-size justification. The reason for termination is also not reported in the registry record. These omissions limit assessment of prespecification and of how the recorded outcomes relate to the study's planned analyses.

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: cytokine release syndrome (42.9%), infusion related reaction (33.3%), immune-mediated myocarditis (15.0%), immune-mediated enterocolitis (14.3%), pyrexia (14.3%).

The safety record presents groups by disease cohort and dose, with counts at risk and counts affected for serious adverse events, other adverse events, and deaths. For Cohort A, 1L melanoma ICI-naïve, the Pegenzileukin 16 mcg/kg plus Cemiplimab group lists 20 at risk for serious events and 11 affected, 20 at risk for other events and 19 affected, and 5 deaths. The Pegenzileukin 24 mcg/kg plus Cemiplimab group lists 7 at risk and 4 affected for serious events, 7 at risk and 7 affected for other events, and 2 deaths.

For Cohort B, 1-3L CSCC ICI-naïve, the Pegenzileukin 16 mcg/kg plus Cemiplimab group lists 16 at risk and 8 affected for serious events, 16 at risk and 16 affected for other events, and 2 deaths. The Pegenzileukin 24 mcg/kg plus Cemiplimab group lists 3 at risk and 1 affected for serious events, 3 at risk and 3 affected for other events, and 0 deaths.

The registry also lists selected serious-event terms with percentages: Cytokine Release Syndrome, 42.9%; Infusion Related Reaction, 33.3%; Immune-Mediated Myocarditis, 15.0%; Immune-Mediated Enterocolitis, 14.3%; Pyrexia, 14.3%; and Lymphocyte Count Decreased, 14.3%. The denominator and event-specific counting method for these percentages are not reported in the registry record. The groups differ in size and are non-randomized; these figures should not be interpreted as comparative treatment effects or pooled risks.

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

The registry record establishes that a Phase 1/2, open-label, non-randomized study evaluated SAR444245 with cemiplimab in melanoma and CSCC cohorts. It defines ORR as the primary endpoint and specifies tumor-response criteria and an observation timeframe. It also reports selected safety counts by dose and cohort. These details describe what the study set out to assess and some of the recorded safety information.

The record does not report the numerical ORR, response counts, or the stated 90% confidence interval. Therefore, it does not allow readers to judge the observed response frequency or how precise that estimate was. This lack of a numerical result is not evidence that the response rate was zero or that no responses occurred. It is a limit on what can be concluded from the registry record.

The non-randomized design does not provide a randomized control comparison. Even if cohort results were available, differences between them would not alone show that a dose or treatment caused better or worse outcomes. Disease cohort and dose-group membership, participant mix, and other factors may differ. Open-label conduct is another design feature to consider when interpreting outcomes, although the record does not specify how assessments were independently reviewed.

The safety counts describe events in the listed groups; they do not establish that treatment caused an event, nor do they support direct comparisons between groups with different sizes and disease cohorts. The registry lists the study status as terminated, but does not report the reason. No inference about the termination rationale is warranted from status alone.

In short, the registry supports a description of the study design, endpoint definitions, and selected safety entries. It does not support a conclusion about the magnitude or certainty of the primary efficacy result, comparative benefit, or the reason the study ended. Those questions require information not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it brings together two disease cohorts and dose groups within a non-randomized, open-label design. Such studies can describe outcomes in treated participants and can contribute information about response definitions, safety reporting, and feasibility. They do not provide the same basis for causal comparisons as a randomized trial with a control group. That distinction is central when interpreting results across cohorts or dose groups.

The primary endpoint is a percentage based on confirmed complete or partial response, with explicit criteria and a stated timeframe. Those definitions make clear what counts as response, but they do not substitute for numerical results. The registry record identifies the endpoint and a confidence-interval measure while leaving the estimate and its interval unreported. As a result, an important statistical distinction remains unavailable: not only what response level was observed, but also how uncertain that estimate was.

The record also illustrates why analysis populations and missing-data handling matter. It defines the efficacy population, but does not report its size, participant flow, missing assessments, or the approach to missing outcomes. These details affect how readers understand the denominator and possible selection into the response analysis.

Finally, safety counts are separated by cohort and dose, while the groups are not randomized and vary in size. Keeping those descriptions separate avoids suggesting a controlled comparison that the design does not support. The registry status is terminated, but its reason is not stated. Together, these features underscore the importance of transparent reporting of endpoint estimates, uncertainty, analysis methods, and trial status context.

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.

A central limitation is that the registry record does not report the primary ORR estimate, response counts, or confidence-interval limits. It therefore does not support an assessment of observed efficacy or its statistical precision. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study was non-randomized and open-label, with disease-specific cohorts and dose groups rather than a randomized control comparison. Any apparent differences among groups would be vulnerable to differences in participant composition and other factors. The record does not describe adjustment methods that could address such differences, and does not report the detailed analysis plan.

The registry defines an efficacy population but does not report its size, participant flow, or the handling of missing or unevaluable tumor assessments. It does not report whether response was assessed by independent review. These omissions limit interpretation of the endpoint denominator and assessment procedures.

The record lists selected safety counts and serious-event percentages, but the denominator and counting method for the displayed serious-event percentages are not reported in the registry record. Safety figures are divided across groups of varying sizes, and should not be read as randomized comparisons. The serious-event group labels use Pegenzileukin, while the study intervention descriptions identify SAR444245 and THOR-707; the relationship between this naming in the safety entries and intervention descriptions is not explained in the registry record.

The trial is listed as terminated, but the reason is not reported. The registry also does not report the sample-size justification, interim-analysis procedures, multiplicity strategy, or a full statistical analysis plan. These gaps prevent fuller evaluation of the study's planned inference and the context for its recorded status.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of SAR444245 Combined With Cemiplimab for the Treatment of Participants With Various Advanced Skin Cancers (Pegathor Skin 201) — NCT04913220.
• Registry record last updated 2026-02-04; status last verified 2025-12.
• Results first posted 2026-02-04.
• 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

NCT04913220 evaluated SAR444245, also called THOR-707, combined with cemiplimab in advanced skin cancers. The study was Phase 1/2, open-label, non-randomized, and multi-center, with melanoma and CSCC cohorts. Enrollment was 46. Treatment was described every 3 weeks on Day 1 of each 21-day cycle for up to 35 cycles. The study began on 2021-07-15, had a primary completion date of 2023-08-22, and is listed as terminated.

The primary endpoint was ORR, defined by confirmed CR or PR under RECIST version 1.1 or modified WHO criteria, with a 90% confidence interval specified. The numerical ORR result and interval are not reported in the registry record. Selected safety counts are reported by cohort and dose, but they do not constitute randomized comparisons. The reason for termination, sample-size justification, missing-data procedures, multiplicity approach, and full statistical analysis plan are not reported in the registry record.