A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202) (NCT04914897), a non-randomized phase 2 study. The primary outcome is Cohorts A1 and A2: Objective Response Rate (ORR).

2. Clinical Question

3. Trial Design

This was a phase 2, non-randomized, open-label, parallel, multi-cohort, multi-center study of SAR444245 combined with other anticancer therapies. The registry lists 106 participants enrolled and describes four cohorts: A1, A2, B1, and C1. The study status is terminated. The recorded start date is 2021-09-23, and the primary completion date is 2023-07-18.

Cohorts A1 and A2 covered previously untreated Stage IV NSCLC. A1 required PD-L1 TPS of at least 50%, while A2 covered PD-L1 TPS of 1%-49%; both were described as first-line pegenzileukin plus pembrolizumab treatment. Cohort B1 covered NSCLC in situations where standard of care was not in the participant’s best interest or no standard of care was established, with the treatment described as second- or third-line. Cohort C1 covered mesothelioma with no established standard of care and progression during or after at least one but no more than 2 prior regimens, also described as second- or third-line.

Because treatment assignment was not randomized and masking was absent, the study was not designed as a blinded comparison against a concurrent randomized control. Cohort membership reflected disease and treatment-history criteria. Consequently, comparisons across cohorts could reflect differences in those characteristics as well as any differences in outcomes. The registry record does not report a control group, a randomization procedure, or a formal comparative estimand.

The primary endpoint was specified for cohorts A1 and A2 only. Secondary outcomes listed for all cohorts included adverse events, dose-limiting toxicities, response timing and duration, clinical benefit rate, progression-free survival, and pegenzileukin plasma concentrations. The registry record does not report a statistical analysis plan, the rationale for the enrollment target, or further details about the study’s conduct beyond the listed design and dates.

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. The Cohorts B2 and A3 were not initiated and no participants were enrolled. 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 (pegenzileukin or other anticancer therapies).

6. Primary Endpoint

The registry lists the primary outcome as Cohorts A1 and A2: Objective Response Rate (ORR), measured over From first dose of study treatment administration (Day 1) up to approximately 21 months.

Objective response rate is the percentage of participants who have a confirmed complete response or partial response. In this study, response was defined using RECIST version 1.1. A complete response required disappearance of all target lesions and reduction of pathological lymph nodes, whether target or non-target, to less than 10 mm in short axis. A partial response required at least a 30% decrease in the sum of target-lesion diameters from baseline.

ORR is used as a measure of tumor shrinkage meeting prespecified response criteria. It summarizes whether participants experienced a confirmed response during the assessment period; it does not, by itself, describe how long a response lasted or how long participants lived without progression. Those are distinct outcomes, and the registry lists duration of response and progression-free survival separately as secondary outcomes.

The specified timeframe ran from the first dose of study treatment on Day 1 up to approximately 21 months. The efficacy population included exposed participants with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment. The registry record does not report the number of participants in that efficacy population, the number with confirmed responses, the ORR estimate, or its 90% confidence interval. Therefore, the endpoint definition is available, but its observed result cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on distinguishing the study question from the evidence actually recorded. The study’s stated primary objective concerned antitumor activity, and the primary endpoint for cohorts A1 and A2 was ORR. The record defines how response would be classified, but does not include an observed ORR estimate, response count, or confidence interval. Without those results, there is no numerical efficacy estimate to interpret. The count of 0 analyses recorded reinforces that the registry record does not report a primary endpoint analysis.

What does a confidence interval convey?

In general, a confidence interval describes statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The registry specifies a 90% confidence interval for the primary endpoint, but no interval limits are reported. The method used to calculate that interval is also not reported in the registry record, so it is not possible to assess its assumptions or reproduce the reported analysis from this record.

For a percentage such as ORR, the estimate depends on the response count and the analysis population denominator. The registry defines the efficacy population as exposed participants with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment. It does not report the size of this population or how many participants met response criteria. Counts reported for adverse events should not be substituted as the ORR denominator: the safety counts are presented by cohort and serve a different purpose.

Why does the design matter?

In general, random assignment helps balance measured and unmeasured participant characteristics between treatment groups, supporting a causal comparison. This study was non-randomized and open-label, and the registry describes distinct cohorts rather than a randomized control comparison. The cohorts differed in disease type, PD-L1 status, treatment line, or eligibility context. Therefore, a direct comparison across those cohorts would be vulnerable to confounding by those differences. The record does not report a comparative estimate or a statistical adjustment strategy.

Open-label describes a study in which masking is absent. In general, knowledge of treatment can influence some aspects of care, assessment, or reporting. The registry identifies RECIST version 1.1 response criteria, but does not report whether response assessments were centrally reviewed or blinded. Such assessment details are not reported in the registry record.

How should the adverse-event counts be read?

The adverse-event figures are descriptive counts among participants at risk in each cohort. In general, a count should be interpreted with its corresponding denominator and event definition. The listed serious adverse event counts are 6 of 17 in A1, 11 of 20 in A2, 21 of 40 in B1, and 13 of 29 in C1. The listed counts for other adverse events are 16 of 17, 18 of 20, 38 of 40, and 27 of 29, respectively. These counts do not establish that one cohort had a higher treatment-related risk than another: participants were not randomized to the cohorts, and cohort composition differed. The registry record does not provide adjusted comparisons or uncertainty intervals for these counts.

Over-dispersion is a general statistical issue that arises when observed variability is greater than a model assumes. If a model assumes outcomes vary less than they actually do, standard errors and confidence intervals can be too optimistic. The record does not report a model for the primary endpoint or any assessment of over-dispersion, so this issue cannot be evaluated as part of the study’s reported analysis.

What can planning calculations establish?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. It is not an observed treatment effect and is not a substitute for an outcome analysis. The assumptions described for the planning illustration specify a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. The illustration is not the trial’s own design justification; the registry record does not report the study’s sample-size justification. Planning calculations should not be described as observed power.

The registry does not report the statistical method for the primary endpoint, hypothesis-testing details, model covariates, sensitivity analyses, interim analyses, or a prespecified analysis plan. Those items are not reported in the registry record. The absence of those details limits independent assessment of how the endpoint was analyzed, but it does not authorize assuming a particular method.

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 A1:NSCLC, PD-L1 TPS >=50%:Pegenzileukin 24 ", "Cohort A2:NSCLC, PD-L1 TPS 1%-49%:Pegenzileukin 24")
n      <- c(17, 20)
events <- c(7, 3)
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 A1:NSCLC, PD-L1 TPS >=50%:Pegenzileukin 24   17  7  41.2  18.4  67.1  21.6  64.0  21.5  64.3
ARM  Cohort A2:NSCLC, PD-L1 TPS 1%-49%:Pegenzileukin 24  20  3  15.0  3.2  37.9  5.2  36.0  5.4  36.3

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study makes several statistical comparisons or tests several outcomes: the chance of at least one false-positive finding can increase unless the testing strategy accounts for this. This trial listed multiple secondary outcomes, including safety, dose-limiting toxicities, response measures, progression-free survival, and pharmacokinetic outcomes. However, the registry record does not report a multiplicity strategy, a hierarchy among outcomes, or whether any findings were intended to be confirmatory. The record also does not report a statistical analysis plan. No adjustment or testing sequence should be inferred.

The primary endpoint applies to cohorts A1 and A2. The record does not explain how missing or unevaluable tumor assessments were handled, beyond defining the efficacy population as exposed participants with at least one evaluable post-baseline tumor assessment or those who permanently discontinued study treatment. It does not state how participants without an evaluable assessment were counted, how incomplete assessments were addressed, or whether any sensitivity analyses were performed. Those details are not reported in the registry record.

The analysis population definition matters because the response percentage depends on who is included in its denominator. Since the record does not give the efficacy-population size or the response count, the endpoint estimate cannot be reconstructed. The registry lists 106 enrolled participants overall, but that total is not the reported denominator for the primary efficacy analysis. No assumption should be made that all enrolled participants were included in that analysis.

Reasons for termination, data cut-off details, and any consequences of termination for missing outcome data are also not reported in the registry record. The record does not describe interim analyses or stopping rules. These omissions prevent assessment of whether outcome availability or the timing of analyses could have influenced the reported results.

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 (17.5%), infusion related reaction (11.8%), pleural effusion (10.3%), ischaemic stroke (6.9%), malignant ascites (6.9%).

The safety figures are presented by cohort as counts of participants with serious adverse events and with other adverse events. The serious adverse event counts are 6 of 17 in A1, 11 of 20 in A2, 21 of 40 in B1, and 13 of 29 in C1. The counts for other adverse events are 16 of 17, 18 of 20, 38 of 40, and 27 of 29, respectively. These denominators are cohort-specific and should be kept alongside the counts when interpreting them.

The registry also lists deaths by cohort: 3 in A1, 13 in A2, 26 in B1, and 18 in C1. The record does not specify in this summary whether these deaths were considered treatment-related, nor does it provide causes or timing. They should not be interpreted as deaths caused by the study treatment.

Listed serious adverse event terms and percentages include Cytokine Release Syndrome at 17.5%, Infusion Related Reaction at 11.8%, Pleural Effusion at 10.3%, Ischaemic Stroke at 6.9%, Malignant Ascites at 6.9%, and Infection at 5.9%. These are descriptive figures in the registry record. They do not establish comparative safety against another treatment, and the non-randomized cohorts are not suitable like-for-like controls. The record does not report adjusted risk comparisons or confidence intervals for these safety summaries.

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

The registry record describes a phase 2 study that evaluated SAR444245 combined with other anticancer therapies in several lung cancer and mesothelioma cohorts. Its primary efficacy endpoint was ORR for cohorts A1 and A2, defined by confirmed complete or partial response under RECIST version 1.1. The endpoint definition explains what the study intended to measure; it does not show what the study found.

No primary ORR estimate, response count, or 90% confidence interval is reported in the registry record. Consequently, the available information does not establish the observed response rate or its precision. The record’s stated objective and the existence of an endpoint cannot be used as evidence that a response occurred or that the treatment had a particular level of antitumor activity.

The safety counts and listed serious adverse event terms offer descriptive information about events recorded across the cohorts. They are not randomized comparative estimates, and the cohort differences in disease and treatment context limit direct comparisons. The record does not provide enough information to assign causality to the listed events or deaths.

The trial’s non-randomized, open-label design is important when considering any potential comparisons. Cohorts were defined by disease characteristics and treatment history, not by random allocation. Even if cohort outcome estimates were available, differences between cohorts could reflect their distinct populations as well as treatment-related factors. The record does not report a formal causal comparison.

In short, the available record supports a description of the design, the endpoint definition, and selected safety counts. It does not support a numerical conclusion about the primary efficacy endpoint, a comparison with standard care, or a conclusion about treatment effect. The reason for termination and the study’s own sample-size justification are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why the presence of a clearly defined endpoint is not the same as having a reportable result. ORR is defined with specific response criteria and a specified observation timeframe, but the registry record does not give the response estimate or its confidence interval. For statistical readers, separating endpoint specification from endpoint findings is essential: without the numerator and analysis denominator, the primary outcome cannot be interpreted.

It also highlights the role of design in shaping what comparisons can be made. The four cohorts addressed different clinical populations, and assignment was non-randomized. A pooled summary across those cohorts could conceal meaningful differences in disease type, PD-L1 status, treatment line, and eligibility context. A comparison between cohorts would not be equivalent to a randomized treatment comparison.

The registry includes descriptive safety counts and selected event terms, but those figures answer a different question from the primary efficacy endpoint. They need their cohort denominators and cannot establish relative risk against a control treatment that was not part of a randomized comparison. Likewise, deaths listed by cohort should not be interpreted as treatment-caused without supporting attribution information.

Finally, the record’s missing analysis details matter for transparency. It does not report the primary endpoint calculation method, missing-data handling, multiplicity strategy, or sample-size justification. These are not reasons to assume a particular analysis; they mark boundaries on what can be evaluated. The distinction between reported details and unreported methods is part of sound interpretation of clinical trial records.

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 primary limitation for interpretation is that the registry record defines ORR but does not report its estimate, response count, or 90% confidence interval. Although the primary endpoint is specified for cohorts A1 and A2, the efficacy-population size is also not reported. Without those items, neither the endpoint magnitude nor its precision can be assessed.

The design was non-randomized and open-label, with cohorts defined by different disease and treatment characteristics. The cohorts are not a like-for-like control comparison, and no randomized comparator is reported. Differences in outcomes across cohorts, if available, would not on their own isolate a treatment effect. The registry record does not report adjusted comparative analyses.

The record lists enrollment as 106 and status as terminated, but does not report why the study was terminated or whether the reason affected outcome collection. The reported primary completion date is 2023-07-18; data cut-off details are not reported in the registry record. The reason for termination, analysis timing, and any implications for completeness therefore remain unclear.

Other specific limitations include the absence of reported methods for confidence-interval calculation, missing-data handling, multiplicity control, interim analyses, and the primary endpoint analysis. The record also does not report the trial’s sample-size justification. Safety counts and event percentages are descriptive, and the available record does not provide causal attribution for deaths or a randomized safety comparison. These gaps limit the conclusions that can be drawn from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202) — NCT04914897.
• Registry record last updated 2025-10-02; status last verified 2025-09.
• Results first posted 2025-10-02.
• 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

NCT04914897 is a phase 2, non-randomized, open-label, multi-cohort, multi-center study of SAR444245 combined with other anticancer therapies in participants with NSCLC or pleural mesothelioma. The registry lists 106 participants enrolled, a start date of 2021-09-23, a primary completion date of 2023-07-18, and a terminated status.

The primary endpoint was ORR in cohorts A1 and A2, defined using confirmed complete or partial response under RECIST version 1.1, with a 90% confidence interval specified. The registry record does not report the primary endpoint result. Descriptive safety counts and selected serious adverse event terms are listed, but the study does not provide a randomized control comparison. The record does not report the reason for termination or several analysis details, including missing-data and multiplicity methods.