A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204): 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 HNSCC (Master Protocol) (Pegathor Head and Neck 204) (NCT05061420), a non-randomized phase 2 study. The primary outcome is Cohort A1: 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. Its master-protocol structure allowed investigation of SAR444245 with different partner therapies in distinct HNSCC populations. The registry record lists 59 participants enrolled and identifies Sanofi as the sponsor. The recorded start date was 2021-10-08, the primary completion date was 2023-07-21, and the study status is terminated. The reason for termination is not reported in the registry record.

The three described cohorts addressed different clinical contexts. Cohort A1 enrolled participants who were treatment-naïve for R/M disease and had a PD-L1 CPS ≥1; its combination was pembrolizumab with SAR444245. Cohort B1 involved participants previously treated with a PD1/PD-L1-based regimen and a platinum-based regimen, with pembrolizumab as the partner. Cohort B2 involved participants previously treated with a platinum-based regimen who were cetuximab-naïve, with cetuximab as the partner. The brief summary describes the B1 and B2 proof-of-concept aims as an increase in the observed number of objective responses in their respective populations.

For A1, both drugs were described as intravenous infusions on Day 1 of each 21-day cycle for up to 35 cycles. The B1 description says both drugs were given by intravenous infusion on Day 1 of each 21-day cycle for up to 35 cycles, but its final wording is truncated. The B2 description states that cetuximab was given intravenously on days 1, 8, and 15 of each 21-day cycle; the description of SAR444245 administration is incomplete. The registry record does not report random allocation, masking, or a like-for-like control arm. Because both allocation and masking were absent, the study is not a randomized blinded comparison.

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. Cohort A2 was 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 included 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 included 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 Cohort A1: Objective Response Rate (ORR), measured over From first dose of study treatment administration (Day 1) up to approximately 21 months.

The primary endpoint was Cohort A1 objective response rate (ORR), expressed as the percentage of participants with a confirmed complete response (CR) or partial response (PR) under RECIST version 1.1. A CR was defined as disappearance of all target lesions, with pathological lymph nodes reduced to a short axis <10 mm (<1 cm). A PR was defined as at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference.

ORR is a binary participant-level outcome: each participant either meets the response definition or does not. In general, this type of endpoint provides a direct summary of the proportion meeting a prespecified tumor-response criterion. It does not, by itself, describe how long a response lasts, whether disease progresses later, or how participants fare on other outcomes. The registry lists duration of response and progression-free survival among secondary outcomes.

The endpoint timeframe was 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 those who permanently discontinued study treatment. The registry record specifies a 90% confidence interval for the ORR, but does not report the observed percentage or interval limits. Thus, the endpoint definition is available, while the primary numerical result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint represent?

The primary endpoint is a percentage of participants with a binary outcome: confirmed CR or PR under RECIST version 1.1. General explanation: a binary endpoint assigns each participant to one of two outcome categories for the analysis, such as meeting or not meeting the response definition. The percentage summarizes the share in the response category, while a confidence interval describes uncertainty around that estimate.

The registry specifies a 90% confidence interval. In general, a confidence interval gives a range of values compatible with the data and the method used; it is not a guarantee that the true value lies inside the particular interval. A narrower interval generally indicates greater precision than a wider one. The interval endpoints and the response percentage are not reported in the registry record, so the precision of the A1 estimate cannot be assessed.

What does the population definition imply?

The efficacy population included exposed participants with at least one evaluable post-baseline tumor assessment or those who permanently discontinued study treatment. This is the population definition stated for the endpoint. It is not described as an analysis of every enrolled participant regardless of exposure or assessment. The record does not give the number included in the efficacy population or specify how participants with no evaluable post-baseline assessment, missing assessments, or other incomplete outcome information were handled.

General explanation: the population used for an analysis matters because the estimate applies to the participants included under that definition. If participants with missing outcome data differ from those with measured outcomes, the observed percentage may not represent the outcome pattern in the full enrolled group. Whether that concern arose in this study, and what methods were used to address it, are not reported in the registry record.

Why does the non-randomized design matter?

Allocation was non-randomized and masking was absent. General explanation: random allocation is commonly used to balance known and unknown participant characteristics between comparison groups, while masking can reduce the influence of expectations on assessments or reporting. Neither feature was present according to the registry record. The cohorts also had different treatment histories and partner drugs, so direct comparisons across them would be confounded by their distinct populations and treatment contexts. The registry record does not report a randomized control group or a statistical adjustment plan for between-cohort comparisons.

Open-label means treatment assignment was not masked. For a tumor-response endpoint, the response criteria are defined, but the record does not describe independent review, assessor masking, or other procedures for reducing assessment influence. These procedures are not reported in the registry record and should not be assumed.

What can the planning assumptions tell readers?

The sample-size illustrations are described as planning illustrations computed from the observed effect, not as the trial’s own design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations give the total number of events using the Schoenfeld method; for other outcomes, they give participants per arm.

General explanation: a planning illustration estimates the sample size or number of events that would be associated with a chosen effect and assumptions. It does not show the power actually achieved by a completed study. Such calculations also do not replace the observed estimate and its uncertainty. No calculated sample-size values or observed-effect value are reported in the registry record, and the illustrations are explicitly not the trial’s own design justification.

What does the record say about analysis procedures?

The registry lists 10 outcome measures and zero analyses. That entry does not supply analysis-level results for the primary endpoint. The record states that the primary endpoint uses a 90% confidence interval, but does not report the method used to calculate it, any hypothesis test, a significance threshold for the endpoint, or a model specification. The sample-size illustration assumptions do not establish which analysis methods were used for the trial results.

General explanation: statistical methods should match the endpoint and study design. A confidence interval for a percentage is intended to communicate uncertainty in a proportion, but its exact construction can vary. For clustered, repeated, or time-to-event data, different analysis considerations may apply. The registry identifies secondary outcomes including time to response, duration of response, clinical benefit rate, progression-free survival, plasma concentration of pegenzileukin, treatment-emergent adverse events, and anti-drug antibodies. Detailed methods for these outcomes 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("CohortA1:R/M HNSCC Treatment-naïve for R/M Disease")
n      <- c(20)
events <- c(5)
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  CohortA1:R/M HNSCC Treatment-naïve for R/M Disease  20  5  25.0  8.7  49.1  11.2  46.9  11.3  47.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the A1 primary ORR and secondary outcomes spanning safety, response timing and duration, clinical benefit, progression-free survival, plasma concentration, and anti-drug antibodies. The master protocol also describes proof-of-concept aims in multiple cohorts. Considering several outcomes or cohorts can raise multiplicity questions: in general, repeated testing can increase the chance of at least one apparently notable result if each test is interpreted without regard to the others. The registry record does not report a multiplicity adjustment, a testing hierarchy, or another strategy for controlling interpretation across outcomes and cohorts.

The record lists zero analyses and does not give a primary ORR result, a p-value, or the confidence interval limits. It therefore does not support reconstruction of a testing sequence or assessment of how multiple outcomes were handled. Whether a detailed statistical analysis plan specified such procedures is not reported in the registry record.

The primary efficacy population is defined as exposed participants with at least one evaluable post-baseline tumor assessment or those who permanently discontinued study treatment. The record does not state the number meeting that definition. It also does not report the amount or pattern of missing tumor assessments, reasons for missing data, imputation procedures, sensitivity analyses, or how participants who did not meet the efficacy-population definition were treated in the analysis. General explanation: missing outcome data can affect an estimate if the availability of measurements is related to the outcome; the direction and extent of any effect depend on the missingness pattern and analytical approach. Those details are not available in the registry record, so the effect of missing data cannot be evaluated.

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 (25.0%), cardiac arrest (10.5%), cardio-respiratory arrest (10.0%), catheter site infection (5.3%), pneumonia (5.3%).

The registry lists serious adverse event entries by cohort: 11 affected participants among 20 at risk in Cohort A1, 11 among 20 in Cohort B1, and 8 among 19 in Cohort B2. The corresponding entries for other adverse events are 20 among 20, 18 among 20, and 19 among 19. The record also lists deaths of 8, 13, and 10 in those cohorts, respectively. These are descriptive counts, not a randomized comparison. The registry record does not specify the cause of death or establish that deaths or adverse events were caused by study treatment.

The listed serious-event terms and percentages are Cytokine Release Syndrome, 25.0%; Cardiac Arrest, 10.5%; Cardio-Respiratory Arrest, 10.0%; Catheter Site Infection, 5.3%; Pneumonia, 5.3%; and Dehydration, 5.3%. The record does not identify a cohort-specific denominator for these percentages in the listed terms. They should not be interpreted as treatment-attributable rates or compared across cohorts without additional information. The registry lists treatment-emergent adverse events and serious adverse events among the outcomes, but the posted entries do not provide a complete clinical interpretation of safety.

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

The registry record establishes that a phase 2, non-randomized, open-label, multi-cohort study of SAR444245 combinations was conducted in participants with HNSCC, with total enrollment of 59 and status recorded as terminated. It describes treatment contexts, the primary A1 endpoint, and several secondary outcomes. For A1, response was defined using confirmed CR or PR under RECIST version 1.1, and the record specifies a 90% confidence interval.

What is not established by the posted results is the observed A1 ORR, the number of responders, or the interval around the estimate. The record therefore does not show how frequently participants met the response definition or how precisely that frequency was estimated. The stated aims for B1 and B2 are objectives, not findings. Without reported response estimates, the proof-of-concept aims cannot be judged from this record.

The design does not permit a randomized treatment comparison. Participants were assigned to non-randomized cohorts with different prior-treatment histories and different partner therapies. Any descriptive outcome in one cohort would not, on its own, demonstrate that a treatment caused the outcome or that it performed better than another regimen. A comparison across these cohorts would not be like-for-like.

Safety entries describe affected participants, listed serious-event terms, and deaths. The record does not establish treatment causality for these events, identify the cause of death, or provide sufficient detail to infer comparative safety. More broadly, the absence of analysis results, missing-data details, and multiplicity procedures leaves important questions about statistical interpretation unanswered. The registry information is useful for understanding the study structure and endpoint definitions, but it does not provide the primary numerical efficacy result or enough analysis detail to determine its robustness.

14. Why This Trial Matters Statistically

This study illustrates why a master protocol should be read as a structure for related but distinct investigations, not as one uniform treatment comparison. A1, B1, and B2 had different prior-treatment contexts and partner drugs. Their clinical questions and populations therefore need to remain distinct when interpreting outcomes. The non-randomized design is central to that interpretation: cohort results can be descriptive, but they do not provide a randomized estimate of comparative treatment effect.

It also demonstrates the distinction between a clearly defined endpoint and a reported endpoint result. The registry gives a detailed ORR definition, a timeframe, and an efficacy-population definition for Cohort A1. Yet it does not report the observed response percentage or its 90% confidence interval. A prespecified-looking definition cannot substitute for the estimate needed to assess the frequency and precision of response.

Finally, the registry record highlights the importance of analysis transparency. It lists multiple outcomes and cohort aims, while multiplicity procedures, detailed missing-data handling, and analysis methods are not reported. Safety entries are available, but their causal interpretation and cohort-specific detail are limited. For biostatisticians and clinical researchers, the key statistical lesson is to distinguish protocol aims, endpoint definitions, descriptive counts, and inferential results. Each answers a different question, and the posted record contains the first three more clearly than the last.

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 registry record has several limitations specific to interpretation of this study. Most importantly, it does not report the primary Cohort A1 ORR, the responder count, or the 90% confidence interval, despite defining the endpoint. It also lists zero analyses, so no analysis-level result is available to clarify the primary question. The reason for the terminated status is not reported in the registry record.

The study was non-randomized and open-label. There is no like-for-like control comparison in the posted design, and the cohorts differ in prior treatment and partner therapy. Consequently, the record cannot support a randomized comparison across treatments or a causal interpretation based solely on cohort outcomes. The registry does not report masking of response assessment or procedures such as independent review.

Important analysis details are absent: the efficacy-population size, handling of missing assessments, sensitivity analyses, detailed statistical methods, and multiplicity procedures are not reported. The listed safety counts and death counts do not establish treatment attribution or cause of death. The record also does not provide cohort-specific denominators for the listed serious-event percentages.

Some treatment descriptions are incomplete. The B1 regimen description ends mid-word, and the B2 description of SAR444245 administration is truncated. In addition, the B1 arm description names SAR444244, whereas the intervention list and other descriptions identify SAR444245. The registry record does not resolve this discrepancy. These limitations constrain interpretation of treatment details as well as efficacy and safety.

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 HNSCC (Master Protocol) (Pegathor Head and Neck 204) — NCT05061420.
• Registry record last updated 2025-09-22; status last verified 2025-08.
• Results first posted 2025-09-22.
• 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

NCT05061420 is a phase 2, non-randomized, open-label, multi-cohort, multi-center study of SAR444245 combined with pembrolizumab or cetuximab for participants with HNSCC. The record lists enrollment of 59, sponsor Sanofi, a start date of 2021-10-08, primary completion on 2023-07-21, and status terminated.

The primary endpoint was Cohort A1 ORR, defined by confirmed CR or PR under RECIST version 1.1, with a 90% confidence interval and a timeframe from first dose up to approximately 21 months. The observed ORR and interval are not reported in the registry record. Descriptive safety counts are listed for A1, B1, and B2, but do not establish treatment causality. The record also does not report the reason for termination, detailed analysis methods, missing-data handling, or multiplicity procedures.