This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for BEMPEG With Pembrolizumab vs Pembrolizumab Alone in Patients With Metastatic or Recurrent HNSCC (PROPEL-36) (NCT04969861), a randomized phase 2, phase 3 study. The primary outcome is Overall Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04969861 |
| Phase | Phase 2, Phase 3 |
| Condition | Metastatic Head and Neck Cancer, Recurrent Head and Neck Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Nektar Therapeutics |
| Results posted | Yes |
2. Clinical Question
Population
Patients with recurrent or metastatic head and neck squamous-cell carcinoma and PD-L1-expressing tumors, with the study summary specifying positive expression at CPS ≥ 1. The study is described as first-line treatment.
Intervention
Bempegaldesleukin combined with pembrolizumab, administered every 3 weeks for up to 35 cycles, approximately 2 years.
Comparator
Pembrolizumab monotherapy, administered every 3 weeks for up to 35 cycles, approximately 2 years.
Primary question
Whether overall survival differs between the combination regimen and pembrolizumab monotherapy in this study population. The registry record gives the endpoint name and an approximate timeframe, but reports no outcome comparison.
PROPEL-36 was designed to compare the efficacy and safety of the combination with pembrolizumab alone. Its primary endpoint is overall survival. The registry also names progression-free survival, time to deterioration, change in global health status or quality of life, and treatment-emergent adverse events and serious adverse events among the secondary outcomes. The outcome record does not give numerical results for the primary endpoint or an analysis comparing the treatment groups.
The registry record lists the study as terminated and gives enrollment as 1. It does not report why the study was terminated or describe how enrollment was distributed between the treatment groups. Consequently, the stated clinical question is the study's intended comparison, not a conclusion about which regimen performed better. The available record does not establish an effect on survival, quality of life, or safety.
3. Trial Design
PROPEL-36 is described as a multicenter, randomized, open-label Phase 2/3 study with a parallel-group design. Participants were to be assigned to bempegaldesleukin plus pembrolizumab or pembrolizumab monotherapy. The record identifies no masking. These features describe the planned comparison; the available record does not provide details of the randomization procedure, allocation concealment, or operational conduct at study sites.
The combination arm is described as receiving bempegaldesleukin plus pembrolizumab every 3 weeks for up to 35 cycles, approximately 2 years. The comparator arm is described as receiving pembrolizumab alone on the same schedule and for the same maximum duration. Whether treatment actually continued for the planned duration, and how treatment discontinuation was handled, are not reported in the registry record.
The listed study start date is 2022-03-09, and the primary completion date is 2022-04-22. The study status is terminated. The registry lists enrollment as 1. These entries do not establish how many participants were randomized, treated, or included in any particular outcome analysis. The reason for termination, the number assigned to each arm, and the timing and circumstances of any termination decision are not reported in the registry record.
The registry identifies overall survival as the primary outcome, with an approximate timeframe of 2 years. It lists six outcome measures and names progression-free survival, time to deterioration, change in global health status or quality of life, and treatment-emergent adverse events and serious adverse events as secondary outcomes. Detailed assessment schedules, endpoint definitions beyond the titles, and analysis populations are not reported. No analysis entries are listed, so the record does not show a completed statistical comparison of the planned treatment groups.
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
| Stage | BEMPEG + Pembrolizumab | Pembrolizumab Monotherapy |
|---|---|---|
| STARTED | 1 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | BEMPEG + Pembrolizumab | Pembrolizumab Monotherapy |
|---|---|---|
| Study was terminated in consonance with discontinuation of bempegaldesleukin program. | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Nektar and BMS Study PIVOT-IO-001 did not meet its primary EP of demonstrating an efficacy advantage from addition of BEMPEG to nivolumab in patients with previously untreated inoperable or metastatic melanoma. PIVOT-09 (RCC) and PIVOT-10 (uroth C) studies also reported negative topline results. Based on these 3 large negative studies, Nektar and SFJ in consultation with the study IDMC made the decision to discontinue this trial. At termination, 1 patient was enrolled and treated for 2 cycles.
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: Following the Sponsor's decision to end the trial, treatment was discontinued after one patient received 2 cycles of BEMPEG + Pembrolizumab
| Characteristic | Unit | BEMPEG + Pembrolizumab | Pembrolizumab Monotherapy | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 0 | 1 | |
| Age, Categorical: <=18 years | Participants | 0 | — | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | — | 0 |
| Age, Categorical: >=65 years | Participants | 1 | — | 1 |
| Age, Continuous | years | 69 (69 to 69) | — | 69 (69 to 69) |
| Sex: Female, Male: Female | Participants | 0 | — | 0 |
| Sex: Female, Male: Male | Participants | 1 | — | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | — | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | — | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | — | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | — | 0 |
| Race (NIH/OMB): White | Participants | 1 | — | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 | — | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | — | 0 |
| Region of Enrollment: Austria | participants | 0 | — | 0 |
| Region of Enrollment: Greece | participants | 0 | — | 0 |
| Region of Enrollment: United States | participants | 1 | — | 1 |
| Region of Enrollment: Italy | participants | 0 | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival, measured over Approximately 2 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
Overall survival is the primary endpoint. As a general statistical concept, overall survival is a time-to-event measure: it records the time from a defined starting point until death. In many studies, death from any cause is used as the event, but the precise event definition and the time origin for PROPEL-36 are not reported in the registry record. The stated timeframe is approximately 2 years.
Time-to-event endpoints are useful when the timing of an event matters and participants may have different lengths of follow-up. They can incorporate information from participants whose event has not been observed by the end of their available follow-up, provided the analysis handles censoring appropriately. Censoring means that the event time is not observed within the available follow-up; it does not mean that the event never occurs.
Overall survival is a direct measure of survival time, but interpreting a treatment comparison requires more than the endpoint name. The analysis needs a defined time origin, adequate follow-up, an approach to censoring, and a specified summary measure or comparison method. Those details and any estimated treatment effect are not reported in the registry record. The endpoint title and timeframe alone therefore do not indicate whether survival differed between the treatment groups or how precisely any difference was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a planned comparison of bempegaldesleukin plus pembrolizumab with pembrolizumab alone, but it does not report an overall-survival estimate or a statistical test for that comparison. No effect size, confidence interval, or p-value for the primary endpoint is available in the record. As a result, the posted information cannot quantify the direction, size, or precision of an overall-survival difference.
The record lists six outcome measures and names several secondary outcomes, but it contains no analysis entries. A list of intended outcomes is not the same as an analysis result: it does not show what was observed, how groups compared, or whether an estimate was adjusted. The primary outcome description includes contextual text about other studies, but that text is not a result for PROPEL-36 and cannot answer its primary question.
The registry status is terminated, and the enrollment field is 1. These details are important context for interpreting the record, but they do not explain why the study ended, establish the number randomized or analyzed, or show that a treatment effect was absent. The reason for termination and the disposition of participants are not reported in the registry record. No conclusion about efficacy should be inferred from termination alone.
The adverse-event entries are also limited. They report counts of participants at risk and affected for the listed categories, along with deaths, but they do not provide a comparative statistical analysis. With such limited recorded counts, the entries cannot characterize the range or frequency of potential harms in a broader population. The registry lists no serious adverse-event terms.
Any sample-size figures presented as planning illustrations should be read as hypothetical design calculations based on the stated assumptions, not as observed power or evidence that the trial could detect a particular effect. The registry record does not provide a reported treatment-effect estimate on which to base an independent interpretation. Recalculated comparisons cannot replace a sponsor analysis; if a discrepancy is identified, the sponsor's own analysis takes precedence. No such primary-outcome analysis is listed in this record.
The appropriate statistical conclusion is therefore limited: the registry describes the intended design and outcomes, but does not report results that resolve the survival comparison. This is different from evidence that the regimens are equivalent or that either regimen is superior. The available record leaves the treatment effect and its uncertainty undetermined.
9. Statistical Methods Explained
What can be learned from a randomized parallel-group design?
As a general statistical point, random assignment aims to make treatment groups comparable at the start of a study with respect to both measured and unmeasured characteristics. A parallel-group design follows participants in their assigned groups rather than having each participant receive both regimens. Randomization can support a causal interpretation when the trial is conducted and analyzed appropriately, but the design label by itself does not ensure that the resulting comparison is unbiased. Details of the randomization method, allocation concealment, adherence, and analysis population are not reported in the registry record.
Open-label means that masking is absent. Knowledge of treatment assignment can influence care, reporting, or assessment, especially for outcomes involving judgment or self-report. Overall survival is less dependent on subjective assessment than some outcomes, but follow-up, treatment changes, and decisions about censoring still matter. The registry record does not describe procedures intended to limit these influences.
How are time-to-event outcomes generally analyzed?
As a general statistical explanation, time-to-event methods account for both whether an event occurred and how long participants were followed. Participants without an observed event may contribute follow-up information until their last known observation; this is commonly handled through censoring. Valid interpretation depends on suitable definitions and assumptions about follow-up and censoring. The registry names overall survival and an approximate timeframe, but does not report the time origin, censoring rules, follow-up distribution, or statistical method used for this endpoint.
Common general approaches include estimating survival over time and comparing groups using a time-to-event test or a model for relative event rates. A hazard ratio, if used, would describe a relative rate over follow-up under the model's assumptions; it would not directly state how much longer an individual lives. A survival probability at a specified time would answer a different question. The registry record gives none of these estimates or methods, so none should be attributed to PROPEL-36.
What does a confidence interval contribute?
In general, a confidence interval expresses the statistical uncertainty around an estimated effect under a specified method. A narrow interval indicates greater precision than a wide interval, while an interval that includes values compatible with no difference may leave the direction or size of an effect uncertain. Interpretation requires attention to the interval's scale, the analysis assumptions, and the clinical question. No confidence interval for the primary comparison is reported in the registry record.
A p-value, as a general concept, measures how incompatible the observed data are with a specified null model, under the assumptions of the test. It does not measure the probability that a treatment works, nor does it convey the size or practical importance of an effect. A p-value cannot compensate for missing estimates or incomplete reporting. No primary-outcome p-value is listed in the registry record.
What do the planning calculations mean?
The stated planning illustrations use a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. They describe effects as fractions of an observed effect. For time-to-event calculations, the stated approach gives the total number of events using Schoenfeld; other calculations are described as participants per arm. These are planning assumptions, not observed results. A planned sample size or event target is not evidence about what the study actually enrolled or observed, and a planning calculation must not be described as observed power.
For any planning illustration, the assumed effect is central: changing the effect to be detected changes the implied sample-size requirement. A calculation based on a fraction of an observed effect is only an illustration under its assumptions and does not establish that the underlying effect is reliable. The registry record does not report the numerical effect estimate or planning figures in the outcome information summarized for this trial, and it does not report the trial's own sample-size justification.
Why can over-dispersion matter?
As a general statistical point, over-dispersion occurs when variability in the data exceeds what a chosen model assumes. If a model underestimates variability, uncertainty intervals can be too narrow and tests can appear more decisive than warranted. Appropriate methods depend on the outcome type and data structure. The registry record does not report evidence of over-dispersion or a method used to address it; this general issue should not be read as a finding about PROPEL-36.
What remains unknown about the analysis?
The registry record does not report the primary analysis model, covariate adjustment, handling of treatment changes, analysis population, missing-data approach, or any interim-analysis plan. These details can affect both the estimate and its uncertainty. Without them, and without the outcome data themselves, a reader cannot reproduce or evaluate a trial-specific analysis. The methods above explain general statistical ideas; they are not claims that PROPEL-36 used those methods.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists overall survival as the primary outcome and names progression-free survival, time to deterioration, change in global health status or quality of life, and treatment-emergent adverse events and serious adverse events among the secondary outcomes. It does not report a testing hierarchy, a multiplicity adjustment, or a procedure for deciding which comparisons would be confirmatory. When several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. As a general approach, studies may define a hierarchy or adjust testing, but the strategy used for this trial is not reported in the registry record.
The record lists six outcome measures, but only the named outcomes and the primary overall-survival timeframe are described in the available information. Further outcome definitions, assessment timing, and analysis details are not reported in the registry record. No analysis entries are listed. Accordingly, there are no reported outcome estimates with which to assess multiplicity in practice.
The registry record does not describe missing-data rules, censoring rules, reasons for missing assessments, or sensitivity analyses. Missingness can affect interpretation when participants with unavailable measurements differ from those with observed measurements. For a time-to-event endpoint, incomplete follow-up and censoring also need explicit consideration. These are general methodological concerns, not evidence that a particular missing-data problem occurred in PROPEL-36.
Analysis populations are not specified in the available record. It is therefore not possible to determine whether the intended analysis followed randomized assignment, included participants who received treatment, or used another defined population. The enrollment entry and adverse-event counts do not establish the composition of an efficacy analysis set.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BEMPEG + Pembrolizumab | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BEMPEG + Pembrolizumab | 0 of 1 |
| Pembrolizumab Monotherapy | 0 of 0 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BEMPEG + Pembrolizumab | 1 of 1 |
| Pembrolizumab Monotherapy | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BEMPEG + Pembrolizumab | Pembrolizumab Monotherapy |
|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 1 | n/a of 0 |
The registry's serious adverse-event entries list the BEMPEG plus pembrolizumab group as having 1 participant at risk and 0 affected; the pembrolizumab monotherapy group is listed with 0 at risk and 0 affected. Deaths are listed as 0 in both groups. No serious adverse-event terms are listed.
These are registry counts, not a detailed safety comparison. The record does not report event descriptions, timing, duration, severity grading, relatedness, exposure time, or a statistical comparison. A count of 0 affected in a group does not establish that a regimen has no serious risks, and a group listed with 0 at risk cannot support a meaningful comparison with another group. The enrollment entry is 1, but the record does not explain how these counts relate to participant assignment or follow-up.
For other adverse events, the BEMPEG plus pembrolizumab group is listed with 1 at risk and 1 affected, while the monotherapy group is listed with 0 at risk and 0 affected. These entries do not identify the event or support a rate calculation for a broader population. The record does not report enough detail to compare safety between regimens or to characterize the types of events observed.
12. What the Result Does, and Does Not, Mean
The registry record identifies an important intended comparison: bempegaldesleukin plus pembrolizumab versus pembrolizumab alone for first-line treatment of recurrent or metastatic head and neck squamous-cell carcinoma with PD-L1-expressing tumors. It specifies overall survival as the primary endpoint and lists several secondary outcomes. That information describes what the study set out to assess; it is not evidence of the result.
No numerical result for overall survival, treatment effect, confidence interval, or statistical test is reported. No analysis entries are listed. Consequently, the registry record does not establish that either regimen improved survival, worsened survival, or had outcomes equivalent to the other. An absent estimate is not an estimate of no effect. It leaves the comparison unresolved in the posted information.
The record's terminated status should also be interpreted narrowly. It indicates the recorded study status, but the reason for termination is not reported in the registry record. It does not, on its own, show whether termination was related to efficacy, safety, recruitment, operational considerations, or another cause. The entry for enrollment and the limited adverse-event counts do not fill that gap.
Statistically, the missing effect estimate matters because readers cannot judge either magnitude or precision. A point estimate would describe the observed comparison, while an interval would convey uncertainty under the analysis method. Without these, neither the size of a possible effect nor the range of values compatible with the data can be assessed. The record also does not supply the analysis methods needed to evaluate assumptions or robustness.
The appropriate interpretation is that the available registry information documents the planned design and selected outcome entries but does not provide a usable result for the primary clinical question. It should not be treated as evidence for or against either regimen. Any planning illustration is hypothetical and should not be confused with observed efficacy or observed power.
13. Why This Trial Matters Statistically
PROPEL-36 is statistically notable as a randomized, open-label Phase 2/3 comparison with overall survival named as its primary outcome. The combination and monotherapy arms were described with the same dosing interval and maximum treatment duration, allowing the intended question to focus on adding bempegaldesleukin to pembrolizumab. The registry also identifies secondary outcomes that span disease progression, time to deterioration, quality of life, and adverse events.
At the same time, the record illustrates the distinction between a trial's design and its evidentiary contribution. A randomized design can define a comparative question, but a clinical interpretation depends on reporting enrollment, follow-up, outcome events, estimates, uncertainty, and analysis methods. In this record, the status is terminated, enrollment is listed as 1, and no analysis entries are listed. The reason for termination and the primary endpoint result are not reported.
This gap is statistically consequential. Without an effect estimate and its precision, readers cannot judge how compatible the observed data are with different treatment effects. Without analysis details, readers cannot evaluate assumptions about censoring, analysis populations, missing data, or multiplicity. A record that describes an intended comparison but lacks its analysis cannot establish either a positive finding or a null finding.
The case also underscores why safety counts require context. Counts with very limited recorded numbers and no event descriptions or exposure information cannot support a broad safety comparison. Complete and clearly defined outcome reporting is needed to distinguish a meaningful comparative result from a sparse or uninterpretable record.
14. 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 principal limitation is that the registry record does not report a primary overall-survival analysis. It gives the endpoint title and an approximate timeframe, but no event count, estimated effect, confidence interval, p-value, or analysis method. The record therefore cannot answer the trial's primary comparative question.
The study is listed as terminated, with enrollment of 1. The reason for termination, recruitment history, participant disposition, arm allocation, treatment exposure, and follow-up are not reported in the registry record. The listed enrollment cannot be assumed to represent the number randomized, treated, or included in an outcome analysis.
Outcome reporting is incomplete for statistical interpretation. The record lists six outcome measures but gives limited detail on the named secondary outcomes, and it contains no analysis entries. The time origin, event definitions, assessment schedules, censoring rules, analysis populations, missing-data approach, covariate adjustment, and multiplicity strategy are not reported. These omissions prevent evaluation of the planned analysis and its assumptions.
The safety entries are also sparse. They provide counts at risk and affected for the listed adverse-event categories, but do not give event terms for serious adverse events or describe event type, severity, relatedness, timing, or exposure. The recorded counts do not allow a reliable comparative safety interpretation.
Finally, the primary outcome description includes contextual text about other studies rather than a PROPEL-36 result. That material does not substitute for a trial-specific outcome analysis. The record does not explain whether results were unavailable, uncollected, or not entered, so no explanation should be inferred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BEMPEG With Pembrolizumab vs Pembrolizumab Alone in Patients With Metastatic or Recurrent HNSCC (PROPEL-36) — NCT04969861.
- Registry record last updated 2023-01-12; status last verified 2022-11.
- Results first posted 2022-12-15.
- 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.
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18. Record Summary
PROPEL-36 is a randomized, open-label, parallel-group Phase 2/3 study of bempegaldesleukin plus pembrolizumab versus pembrolizumab alone for first-line treatment of recurrent or metastatic head and neck squamous-cell carcinoma with PD-L1-expressing tumors. Both regimens were described as being given every 3 weeks for up to 35 cycles, approximately 2 years.
The registry lists overall survival as the primary outcome, with an approximate timeframe of 2 years, and names several secondary outcomes. Study status is terminated; the registry lists enrollment as 1. No analysis entries or primary-outcome comparison are reported. The reason for termination, participant allocation, analysis methods, and treatment effect are not reported in the registry record. The available information describes the intended study question but does not resolve it.