A Study of Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma (NCT05909904), a randomized phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The central statistical question is whether the observed response proportions in the combination groups differ from the proportion in the tislelizumab-alone group, and how precisely those differences are estimated. The registry reports response rates and 95% confidence intervals for each group, alongside sponsor-reported risk differences. Recalculations from the posted group summaries give unadjusted comparisons, but they do not replace the sponsor's analysis.

The study was randomized and parallel-group, with no masking. The record identifies four treatment groups, each with 40 participants in the primary endpoint data. The findings therefore describe the posted outcomes in these groups; they do not by themselves establish that any observed difference is attributable to adding an investigational agent. The confidence intervals and the limited size of each group are important when judging how much the estimates can distinguish between treatment approaches.

3. Trial Design

This was a randomized, phase 2, open-label, parallel-group study. Its official title describes first-line treatment with tislelizumab in combination with investigational agents for recurrent or metastatic head and neck squamous cell carcinoma. The registry lists an enrollment of 160 and a completed study status. The primary completion date is 2025-06-17.

Four groups are represented in the posted primary outcome: tislelizumab alone; tislelizumab plus surzebiclimab; tislelizumab plus alcestobart; and tislelizumab plus both surzebiclimab and alcestobart. Each group has 40 participants in the primary endpoint results. The study is described as randomized, but the registry record does not report the randomization method or allocation ratio as a protocol detail. The arm results are consistent with equal group sizes, but that does not establish what procedures were specified for randomization.

The arm descriptions state that treatments were given by intravenous infusion on Day 1 of each 21-day cycle. The descriptions say treatment could continue for up to 2 years, subject to disease progression, intolerable toxicity, withdrawal of informed consent, or another discontinuation criterion. The study was open-label, so masking of participants or investigators was not used.

The primary endpoint was investigator-assessed objective response rate (ORR), defined by confirmed complete or partial response under RECIST v1.1. The timeframe is up to 21.2 months, and the analysis population is the Intent-to-Treat Analysis Set, defined as all randomized participants. The registry also lists progression-free survival, duration of response, clinical benefit rate, disease control rate, treatment-emergent adverse events, and overall survival among the secondary outcomes. The registry record does not report a detailed statistical analysis plan or sample-size justification.

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: Eligible participants were randomized in a 1:1 ratio into the four treatment groups. Randomization was stratified based on programmed cell death protein ligand-1 (PD-L1) expression.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Analysis Set: all randomized participants.

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.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over Up to 21.2 months.

The primary endpoint, objective response rate, is the percentage of participants with a confirmed complete response or confirmed partial response, assessed by investigators using RECIST v1.1. A complete response requires disappearance of target and nontarget lesions, normalization of tumor marker level, and no new lesions. A partial response requires at least a 30% decrease in the sum of diameters of target lesions, without unequivocal progression of nontarget lesions or new lesions.

ORR is a binary outcome at the participant level: a participant either meets the response definition or does not. Reporting the percentage makes the result easy to interpret as the proportion of participants meeting the endpoint. The registry gives a 95% confidence interval for each group, which communicates uncertainty around each estimated response proportion. Because response is assessed using specified imaging criteria, this endpoint captures tumor shrinkage meeting those criteria; it does not, on its own, describe how long a response lasts or whether participants live longer.

The endpoint is assessed up to 21.2 months. That timeframe is part of the reported endpoint definition and matters when interpreting the proportion: the result concerns confirmed responses recorded within that assessment window, not an unlimited follow-up period. The registry identifies the analysis population as all randomized participants. This population definition is relevant because it anchors the reported percentages to randomization rather than only to participants who completed treatment or had a particular post-randomization experience.

ORR is one measure among several listed in the registry. The listed secondary outcomes include duration of response and time-to-event outcomes, which address different questions from whether a confirmed response occurred. The primary response result should therefore be interpreted as a measure of observed response frequency, not as a complete account of disease course or safety.

7. Results Posted in the Registry

• Tislelizumab + Surzebiclimab: 27.5% (11/40) versus 27.5% (11/40) on control; risk difference 0.0 percentage points (95% CI -19.6 to 19.6), risk ratio 1.00 (0.49–2.04); unadjusted two-proportion z-test p = 1.000.
• Tislelizumab + Alcestobart: 25.0% (10/40) versus 27.5% (11/40) on control; risk difference -2.5 percentage points (95% CI -21.8 to 16.8), risk ratio 0.91 (0.44–1.90); unadjusted two-proportion z-test p = 0.799.
• Tislelizumab + Surzebiclimab + Alcestobart: 27.5% (11/40) versus 27.5% (11/40) on control; risk difference 0.0 percentage points (95% CI -19.6 to 19.6), risk ratio 1.00 (0.49–2.04); unadjusted two-proportion z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Clinical Benefit Rate (CBR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Tislelizumab + Surzebiclimab: 37.5% (15/40) versus 32.5% (13/40) on control; risk difference 5.0 percentage points (95% CI -15.9 to 25.9), risk ratio 1.15 (0.63–2.10); unadjusted two-proportion z-test p = 0.639.
  • Tislelizumab + Alcestobart: 35.0% (14/40) versus 32.5% (13/40) on control; risk difference 2.5 percentage points (95% CI -18.2 to 23.2), risk ratio 1.08 (0.58–1.99); unadjusted two-proportion z-test p = 0.813.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tislelizumab + Surzebiclimab and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tislelizumab + Alcestobart and the control. The interval gives the range of effects that remain compatible with the data.

Disease Control Rate (DCR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Tislelizumab + Surzebiclimab: 67.5% (27/40) versus 55.0% (22/40) on control; risk difference 12.5 percentage points (95% CI -8.7 to 33.7), risk ratio 1.23 (0.86–1.75); unadjusted two-proportion z-test p = 0.251.
  • Tislelizumab + Alcestobart: 62.5% (25/40) versus 55.0% (22/40) on control; risk difference 7.5 percentage points (95% CI -14.0 to 29.0), risk ratio 1.14 (0.79–1.64); unadjusted two-proportion z-test p = 0.496.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tislelizumab + Surzebiclimab and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tislelizumab + Alcestobart and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the questions beyond whether a confirmed response occurred. The registry lists clinical benefit rate and disease control rate as percentage outcomes, as well as progression-free survival, duration of response, overall survival, and treatment-emergent adverse events. These endpoints address different aspects of disease course and safety, so their results are not interchangeable with ORR.

Across the posted secondary percentage outcomes, the estimates have the same general limitation as the primary result: the group-level confidence intervals are broad, and the recalculated comparisons do not sharply distinguish the combination groups from tislelizumab alone. This pattern should be read as uncertainty in these estimates, not as proof that the regimens are equivalent. The detailed per-group secondary estimates and comparisons are reported with their endpoint results.

The secondary outcomes can provide context for the primary endpoint, but they do not erase its uncertainty or establish a single overall treatment effect. Response frequency, disease control, clinical benefit, time to progression, response duration, survival, and adverse events represent distinct outcomes. Their interpretation depends on their definitions, follow-up, and analysis methods.

Unadjusted secondary findings generally carry less confirmatory weight when many endpoints or comparisons are examined without a reported multiplicity procedure. The registry record does not report whether secondary testing was adjusted, whether a testing hierarchy was prespecified, or how those outcomes were handled in a formal statistical plan. The numerical results for the remaining listed secondary outcomes are not reported in the registry record. Without those details, secondary results are most useful as descriptive context and should not be treated as independent confirmation of the primary finding.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Progression-free Survival (PFS)
• Duration of Response (DOR)
• Clinical Benefit Rate (CBR)
• Disease Control Rate (DCR)
• Number of Participants With Treatment-Emergent Adverse Events
• Overall Survival (OS)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant is classified according to whether a confirmed complete or partial response occurred. A group response percentage is the proportion meeting that definition, expressed as a percentage. The registry reports the group estimates with 95% confidence intervals. Such an interval conveys the uncertainty associated with an estimate: under the statistical assumptions used to construct it, the method is designed to produce intervals that cover the underlying value at the stated rate over repeated samples. It is not a guarantee that the underlying response proportion lies within any one calculated interval.

What does the risk difference compare?

A risk difference compares the outcome proportions in two groups by subtracting one group proportion from the other. A value of zero represents no difference in the two estimated proportions. The recalculated comparisons use tislelizumab alone as the reference and are unadjusted calculations from the posted group summaries. For tislelizumab plus surzebiclimab and for the three-agent combination, the recalculated risk difference is 0.0. For tislelizumab plus alcestobart, it is -0.025. Each estimate has a 95% confidence interval that spans zero, so the intervals do not rule out no difference.

The sponsor's reported risk differences are also shown in the registry, with confidence intervals, but no p-values are listed for those sponsor-reported analyses. The recalculated p-values are unadjusted and are not evidence that an analysis was prespecified or used by the sponsor. They should be interpreted alongside the estimates and their intervals rather than as stand-alone conclusions.

How should the p-values be read?

A p-value describes how compatible the observed data are with a specified null model, assuming that model and the calculation's assumptions apply. It is not the probability that the null hypothesis is true, and it is not a measure of the size or clinical importance of an effect. The listed recalculated p-values are 1.0 for the two comparisons with an estimated risk difference of 0.0 and 0.799 for the tislelizumab plus alcestobart comparison. They are unadjusted; the registry record does not report adjusted p-values or a multiplicity procedure.

When multiple comparisons or endpoints are considered, the chance of at least one apparently notable result can increase if each is assessed without accounting for the others. This is why a set of unadjusted results generally provides weaker confirmatory evidence than a prespecified analysis that addresses multiplicity. The registry record does not report how the primary and secondary outcomes were ordered for formal hypothesis testing, or whether a hierarchy was used.

What are the planning illustrations?

The posted planning illustrations use the observed effect as a starting point and consider the stated fractions of that effect. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For these binary outcomes, the illustrations report participants per arm for 80% power and participants per arm for 90% power. They are planning illustrations, not observed power and not evidence about the trial's original design. The registry record does not report that these assumptions were the sponsor's design assumptions.

Planning estimates based on an observed effect can be unstable, particularly when that effect comes from groups with limited size. A small observed difference can imply a very large planning requirement, while a larger observed difference can imply a smaller one. The illustrations are conditional on the effect used and the statistical assumptions; they do not establish what effect would be seen in a future study. No planning illustration is listed for every primary comparison, so no missing values should be inferred.

How do the secondary outcomes fit?

The registry lists clinical benefit rate and disease control rate alongside time-to-event outcomes and treatment-emergent adverse events. Clinical benefit rate and disease control rate are also percentages of participants, while progression-free survival, duration of response, and overall survival are different outcome types. Their interpretation requires their own endpoint definitions and analysis details. The registry record does not report a detailed statistical analysis plan, including how missing outcomes, censoring, or multiplicity were handled.

These statistical methods explain how to read the posted results, but they cannot resolve unreported design choices. The primary analysis population is explicitly identified as all randomized participants. The registry record does not report additional details on missing primary outcome data, sensitivity analyses, stratification, covariate adjustment, or interim analyses. The unadjusted recalculations therefore remain limited comparisons of the displayed group summaries, rather than a reconstruction of the full analysis plan.

11. Confidence Intervals and Precision

The 95% confidence intervals for the primary group response estimates are wide relative to their point estimates. The interval is 14.6% to 43.9% for tislelizumab alone, tislelizumab plus surzebiclimab, and the three-agent combination; it is 12.7% to 41.2% for tislelizumab plus alcestobart. These ranges show that the estimates are not highly precise. The registry reports 40 participants in each group for this endpoint.

The recalculated risk-difference intervals likewise span zero and allow for differences in either direction. For the two comparisons with an estimate of 0.0, the interval is -0.196 to 0.196. For tislelizumab plus alcestobart, the interval is -0.218 to 0.168. The intervals indicate that the data do not narrowly pinpoint the size or direction of a difference. Their breadth is important: a point estimate near zero does not mean that all potentially relevant differences have been excluded.

A confidence interval describes statistical uncertainty under the method used; it does not account for every source of uncertainty. It does not correct for potential bias, unreported analytical choices, endpoint assessment issues, or the consequences of examining multiple outcomes. The registry record identifies the study as open-label and the primary assessment as investigator-assessed, but does not report additional details on independent review or sensitivity analyses.

Precision should also be distinguished from clinical importance. Statistical intervals alone do not establish what size of difference would matter to patients or clinicians, and the registry record does not report a threshold for a clinically important ORR difference. The estimates are therefore best read with their confidence intervals, the endpoint definition, the study design, and the absence of reported multiplicity and missing-data details in mind.

12. Analyses Reported by the Sponsor

The registry lists sponsor-reported risk differences for the comparisons with tislelizumab alone, together with 95% confidence intervals. The reported values are -0.6, with an interval from -19.5 to 18.3, for tislelizumab plus surzebiclimab; -3.0, with an interval from -21.9 to 15.8, for tislelizumab plus alcestobart; and 0.0, with an interval from -19.6 to 19.6, for the three-agent combination. No sponsor-reported p-values are listed for these analyses.

The simple recalculations use the posted group percentages and produce risk differences of 0.0, -0.025, and 0.0 for those same comparisons, with their own 95% confidence intervals and unadjusted p-values. These calculations are not a reconstruction of the sponsor's analysis method. The registry record does not report the method used for the sponsor-reported comparisons, so the basis for any small differences between the reported and recalculated estimates cannot be established from the record.

The registry discrepancy indicator is false. The sponsor-reported analysis and the simple recalculations should therefore be presented as distinct summaries, not treated as though they were generated by identical methods. The sponsor's reported analysis is the trial's own analysis; the recalculations are supplementary, unadjusted comparisons based on the posted summaries.

13. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is identified, but the registry record does not report a detailed statistical analysis plan describing the testing strategy across the four groups. In particular, it does not report whether the comparisons with tislelizumab alone were adjusted for multiplicity, whether a hierarchy or gatekeeping approach was prespecified, or whether any interim analyses were planned or conducted. The recalculated p-values are unadjusted, and the sponsor-reported analyses do not list p-values.

Multiplicity matters when several comparisons or outcomes are examined. Without an adjustment or a prespecified testing strategy, nominal p-values may overstate the strength of evidence if interpreted as though only one comparison had been considered. The unadjusted results should therefore be treated as descriptive comparisons rather than as definitive evidence from a family-wise testing procedure. The record does not establish that no such procedure existed; it simply does not report one.

The primary population is defined as all randomized participants. The registry record does not report the amount or handling of missing primary outcome data, whether any participants were excluded from the posted endpoint analysis, or whether sensitivity analyses were conducted. It also does not report detailed methods for handling missing assessments or other post-randomization events. These omissions make it difficult to assess the possible influence of missing data from the registry record alone.

The record lists secondary endpoints but does not provide a complete analysis plan for all of them. The numerical results for several listed outcomes are not reported in the registry record, and the record does not specify how outcome-specific analysis populations were defined. It also does not report whether adjusted analyses, stratification factors, or covariates were used for the primary comparison. These details are relevant because they affect how analyses are specified and interpreted.

These gaps do not invalidate the posted results, but they limit independent evaluation of the analysis choices. The most defensible reading is to distinguish what the registry explicitly reports from what remains unreported, and not to infer a protocol or statistical plan from the observed results.

14. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (10.3%), mouth haemorrhage (7.5%), pleural effusion (5.1%), pneumonia aspiration (5.0%), alanine aminotransferase increased (5.0%).

The registry reports serious adverse events and other adverse events by group, with the number at risk and the number affected. For serious adverse events, the listed figures are 17 of 40 for tislelizumab, 14 of 39 for tislelizumab plus surzebiclimab, 11 of 40 for tislelizumab plus alcestobart, and 16 of 40 for the three-agent combination. The other-adverse-event figures are 36 of 40, 32 of 39, 37 of 40, and 39 of 40, respectively. Death counts are also listed by group.

These are descriptive counts, not adjusted comparisons. The groups do not all have the same reported number at risk for the serious and other adverse-event figures, and the registry record does not provide a comparative safety analysis or confidence intervals for these counts. The most frequently listed serious adverse event terms include pneumonia, mouth haemorrhage, pleural effusion, pneumonia aspiration, alanine aminotransferase increased, and aspartate aminotransferase increased, with percentages reported in the registry.

The figures should not be read as establishing a causal difference between groups. The registry record does not provide enough detail to assess event timing, exposure-adjusted rates, severity distribution, or attribution. Safety counts describe what was recorded in this study and should be interpreted separately from the ORR comparisons.

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

The primary result describes the proportion of participants in each treatment group who had a confirmed complete or partial response under investigator assessment using RECIST v1.1 during the stated timeframe. The posted point estimates were 27.5% for tislelizumab alone, tislelizumab plus surzebiclimab, and the three-agent combination, and 25.0% for tislelizumab plus alcestobart. The estimates are accompanied by 95% confidence intervals, which are broad in relation to the group sizes.

The recalculated risk differences are close to zero, and their confidence intervals include zero. This means the posted results do not precisely establish a difference between the combination groups and tislelizumab alone. It does not mean that the groups have been shown to be equivalent, nor does it rule out differences in either direction. Demonstrating equivalence or noninferiority would require a suitable design and prespecified margins, which are not reported in the registry record.

The endpoint is response frequency, not duration of response, progression-free survival, overall survival, or quality of life. Although several of these outcomes are listed as secondary outcomes, numerical results for the remaining listed secondary endpoints are not reported in the registry record. The ORR findings alone cannot answer those separate questions.

The study is randomized, but it is phase 2 and open-label. The posted results therefore provide information about the observed groups, while interpretation remains constrained by the limited precision, the absence of a reported detailed statistical plan, and unreported details about missing data and multiplicity. The record does not establish a clinically important difference threshold. No treatment recommendation follows from these statistics alone.

16. Why This Trial Matters Statistically

This trial raises a useful statistical question: how much can response proportions from relatively small parallel groups tell us about differences between treatment regimens? The registry reports an equal group size of 40 for the primary endpoint, and the ORR estimates are similar across the four groups. Yet the confidence intervals are broad, illustrating why similar point estimates do not settle whether meaningful differences may exist.

The comparison also shows why the estimate, its uncertainty, and the analysis method should be considered together. The recalculated risk differences are unadjusted comparisons derived from the posted summaries, while the registry also reports sponsor analyses. Keeping these summaries distinct prevents a recalculation from being mistaken for the trial's full prespecified analysis. The registry record does not report enough detail to reconstruct that analysis plan.

There are several treatment groups and multiple listed outcomes. That makes the handling of multiplicity important: a collection of unadjusted comparisons should not be interpreted as though it were a single isolated test. The record does not report a multiplicity strategy, so the available results are best understood as descriptive evidence rather than as a complete confirmatory testing framework.

Finally, response is one aspect of clinical outcome. The registry lists other endpoints addressing disease control, time-to-event outcomes, and safety, but those measures have different meanings and require their own interpretation. This study is statistically informative as an example of the distinction between a point estimate and precision, and between absence of clear evidence of a difference and evidence that two regimens are equivalent.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary comparisons are based on groups of 40 participants, and their confidence intervals are broad. As a result, the point estimates alone may give an overly definite impression of similarity or difference. The intervals allow for a range of plausible values, including differences in either direction.

The trial is open-label, and the primary endpoint is investigator-assessed. The registry record does not report whether response assessments were also reviewed independently or whether any sensitivity analysis addressed assessment practices. The endpoint is defined using RECIST v1.1, but the record does not provide further details about assessment schedules or the handling of unevaluable assessments.

The record does not report the detailed statistical analysis plan, a sample-size justification, a multiplicity adjustment, or whether interim analyses were conducted. The posted planning illustrations are based on observed effects and specified assumptions; they are not evidence about the trial's original design. Missing-data methods, sensitivity analyses, and detailed analysis populations for secondary endpoints are also not reported in the registry record.

The registry lists four treatment groups and several secondary outcomes, but numerical results for the remaining listed secondary outcomes are not reported in the registry record. The available ORR results therefore cannot establish conclusions about response duration, progression-free survival, or overall survival. Safety counts are descriptive, and the registry record does not give enough information to compare exposure-adjusted risks or assess event timing and attribution.

These limitations are specific to the information reported for this study. They do not establish that unreported procedures were not conducted; they mean those procedures cannot be evaluated from the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study of Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma — NCT05909904.
• Registry record last updated 2026-09-01; status last verified 2026-08.
• Results first posted 2026-07-14.
• 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.

21. Record Summary

NCT05909904 is a completed, randomized, phase 2, open-label, parallel-group study of tislelizumab alone and in combination with surzebiclimab, alcestobart, or both agents in first-line recurrent or metastatic head and neck squamous cell carcinoma. The registry lists an enrollment of 160.

The primary endpoint was investigator-assessed ORR under RECIST v1.1, with a timeframe of up to 21.2 months and an Intent-to-Treat population defined as all randomized participants. Posted ORR estimates were 27.5% in three groups and 25.0% in the tislelizumab plus alcestobart group. The recalculated unadjusted comparisons have confidence intervals that include zero.

The registry also lists clinical benefit rate, disease control rate, progression-free survival, duration of response, treatment-emergent adverse events, and overall survival. The record does not report a detailed statistical plan, multiplicity strategy, or missing-data methods. The observed results are descriptive and do not establish equivalence between treatment groups.