IO102-IO103 in Combination With Pembrolizumab as First-line Treatment for Patients With Metastatic NSCLC, SCCHN, or mUBC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IO102-IO103 in Combination With Pembrolizumab as First-line Treatment for Patients With Metastatic NSCLC, SCCHN, or mUBC (NCT05077709), a non-randomized phase 2 study. The primary outcome is ORR.

2. Clinical Question

In general, objective response rate describes the share of an eligible population whose tumors meet prespecified response criteria. Confirmation is intended to distinguish a response supported by subsequent assessment from a response seen only once. The registry identifies the measurement criteria and the population, but does not provide the assessment schedule, response counts, or uncertainty interval for the primary endpoint.

3. Trial Design

This was a phase II, multi-arm basket trial of IO102-IO103 combined with pembrolizumab as first-line treatment for patients with metastatic NSCLC, SCCHN, or mUBC. The registry reports a parallel model, non-randomized allocation, and no masking. Its enrollment entry is 63, and its status is completed. The record gives a start date of 2022-04-11 and a primary completion date of 2025-11-30.

The arms correspond to the three disease groups: Arm A is NSCLC, Arm B is SCCHN, and Arm C is mUBC. Each arm description specifies IO102-IO103 subcutaneously Q3W with pembrolizumab intravenously at 200mg Q3W. These are separate disease cohorts receiving the combination, rather than randomized groups assigned to competing regimens.

The non-randomized design matters for interpretation. Arm membership is tied to disease group, so differences in outcomes across arms could reflect differences in the diseases or patient characteristics as well as any variation in treatment experience. There is no concurrent randomized comparator described in the registry record. Consequently, the study design does not support a direct causal comparison between the arms or against another treatment.

The listed primary outcome is confirmed ORR according to RECIST v1.1, with assessment extending from informed consent until disease progression, death, or withdrawal of consent, whichever came first, for up to 3 years. The endpoint population requires at least two cycles of treatment and an evaluable post-baseline tumor assessment. The record also lists PFS, DoR, CRR, DCR, OS, and TTR as secondary outcomes. It does not report arm-specific enrollment, follow-up completeness, or the primary endpoint analysis.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All patients who received at least two cycles of study treatment and had at least one evaluable post baseline tumor assessment.

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 ORR, measured over From date of informed consent until disease progression, death or withdrawal of consent whichever came first, assessed for up to 3 years..

The primary endpoint is confirmed objective response rate according to RECIST v1.1. The registry defines the endpoint population as patients who received at least two cycles of study treatment and had at least one evaluable post-baseline tumor assessment. The stated observation period begins at informed consent and continues until disease progression, death, or withdrawal of consent, whichever came first, for up to 3 years.

In general, ORR is a binary outcome at the participant level: each person is classified according to whether the prespecified response criteria are met. A response endpoint can provide a direct measure of tumor shrinkage under defined assessment rules. Confirmation aims to make the classification less dependent on a single assessment. The registry record does not specify the detailed confirmation schedule or report response counts, an estimated rate, or a confidence interval.

The endpoint population definition affects what the result would represent. It excludes people who did not receive the required treatment exposure or lack an evaluable post-baseline assessment. Thus, even if an ORR estimate were reported, it would apply to that defined population, not automatically to every person enrolled or considered for treatment. The number included in the primary analysis is not reported in the registry record.

ORR is not interchangeable with the listed secondary outcomes. In general, PFS and OS concern time until events, while DoR and TTR describe timing among response-related outcomes; CRR and DCR use different response classifications. The registry lists these outcomes but does not provide their results in the record described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: confirmed objective response, recorded as a count of participants. In general, a binary endpoint classifies each participant into an outcome category, such as response or no response. To estimate a response rate, the analysis needs both the number meeting the response definition and the number included in the endpoint population. Neither the primary response count nor the analyzed denominator is reported in the registry record, so no rate can be interpreted from it.

What does confirmation contribute?

In general, confirmation requires a response classification to be supported by assessment beyond the initial observation, according to the study’s response rules. This can reduce the chance that a transient or uncertain finding is treated as a confirmed response. The registry identifies RECIST v1.1 and calls the outcome confirmed ORR, but does not report the detailed assessment schedule, confirmation rule, or response data.

Why does the analysis population matter?

The stated primary population includes patients who received at least two cycles and had at least one evaluable post-baseline tumor assessment. This definition is important because an endpoint estimate applies to the people who qualify for that analysis, not necessarily to everyone enrolled. Excluding participants without sufficient treatment or an evaluable assessment can affect how representative the estimate is. The registry does not report the number meeting the criteria, the number excluded, or the reasons for exclusion.

In general, analysis-population rules should be defined before outcome results are examined, and the report should make clear how participants with incomplete assessments are handled. Different rules can lead to different denominators or response classifications. The statistical plan and missing-data approach for this trial are not reported in the registry record.

How should uncertainty be assessed?

A response estimate is more informative when accompanied by a confidence interval. In general, the interval describes statistical uncertainty around the estimate under specified assumptions; it is not a guarantee that the true value lies within a particular range. The interval’s width depends in part on the amount of information in the analysis. Since the record does not report an ORR estimate, denominator, or interval, precision cannot be assessed.

A significance test, when prespecified and appropriate, addresses compatibility between data and a stated statistical hypothesis. It does not by itself measure clinical importance, eliminate bias, or establish causality. The registry record does not report an ORR test, p-value, or prespecified hypothesis. It also does not report whether analyses were adjusted for other variables.

What does the design imply for comparisons?

The trial uses non-randomized, parallel arms assigned by disease group. Random assignment is generally used to balance known and unknown participant characteristics across treatment groups, in expectation. Without randomization, comparisons between arms may be confounded by differences between the disease populations or other characteristics. Here, the arms are not a control comparison, and their contrast cannot isolate a treatment effect.

Masking is listed as none. In general, masking can reduce the influence of knowledge about treatment assignment on assessments or other study procedures. Its absence may matter especially when outcome assessment involves judgment, although the registry does not describe assessment procedures or whether outcome assessors were independent. The record does not allow the extent or direction of any potential bias to be quantified.

How do the planning assumptions differ from observed power?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those are assumptions for a planning exercise, not evidence about the trial’s achieved power. The illustration is not the trial’s own design justification, and equal allocation between two arms does not describe the three disease-specific arms in the registry. Planning sample sizes are not outcomes and do not replace an analysis of observed data.

In general, power is a prospective property based on assumptions about an effect, variability, design, and analysis. Calculating power after results are observed does not establish that a finding is reliable or that a non-significant result demonstrates no effect. The trial’s sample-size justification, target effect, and any formal power calculation are not reported in the registry record.

What about secondary outcomes and multiple testing?

The registry lists PFS, DoR, CRR, DCR, OS, and TTR as secondary outcomes. In general, testing or estimating multiple outcomes raises questions about how results are prioritized and whether a multiplicity strategy is used. Such a strategy can affect the interpretation of statistical significance across outcomes. The registry record does not report a multiplicity procedure, analysis results, or a statistical analysis plan. The outcomes’ definitions, analysis populations, and handling of competing events or censoring are also not reported.

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("Arm A (NSCLC)", "Arm B (SCCHN)", "Arm C (mUBC)")
n      <- c(31, 18, 3)
events <- c(15, 8, 2)
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  Arm A (NSCLC)  31  15  48.4  30.2  66.9  32.0  65.2  31.9  65.3
ARM  Arm B (SCCHN)  18  8  44.4  21.5  69.2  24.6  66.3  24.4  66.5
ARM  Arm C (mUBC)  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists PFS, DoR, CRR, DCR, OS, and TTR as secondary outcomes alongside confirmed ORR as the primary endpoint. Considering several outcomes can raise multiplicity concerns: in general, repeated statistical testing can increase the chance of at least one apparently notable result when all tests are interpreted together. A prespecified strategy may prioritize outcomes, adjust significance thresholds, or treat secondary analyses as exploratory. The multiplicity approach is not reported in the registry record.

The record does not report the statistical analysis plan, endpoint-specific analysis methods, or any analysis entries. It therefore does not establish which outcomes were formally tested, how results were prioritized, or whether any adjustment was used. No primary or secondary outcome estimates are reported in the record described, so consistency among endpoints cannot be evaluated.

Missing outcome data are particularly relevant to the primary endpoint because inclusion requires at least two treatment cycles and an evaluable post-baseline tumor assessment. The record does not give the number of participants who met those criteria, the number with missing or unevaluable assessments, or the reasons for missingness. It also does not report whether missing assessments were treated as non-response, excluded, imputed, or handled through another method. These choices can alter the analyzed population and the resulting estimate.

In general, missingness can be informative when the chance of an unavailable assessment is related to a participant’s health or outcome. A clear report would describe the extent and reasons for missing data and explain the analysis assumptions. Those details are not reported in the registry record. Thus, the potential influence of incomplete assessment on the primary endpoint cannot be evaluated.

The time-to-event secondary outcomes would also require clear definitions of event, censoring, and analysis population. These methods are not reported. No conclusion about their handling or the robustness of their results can be drawn from the registry information.

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: atrial fibrillation (20.0%), eye discharge (20.0%), escherichia bacteraemia (20.0%), spinal fracture (20.0%), ischaemic stroke (20.0%).

The registry reports serious adverse event counts by arm. In Arm A (NSCLC), 5 participants were affected among 37 at risk; in Arm B (SCCHN), 2 were affected among 21 at risk; and in Arm C (mUBC), 1 was affected among 5 at risk. The record also lists other adverse event counts: 33 among 37 at risk in Arm A, 21 among 21 at risk in Arm B, and 5 among 5 at risk in Arm C. Deaths are listed as 4, 1, and 1 in Arms A, B, and C, respectively.

These are counts, not comparative estimates of treatment risk. The arms contain different disease groups and are not randomized control groups. The counts alone do not establish that treatment caused an event or death. The registry record does not state the relationship of these events to study treatment or provide a comparative safety analysis.

The record lists atrial fibrillation, eye discharge, Escherichia bacteraemia, spinal fracture, ischaemic stroke, and pneumonitis among the top serious terms, each at 20.0%. These term percentages should be interpreted as registry-reported values; the record does not give enough detail to infer their precise denominators or make between-arm comparisons. In general, safety counts need context about event definitions, exposure, follow-up, severity, and attribution. Those details are not reported in the registry record.

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

The registry record establishes that a phase II, non-randomized basket trial evaluated IO102-IO103 with pembrolizumab as first-line treatment across metastatic NSCLC, SCCHN, and mUBC arms. It identifies confirmed ORR according to RECIST v1.1 as the primary endpoint and describes the endpoint population. It also lists secondary outcomes and reports adverse event counts.

The record does not report the primary response count, ORR estimate, confidence interval, or statistical test. It therefore does not show how often confirmed responses occurred or how precisely an ORR was estimated. The completed status does not supply those missing outcome results. The record also does not report the analyses for PFS, DoR, CRR, DCR, OS, or TTR.

The design cannot establish a treatment effect relative to a control because there is no randomized comparator. The arms are organized by disease group, so any difference between them would not be a like-for-like treatment contrast. Even if outcomes were available, unadjusted comparisons across these arms would not identify whether observed differences arose from the treatment or from differences between the populations.

The adverse event figures describe recorded counts in the listed groups. They do not, by themselves, show causation or comparative risk. The registry does not report treatment attribution or a safety analysis that would support those conclusions.

In general, trial interpretation depends on more than whether a study is complete or whether a result is statistically significant. The endpoint definition, analysis population, uncertainty, missing-data approach, and study design all shape what can be inferred. For this record, the absence of reported efficacy analyses and the non-randomized design limit interpretation. The information supports a description of what was studied, but not a claim that the regimen does or does not work.

14. Why This Trial Matters Statistically

This trial illustrates why the structure of a study matters as much as its endpoint. A basket design can examine a treatment combination across distinct disease groups, while keeping each group identifiable. Here, the disease-specific arms make clear which population each treatment description concerns. At the same time, non-randomized assignment means the arms are not interchangeable comparison groups.

The primary endpoint is defined with both a response criterion and an analysis-population rule. That specificity is statistically important: an estimate depends on how response is classified and who is included in its denominator. The requirement for at least two cycles and an evaluable post-baseline assessment makes the endpoint population different in principle from the enrollment entry. The number analyzed is not reported, so this distinction cannot be resolved from the registry record.

The record also highlights the difference between a completed trial and a reported analysis. A completed status gives information about trial status, but does not itself provide an effect estimate, its precision, or evidence about secondary outcomes. Without those results, readers cannot evaluate response magnitude, uncertainty, or consistency across endpoints.

Finally, the trial’s safety counts show why descriptive event reporting should not be mistaken for causal comparison. The disease-specific arms have different populations, and there is no randomized control arm. Counts can describe what was recorded, but interpretation also depends on exposure, follow-up, definitions, and treatment attribution. Those considerations are not fully reported in the registry record.

These statistical distinctions are useful when reading early-phase clinical research: endpoint definitions, analysis populations, uncertainty, and design determine what conclusions the data can support. In this case, the registry record describes the study but does not report enough efficacy analysis to quantify the primary outcome.

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 central limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. There is no response count, ORR estimate, confidence interval, or reported test. The status is completed, but the outcome information needed to judge the result’s magnitude and precision is not reported in the registry record.

The primary analysis population is defined by treatment exposure and evaluable post-baseline assessment, while the number meeting that definition is not reported. Arm-specific enrollment, exclusions, missing assessments, and reasons for missingness are also not reported. This prevents assessment of how the analyzed population relates to enrollment or whether missing data could affect the endpoint.

The trial is non-randomized and has no masking. The three arms correspond to different diseases and are not control comparisons. Consequently, arm-to-arm differences would be difficult to interpret as treatment differences. The record does not provide adjusted analyses that might address measured population differences, and it does not describe the outcome assessment procedures in enough detail to evaluate potential assessment bias.

The statistical analysis plan, sample-size justification, multiplicity strategy, and analysis methods for the secondary outcomes are not reported in the registry record. The planning assumptions described for an illustration are not the trial’s own design justification and do not establish observed power. Outcome definitions and missing-data methods for the secondary endpoints are also not reported.

Safety interpretation is limited by the absence of reported treatment attribution and comparative analyses. The serious event and death counts are descriptive. The term-level percentages are listed, but the record does not provide sufficient context to infer their denominators or compare risks across arms. These limitations restrict conclusions to the design and counts explicitly recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: IO102-IO103 in Combination With Pembrolizumab as First-line Treatment for Patients With Metastatic NSCLC, SCCHN, or mUBC — NCT05077709.
• Registry record last updated 2026-04-08; status last verified 2026-03.
• Results first posted 2026-04-08.
• 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

NCT05077709 is a completed phase II, non-randomized, parallel basket trial sponsored by IO Biotech. It evaluated IO102-IO103 with pembrolizumab as first-line treatment for metastatic NSCLC, SCCHN, or mUBC. The enrollment entry is 63. The record lists the trial start as 2022-04-11 and primary completion as 2025-11-30.

The primary outcome is confirmed ORR according to RECIST v1.1 among patients who received at least two cycles and had an evaluable post-baseline tumor assessment. The record lists PFS, DoR, CRR, DCR, OS, and TTR as secondary outcomes. Primary and secondary efficacy analyses are not reported in the registry record.

The registry reports serious and other adverse event counts by arm, as well as deaths and selected serious event terms. These figures are descriptive and do not establish treatment causation or a comparative effect. The non-randomized, disease-specific arms are not a like-for-like control comparison.