Lenvatinib and Pembrolizumab Simultaneous Combination Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lenvatinib and Pembrolizumab Simultaneous Combination Study (NCT03609359), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

This question describes tumor response in the study group, not a contrast between treatment strategies. The record does not give a primary response count, response rate, confidence interval, or test result. Consequently, the clinical question can be identified, but its answer cannot be quantified from the registry record.

3. Trial Design

This was an open-label phase 2 study sponsored by National Cancer Center Hospital East. The study evaluated lenvatinib given simultaneously with pembrolizumab in patients with advanced gastric cancer. Its design is recorded as single-group, and allocation is listed as NA. Masking is listed as none, so the record does not describe blinded treatment assignment or blinded outcome assessment.

Enrollment is recorded as 29. The study status is completed. The listed study start date is 2018-10-03, and the primary completion date is 2021-04-30. These dates describe the registry record; they do not, by themselves, provide information about the length of each participant’s treatment or follow-up.

A single-group design can describe outcomes observed among participants receiving the combination, but it does not establish what would have happened to comparable participants under another treatment. Without a concurrent control group, differences from other studies or historical experience cannot be interpreted as randomized treatment effects. The record itself flags that the arms are not a like-for-like control comparison; in this study there is one treatment group.

The registry lists objective response rate as the primary outcome, with a 12-month timeframe. The outcome definition requires complete or partial response as best overall response, with confirmation, according to irRECIST and RECIST v1.1. Listed secondary outcomes include adverse events, immune-related objective response rate, progression-free survival, overall survival, and disease control rate. The registry record does not report detailed procedures for treatment assignment, assessment schedules, follow-up, or analysis populations.

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: ORR will be defined as the proportion of patients who achieved CR or PR for best overall response (confirmation required) according to immune-related RECIST (irRECIST) and RECIST v1.1.

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: Lauren classification (Intestinal type / diffuse type), MMR (Proficient, Deficient), Peritoneal metastasis (Present/ Absent), Programmed Death-Ligand 1 (Positive, Negative), Epstein Barr Virus (Positive, Negative).

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over 12 months.

The primary endpoint is objective response rate (ORR), expressed as the proportion of participants whose best overall response is a confirmed complete response (CR) or partial response (PR). The registry specifies assessment according to immune-related RECIST (irRECIST) and RECIST v1.1, with a 12-month timeframe. Requiring confirmation means an initial response alone is not sufficient under the stated definition.

In general, an objective response endpoint condenses tumor assessments into a binary outcome: a participant either meets the response definition or does not. Reporting both the number meeting the definition and the denominator used allows readers to understand the observed response frequency. A confidence interval, when reported, describes statistical uncertainty around the estimated proportion; it does not remove limitations in study design or establish a treatment effect relative to a comparator.

ORR is used to describe whether tumor shrinkage meeting the specified criteria was observed. It does not, on its own, summarize how long a response lasts, how long participants live without progression, overall survival, or the balance of benefits and harms. Those are separate outcomes. Although the registry lists ORR as primary, it does not report the number with a confirmed response, the denominator analyzed, an estimated rate, or an uncertainty interval. The endpoint is defined, but its numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a binary primary outcome: participants are counted according to whether they achieve a confirmed CR or PR. In general, a binary endpoint can be summarized by a count of participants meeting the definition and a denominator for the relevant analysis population. The resulting proportion is a descriptive estimate of how frequently the defined outcome occurred in that population. The registry record does not report the response count, analysis denominator, or estimated proportion for this study.

What does a confidence interval add?

In general, a confidence interval expresses sampling uncertainty around an estimate. For a response proportion, it helps distinguish a relatively precise estimate from one that is compatible with a wider range of underlying response frequencies. Its width depends on the amount of information and the pattern of observed outcomes, among other factors. A confidence interval is not a guarantee that the true value lies within its limits, and it does not account for every source of bias. No confidence interval for the primary endpoint is reported in the registry record.

Why does the single-group design matter?

A single-group study can describe outcomes during treatment, but does not observe a concurrent group receiving a different treatment or control condition. General statistical comparisons require a contrast: an outcome under one condition compared with an outcome under another. When there is no randomized comparator, an observed response frequency cannot isolate the effect of the treatment combination from participant selection, disease course, assessment practices, or other influences. This is a design limitation, not something a statistical test can remedy after the fact.

The record lists allocation as NA and masking as none. It does not describe random assignment or blinding. It also does not report details of independent review or outcome-assessment procedures. Those details matter because response classification depends on assessment and on applying the response criteria consistently. The registry identifies irRECIST and RECIST v1.1 and states that confirmation is required, but does not report how assessments under the two criteria were reconciled or which result was used for each participant.

What can a count-based result tell readers?

In general, a count communicates how many participants met an event definition, while the denominator gives the context needed to interpret that count. Counts alone do not reveal the uncertainty of a rate or support a comparison between treatment groups. For this study, the record gives enrollment but does not identify the primary endpoint analysis denominator or provide the response count. It is therefore not appropriate to infer a rate from enrollment or to treat every enrolled participant as assessed.

For safety outcomes, the registry lists affected-participant counts and counts at risk. A count of participants with an event is different from a count of event episodes: one participant may experience more than one event, but the record does not specify event-level totals or the counting rules in detail. Serious adverse events are also distinct from other adverse events as registry categories. Neither category alone establishes that treatment caused an event.

How should planning calculations be read?

General sample-size planning asks how much information a future study might need to detect a chosen effect under stated assumptions. The record’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. For time-to-event outcomes, the planning quantities are total events; for other outcomes, they are participants per arm.

These assumptions describe planning illustrations, not the design of the registered study. The registered study is single-group, not an equal-allocation two-arm trial. A planning calculation based on an observed effect is conditional on that effect and on the assumptions; it does not establish that the study had a given probability of detecting a treatment effect. Such a probability would be called power, and a planning illustration must not be recast as observed power. The trial’s own sample-size justification and statistical plan are not reported in the registry record.

What analysis details are absent?

The record reports zero analyses. It does not report a model for the primary outcome, an inferential test, adjustment variables, a confidence interval method, or analysis-population definitions. These details should not be inferred from the endpoint definition or from the fact that response is binary. Nor does the record state how missing assessments, withdrawals, or unevaluable responses were handled. Without those details and the primary result, readers cannot assess the statistical precision or robustness of the endpoint estimate.

Finally, the record lists multiple secondary outcomes. In general, when many outcomes or statistical tests are examined, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. The registry record does not report whether or how multiplicity was handled. This absence does not prove that no such plan existed; it means the plan is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome, ORR, and several secondary outcomes: number of participants with adverse events, immune-related ORR, progression-free survival, overall survival, and disease control rate. It does not report a multiplicity strategy, such as a prespecified ordering of tests or an adjustment for examining multiple outcomes. In general, multiplicity matters when several statistical hypotheses are tested because the chance of at least one chance-positive finding can rise as the number of tests increases. The record does not provide enough detail to determine whether this issue was addressed in the study’s analysis plan.

Missing-data methods are also not reported in the registry record. The primary endpoint requires a confirmed response, but the record does not explain how participants with missing, incomplete, or unevaluable assessments were classified or whether they were excluded from an analysis. Enrollment of 29 does not establish the denominator used for ORR. The response count, denominator, and analysis population are not reported.

The record does not define analysis populations for the primary or secondary outcomes, such as which participants were included in each analysis. It also does not report a statistical analysis plan, the handling of protocol deviations, or sensitivity analyses. These omissions limit assessment of how the endpoint definition was translated into an analyzed result. They do not establish that such procedures were absent from the conduct of the study; they are not reported in the registry record.

11. 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: jaundice cholestatic (3.4%), caridiac failure (3.4%), gastirc haemorrhage (3.4%), gastric perforation (3.4%).

The registry record lists 29 participants at risk for serious adverse events and 4 affected by serious adverse events. For other adverse events, it lists 29 at risk and 29 affected. It also records 15 deaths. These are counts in the registry record, not comparative estimates against a control group. The record does not state whether the deaths were considered treatment-related, so the count should not be interpreted as evidence of causation.

Four serious-event terms are listed, each with a registry percentage of 3.4%: Jaundice cholestatic, Caridiac failure, Gastirc haemorrhage, and Gastric perforation. The spellings are reproduced as recorded. The record does not give further context about timing, duration, clinical course, or attribution for these terms. The listed terms and percentages should therefore be read as registry safety entries rather than as a complete account of each participant’s experience.

In general, adverse-event counts are descriptive and depend on how events were collected, classified, and attributed. The registry record does not provide enough information to assess those procedures or to compare safety with another treatment. The single-group design offers no concurrent control for such a comparison.

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

The registry record defines a clinically interpretable primary outcome: confirmed complete or partial response within the stated 12-month timeframe, assessed using irRECIST and RECIST v1.1. It also identifies a treatment combination, a population with advanced gastric cancer, and a single-group phase 2 design. These details clarify what the study was intended to evaluate.

However, the record does not report the primary response count, analysis denominator, response rate, confidence interval, or a statistical test. It therefore does not show how frequently confirmed responses occurred in the analyzed population or how precise an estimate might be. The numerical primary result cannot be inferred from enrollment alone.

Even if a response estimate were available, a single-group result would describe the observed study group rather than establish a comparative effect. Without a concurrent control group, the study cannot by itself separate treatment effects from other explanations for observed outcomes. An observed response would not, on its own, establish effects on survival, duration of response, quality of life, or other outcomes not captured by ORR.

The registry lists secondary outcomes and safety counts, but the presence of an outcome in the record is not the same as a reported analysis. Safety counts do not establish causation, and the death count has no reported attribution in the record. No comparative safety conclusion can be made from this single-group information.

Overall, the record supports a description of the study’s purpose, design, and selected safety entries. It does not report the numerical primary efficacy result or the analysis details needed to evaluate its statistical uncertainty. These limits concern what can be concluded from the registry record, not necessarily every analysis or detail that may exist outside it.

13. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and a reported endpoint result are different things. The registry clearly defines ORR as confirmed CR or PR and identifies the response criteria and timeframe. Yet it does not report the response count, denominator, or rate. A clearly specified outcome is important for interpreting a trial, but readers also need the observed result and an account of its uncertainty.

The single-group design makes the distinction between description and comparison especially important. A response frequency in participants receiving lenvatinib with pembrolizumab would describe that group. It would not provide a randomized estimate of how outcomes differed from an alternative. This matters when readers encounter a response outcome without a control group: the statistic has a descriptive meaning, but a causal interpretation requires more than an observed proportion.

The record also makes a useful distinction between primary and secondary outcomes. ORR is designated primary, while adverse events, immune-related ORR, progression-free survival, overall survival, and disease control rate are listed as secondary. Without a reported statistical plan, analysis populations, or multiplicity approach, it is not possible to assess how the outcomes were analyzed or whether inferential claims were prioritized in advance.

Finally, the safety entries show why counts need context. The record separately lists serious and other adverse events and records deaths, but does not provide comparative data or attribution details. Statistical interpretation must preserve that distinction: an event recorded during a study is not automatically an event caused by the study treatment. Together, these features make the registry record useful for identifying the question and the limits of the available evidence, while leaving the primary numerical result unresolved.

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 most direct limitation is that the registry record does not report the primary endpoint result. It provides no confirmed-response count, analysis denominator, ORR estimate, confidence interval, or test result. Enrollment is listed as 29, but the record does not establish that all enrolled participants contributed to the primary analysis.

The study is single-group, with no randomized comparator. Consequently, the design cannot support a like-for-like treatment contrast, and outcomes in the treatment group cannot by themselves establish what would have occurred under another condition. Open-label conduct and the absence of masking are recorded; the record does not describe procedures that might limit assessment bias.

Several operational and statistical details are not reported in the registry record, including eligibility criteria beyond the stated condition, treatment dosing, assessment schedules, analysis populations, missing-data handling, a statistical analysis plan, and multiplicity procedures. The record identifies both irRECIST and RECIST v1.1 but does not explain how their assessments were used in analysis.

Safety information is also limited to registry entries. The record lists affected-participant counts, selected serious-event terms, and deaths, but does not give detailed event timing, attribution, or a concurrent comparison. The listed data therefore do not establish that events were caused by treatment or allow comparative safety assessment. These limitations describe what is not reported in the registry record and should not be taken as proof that the information does not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Lenvatinib and Pembrolizumab Simultaneous Combination Study — NCT03609359.
• Registry record last updated 2025-04-16; status last verified 2025-03.
• Results first posted 2025-04-16.
• 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.

18. Record Summary

NCT03609359 is a completed, open-label phase 2, single-group study sponsored by National Cancer Center Hospital East. It evaluated simultaneous lenvatinib and pembrolizumab in advanced gastric cancer. Enrollment is recorded as 29; the study start date is 2018-10-03 and the primary completion date is 2021-04-30.

The primary outcome is ORR, defined by confirmed CR or PR as best overall response according to irRECIST and RECIST v1.1, with a 12-month timeframe. The record lists secondary outcomes covering adverse events, immune-related ORR, progression-free survival, overall survival, and disease control rate. It records safety counts but does not report the primary response result or statistical analyses. The single-group design does not provide a randomized control comparison.