Abemaciclib Plus Ramucirumab for Esophageal/Gastroesophageal Junction Ca: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Abemaciclib Plus Ramucirumab for Esophageal/Gastroesophageal Junction Ca (NCT04921904), a na phase 1, phase 2 study. The primary outcome is Safety of Abemaciclib + Ramucirumab.

2. Clinical Question

The clinical question is about safety in a metastatic cancer population, rather than a randomized comparison of the combination with another treatment. The registry also lists objective response rate, progression free survival, overall survival, and rate of stable disease as secondary outcomes. Their outcome names indicate areas of interest, but they do not establish that results for those outcomes are present. Those results are not reported in the registry record.

The record’s rationale notes that CDK4/6 and Cyclin D1 are expressed in approximately 80% of esophageal and gastroesophageal junction tumors, and proposes CDK4/6 inhibition as a potential strategy in diseases described as resistant to chemotherapy and immunotherapy. This is the rationale recorded for studying the combination; it is not itself evidence of benefit or safety. The study’s posted safety counts provide a descriptive account of events, not a treatment-effect estimate against a control group.

3. Trial Design

This is a Phase I/II study with a single-group model. The record lists an enrollment of 26 and describes participants as receiving abemaciclib plus ramucirumab. Allocation is recorded as not applicable, and masking is listed as none. There is no randomized comparison, so the results cannot directly contrast this regimen with a control arm under the same trial conditions.

The listed regimen is abemaciclib 150mg orally twice daily every day together with ramucirumab 8mg/kg intravenously every 2 weeks. Treatment is described as continuing until evidence of disease. The registry identifies Baylor Research Institute as the sponsor. The study began on 2021-06-11, had a primary completion date of 2024-12-31, and is recorded as completed.

The primary outcome is safety, expressed as a count of participants. Its stated observation period begins at enrollment and continues through treatment and follow-up, ending 100-days after the last dose or at death from any cause, whichever occurred first; the record says this was assessed up to 24 months. The stated endpoint population includes participants who received at least one dose. The posted adverse-event group lists 26 participants at risk for serious events and 26 at risk for other adverse events.

Phase I/II describes the study’s registry classification, but the registry record does not report the protocol details needed to explain how the phases were operationally divided. It also does not report a sample-size justification, interim-analysis plan, or detailed statistical analysis plan. Because the design is single-group, its safety counts are descriptive and do not provide a controlled estimate of the regimen’s effect relative to another treatment.

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

Analysis population for the primary outcome, as defined in the registry: Includes all participants who received at least one dose of treatment.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Safety of Abemaciclib + Ramucirumab, measured over From date of study enrollment, through treatment, and during follow-up until 100-days after the last dose of study medication or death, from any cause, whichever occurred first, assessed up to 24 months.

The primary endpoint is titled safety and is measured as a count of participants. Its description focuses on participants experiencing adverse events and serious adverse events of Grade 3 or higher while on study, assessed using CTCAE v4.0 criteria. The endpoint’s stated population includes all participants who received at least one dose of treatment. The observation period begins at enrollment and extends through treatment and follow-up until 100-days after the last dose or death from any cause, whichever occurred first, with assessment up to 24 months recorded.

A participant count is useful for describing how many people in the treated group experienced an event meeting the endpoint definition. It is directly interpretable as a tally within the study population, but by itself does not describe event timing, duration, recurrence, or the total number of episodes. A count also does not establish that treatment caused an event. In a single-group study, there is no randomized control group to distinguish events associated with treatment from events that might occur because of the underlying illness or other circumstances.

The posted adverse-event results give counts for serious adverse events and other adverse events, but the registry record does not provide a separate grade breakdown with those counts. It also does not report a confidence interval or a statistical comparison for the primary endpoint. The event counts should therefore be read as descriptive safety observations, with the endpoint definition and limitations kept in view.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event summarized as a count: each participant either experienced an event meeting a stated category or did not. This makes the reported result a descriptive tally. The count is not the same as the number of event episodes, since a participant may experience more than one event. The record does not say whether individuals could be represented in both the serious and other adverse-event categories, so those counts cannot be treated as mutually exclusive groups.

What does a participant count tell the reader?

A count is straightforward to interpret within the observed study group, but it does not by itself express uncertainty. In general, statistical uncertainty describes how much a result might vary across comparable samples. A confidence interval is one common way to show that uncertainty around an estimate. No confidence interval for the primary safety result is reported in the registry record, so the precision of the posted counts cannot be assessed from an interval there. The same limitation applies to the absence of a reported hypothesis test.

For a binary outcome, a common general model treats each participant’s event status as a Bernoulli observation and the group count as arising from a binomial distribution. That framework relies on assumptions about the observations and outcome definition. It can provide a basis for estimating an event probability and its uncertainty, but the registry record gives the endpoint in counts and does not report the model or interval method used. No event probability or uncertainty measure should be inferred beyond what is explicitly posted.

Why does the study design matter?

A randomized comparison can support a more direct estimate of the difference between treatment groups because random assignment is intended to make the groups comparable on average. This study is recorded as single-group, with allocation not applicable and no masking. It therefore lacks an internal randomized control group. Any comparison with results from other studies would be indirect and could be influenced by differences in eligibility, background care, follow-up, and how outcomes were measured. A single-group count remains informative as a record of observed events, but it does not isolate a treatment effect.

The sample-size assumptions describe a planning illustration, not the study’s original design: the illustration is based on the observed effect and uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. The registry record does not report the output of those illustrations in the registry record for this analysis. More importantly, the assumptions do not turn the single-group study into a two-arm randomized trial. Such planning calculations are not observed power and are not evidence that the study was powered to detect a particular effect.

How should the event terms be interpreted?

Safety reporting may include a participant-level count, event terms, severity grades, seriousness, and judgments about relationship to treatment. These dimensions are not interchangeable. A serious adverse event is classified by regulatory seriousness criteria, while a severity grade describes intensity. The primary endpoint specifies Grade 3 or higher events assessed with CTCAE v4.0, but the posted counts do not show grades or provide participant-level cross-classification of seriousness and severity. The six listed serious-event terms each carry a reported percentage, but the record does not explain whether these terms represent unique participants, event episodes, or all qualifying serious events. They should be read as the registry’s reported term-level entries, not used to reconstruct missing detail.

Over-dispersion is a general concern when observed binary outcomes vary more than a simple binomial model expects, for example because outcomes cluster or participants differ in ways not represented by the model. A model that ignores extra variation can understate uncertainty. The registry record does not report an over-dispersion assessment or a model-based safety analysis, and the posted count data do not establish whether over-dispersion is relevant in this study.

Finally, outcome reporting and analysis reporting are distinct. The record lists five outcome measures and zero analyses. This does not establish that no analyses were performed; it means analysis details are not reported in the registry record. Without analysis specifications, the reader cannot determine how the listed secondary outcomes were analyzed, how missing observations were handled, or whether any adjustments were made for multiple outcomes.

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("Abemaciclib Plus Ramucirumab")
n      <- c(20)
events <- c(10)
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  Abemaciclib Plus Ramucirumab  20  10  50.0  27.2  72.8  29.9  70.1  29.8  70.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists objective response rate, progression free survival, overall survival, and rate of stable disease as secondary outcomes in addition to the primary safety outcome. It does not report the results of those secondary outcomes or identify a statistical plan for testing them. The record lists zero analyses. Thus, it is not possible to tell from the registry record whether formal hypothesis tests were conducted, which outcome comparisons were prespecified, or whether any adjustment for multiple testing was used.

Multiplicity arises when several outcomes or hypotheses are examined: even if each individual test uses a conventional threshold, the chance of at least one chance finding can increase across a collection of tests. In general, a prespecified testing hierarchy or multiplicity adjustment can help control that issue. Neither the use nor non-use of such an approach is reported in the registry record, so no conclusion about multiplicity control is warranted.

Missing-data handling is also not reported in the registry record. It does not state how participants with incomplete follow-up, missing outcome assessments, or treatment discontinuation were handled in the safety or secondary-outcome analyses. The stated primary safety population includes participants who received at least one dose, but this does not specify how missing event information was managed after treatment began.

The registry record does not describe analysis populations beyond the primary endpoint’s stated treated population, nor does it explain whether any alternative populations were used. Consequently, the posted counts should be read with the recorded denominator and endpoint description, without assuming a particular approach to missing data, censoring, or analysis-set membership.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: enteritis (3.8%), hematemesis (3.8%), parainfluenza (3.8%), pneumococcal disease (3.8%), fracture (3.8%).

The adverse-event group records 6 participants with serious adverse events among 26 at risk and 17 participants with other adverse events among 26 at risk. The categories should remain separate: the registry record does not report whether participants could be counted in both. It also lists 11 deaths, without giving enough detail to connect those deaths to the event categories or to determine their causes.

The primary safety description refers to adverse events and serious adverse events of Grade 3 or higher, assessed using CTCAE v4.0. The group counts do not include a grade breakdown, so they should not be assumed to represent only events of Grade 3 or higher. The record does not report event-level timing, duration, recurrence, treatment relatedness, or outcomes.

Six serious-event terms are listed, each with a reported 3.8%: Enteritis, Hematemesis, Parainfluenza, Pneumococcal Disease, Fracture, and Stroke. Those percentages should be understood as the registry’s term-level reporting. The record does not specify whether each term refers to a participant or an event episode, and the terms do not show that the treatment caused the events. These data are descriptive safety observations in a single-group study, not a comparison with an untreated or alternative-treatment group.

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

The results show that adverse events were recorded among participants treated with abemaciclib plus ramucirumab. The registry lists 6 participants with serious adverse events and 17 with other adverse events, each category having 26 at risk. It also lists 11 deaths and six serious-event terms, each reported as 3.8%. These are observations from the study group, not comparative estimates.

The counts do not establish that the combination caused the events, nor do they show what would have happened to comparable participants under another treatment. The single-group design has no randomized control group for that comparison. A causal interpretation would require information and assumptions beyond the posted counts. The event terms also do not provide a complete picture of clinical course, seriousness criteria, severity grade, relationship to treatment, or participant overlap.

The registry’s primary endpoint description focuses on Grade 3-or-higher adverse events and serious adverse events, but the posted counts do not separately identify events meeting that grade threshold. No confidence interval or statistical analysis for the primary outcome is reported. This limits assessment of precision as well as interpretation of the exact endpoint-specific event burden.

The registry lists several secondary outcomes, including response and survival outcomes, but their results are not reported in the registry record. The safety data therefore cannot be used to infer whether tumors responded, how long participants remained free from progression, or overall survival. The results do not demonstrate efficacy, and the absence of reported secondary results is not evidence that no such outcomes were collected.

In short, the record offers a descriptive account of safety reporting during the specified observation period. It does not establish a comparative treatment effect, resolve causality, or answer the listed efficacy questions. These boundaries are essential when interpreting a small single-group clinical study.

14. Why This Trial Matters Statistically

This study is statistically notable because its central question is framed around safety in a single treatment group, while the registry also names clinical outcomes that could ordinarily invite comparative or time-to-event analyses. The design and outcome reporting must be distinguished: listing an outcome does not provide an estimate, and recording events does not create a control comparison.

Participant-level counts are valuable in early-phase research because they describe which safety signals were observed in the treated group. Yet the statistical meaning depends on how events are defined, how follow-up is handled, and whether counts refer to participants or episodes. The registry describes a Grade 3-or-higher safety endpoint but posts event-category counts without a grade-specific breakdown. That gap illustrates why endpoint definitions and result details need to align before a count can be interpreted as the primary endpoint result.

The single-group structure also highlights the role of design in statistical inference. A treatment-group count can characterize experience in that group, but it cannot by itself show whether the count differs from what would occur without the treatment or under another regimen. Such distinctions are important when readers encounter safety data from an uncontrolled study.

The record’s secondary outcomes include response, progression-free survival, overall survival, and stable disease, but corresponding results and analysis details are not reported in the registry record. This makes the record useful for understanding what the study set out to monitor, while limiting what can be concluded about those outcomes. The sample-size planning assumptions are explicitly an illustration based on observed effect, rather than a reconstruction of the trial’s original design. Together, these features underscore that statistical interpretation depends on design, endpoint specificity, and transparent reporting—not counts alone.

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 principal limitation is the single-group design. There is no randomized comparator, so the posted event counts cannot estimate a relative safety effect or distinguish treatment-associated events from events attributable to the underlying disease or other factors. The study is not a like-for-like control comparison.

The posted safety information is limited in detail. Although the primary endpoint specifies Grade 3-or-higher adverse events and serious adverse events assessed using CTCAE v4.0, the adverse-event counts are not broken down by grade. The record does not report event timing, duration, recurrence, relatedness, outcome, or whether serious-event terms represent unique participants or event episodes. It also does not state whether participants could contribute to both the serious and other adverse-event categories.

The record lists 11 deaths but does not provide a cause breakdown or explain how deaths are related to the reported adverse-event categories. The serious-event terms are reported with percentages, but further context is not reported in the registry record. These omissions constrain interpretation of the safety profile.

Results for the listed secondary outcomes are not reported in the registry record. It also does not report confidence intervals, hypothesis tests, the detailed statistical analysis plan, missing-data methods, multiplicity procedures, interim analyses, or a sample-size justification. The record lists zero analyses, which leaves the methods behind any analyses unavailable rather than establishing that no analyses occurred.

Finally, the primary safety population is defined as participants who received at least one dose, while the adverse-event group lists 26 at risk. The registry record does not give participant-level data or additional population details that would permit evaluation of follow-up completeness, overlap across outcomes, or the effect of missing information. These reporting limitations should be considered alongside the descriptive counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Abemaciclib Plus Ramucirumab for Esophageal/Gastroesophageal Junction Ca — NCT04921904.
• Registry record last updated 2026-09-14; status last verified 2026-08.
• Results first posted 2026-09-14.
• 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.

19. Record Summary

NCT04921904 is a completed Phase I/II, single-group study of abemaciclib plus ramucirumab in metastatic esophageal or gastroesophageal junction adenocarcinoma. The registry lists enrollment of 26, no masking, and allocation as not applicable. Treatment is described as abemaciclib 150mg orally twice daily every day with ramucirumab 8mg/kg intravenously every 2 weeks.

The primary outcome is safety, defined around counts of participants experiencing adverse events and serious adverse events of Grade 3 or higher using CTCAE v4.0. The posted group counts include 6 participants with serious adverse events and 17 with other adverse events, with 26 at risk in each category. The record also lists 11 deaths and six serious-event terms, each reported as 3.8%.

The registry names objective response rate, progression free survival, overall survival, and rate of stable disease as secondary outcomes, but their results are not reported in the registry record. No randomized comparator or detailed analysis plan is reported. The safety figures are therefore descriptive, with no basis for a controlled treatment-effect conclusion.