ABEMA Alone or in COMBO With MK-6482: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ABEMA Alone or in COMBO With MK-6482 (NCT04627064), a non-randomized phase 1 study. The primary outcome is Objective Response Rate (ORR) in Abemaciclib Arm (Arm 1).

2. Clinical Question

3. Trial Design

This was a Phase I trial with sequential enrollment and non-randomized allocation. The registry record identifies Dana-Farber Cancer Institute as the sponsor and reports the study as completed. Enrollment was 11 participants. The study start date was 2020-12-31, and primary completion was 2024-02-09.

The study included an abemaciclib-alone arm and an abemaciclib-plus-MK-6482 arm. The combination arm was to begin enrolling only after experience had been gained with abemaciclib alone. Its dose escalation was described as following a 3+3 design. The available arm descriptions are incomplete, so further operational details are not reported in the registry record.

The study was open-label, with no masking. The primary endpoint was objective response rate in the abemaciclib arm. The registry defines response as complete or partial response by RECIST 1.1, determined by central review. It also lists safety outcomes for the combination arm and duration of response, progression-free survival, and overall survival in both arms.

Because allocation was not randomized and enrollment was sequential, comparisons between arms would be vulnerable to differences in who entered each arm and when. The registry record itself states that the arms are not a like-for-like control comparison. The study therefore should not be interpreted as a randomized estimate of the relative effects of the two regimens. The record does not report a formal statistical analysis plan, a sample-size justification, or interim-analysis details.

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: The analysis dataset is comprised of all treated 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.

Population: Arm1 included 11 patients enrolled on the study and receiving protocol treatment. Arm 2 never opened.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR) in Abemaciclib Arm (Arm 1), measured over From the start of protocol treatment until disease progression or deaths. The total duration assessed was up to 3 months, as all patients either progressed, died, or withdrew from the study within that timeframe..

The primary endpoint is objective response rate (ORR) in the abemaciclib-alone arm. It is defined as the percentage of patients whose best overall response is complete response (CR) or partial response (PR), using RECIST 1.1 and central review. The analysis population is described as all treated participants. Imaging was scheduled every 8 weeks during the first six months and every 12 weeks thereafter.

ORR is a binary endpoint at the participant level: each participant either meets the response definition or does not. A response measure can describe the proportion of treated participants who experienced tumor shrinkage meeting the stated criteria. The definition makes the response categories and assessment approach explicit, while central review is the registry-stated method for determining response.

The reported assessment timeframe runs from the start of protocol treatment until disease progression or death. The record says the total duration assessed was up to 3 months because all patients either progressed, died, or withdrew within that timeframe. The registry does not report the number of complete or partial responses, the ORR estimate, or its precision. As a result, the endpoint definition is available, but its observed result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a participant count for a binary event: meeting the definition of objective response or not meeting it. The registry defines a response as complete or partial response according to RECIST 1.1, determined by central review. The endpoint is named as a rate, but a rate requires a numerator—the number of responders—and a denominator—the number included in the analysis. The record describes the primary analysis population as all treated participants, but does not report the response count or rate. Those results are not reported in the registry record.

What does a binary endpoint represent?

A binary endpoint classifies each participant into one of two categories. For ORR, the categories are response and no response under the stated criteria. A count can be useful for describing the observed number meeting the response definition. A proportion places that count in relation to the analysis population. The proportion is an estimate for the studied group, not a guarantee that the same value would occur in another group. Its precision depends on the number of participants and the observed event count.

A confidence interval is a general statistical tool that expresses uncertainty around an estimated quantity. In repeated studies under the method's assumptions, a confidence-interval procedure is designed to cover the underlying quantity at its stated level at a specified frequency. A narrow interval indicates greater precision than a wide interval, while neither interval establishes causation or eliminates design limitations. Here, the registry record does not report a primary ORR estimate or interval, so no trial-specific precision statement can be made.

How does the design affect interpretation?

Allocation was non-randomized, masking was absent, and enrollment was sequential. In a randomized comparison, allocation by chance is intended to balance prognostic factors on average across groups. That protection is not present in a non-randomized design. Sequential enrollment can also mean that participants in one arm entered under different circumstances from those in another. Thus, any between-arm difference would be descriptive unless adequately supported by a suitable analysis and design; the registry specifically cautions that the arms are not a like-for-like control comparison.

The combination arm's dose escalation was described as a 3+3 design. This is a dose-escalation approach, but the registry record does not report the detailed dose-limiting toxicity definition, escalation decisions, or results. It also does not report the trial's statistical analysis plan, a sample-size justification, or interim-analysis procedures. These details should not be inferred from the phase or design labels.

What do the listed outcomes contribute?

Duration of response describes how long a response lasts among participants who achieve an objective response. Progression-free survival and overall survival are time-to-event outcomes. The registry lists these outcomes for both arms, as well as treatment-related adverse events for the combination arm. Listing an outcome states that it was planned or collected as an outcome measure; it does not itself give an estimate. The record reports 0 analyses, and specific results for these listed measures are not reported in the registry record.

Time-to-event methods generally account for the time until an event and may also account for participants whose event has not been observed by the end of follow-up. This is general statistical context, not a description of the analysis used in this trial. The registry does not report the methods used for censoring, survival estimation, or comparisons. The primary endpoint timeframe is described separately: follow-up for that assessment ran from treatment start until progression or death, and total assessment was up to 3 months because all patients progressed, died, or withdrew within that timeframe.

How should planning illustrations be read?

Sample-size calculations are planning tools, not trial outcomes and not observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustration is based on a total number of events; for other outcomes, it is expressed as participants per arm. These are illustrative assumptions, not evidence that the trial was designed or conducted that way. The registry record does not report a trial-specific sample-size justification. Without a reported primary response estimate, the observed effect and any trial-specific planning implication cannot be described.

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-Arm 1")
n      <- c(11)
events <- c(0)
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-Arm 1  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary ORR outcome, safety, duration of response, progression-free survival, and overall survival. Assessing multiple outcomes can raise multiplicity concerns: when many hypotheses are tested, the chance of at least one apparently notable result can increase. General approaches include identifying a primary hypothesis in advance, adjusting for multiple tests, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy or statistical analysis plan, so it is not possible to determine how multiple outcomes were handled.

The registry reports 0 analyses. It does not report a primary response count, response rate, confidence interval, or p-value. Outcome-specific estimates for the listed secondary measures are not reported in the registry record. Absence of a reported analysis is not evidence of no events or no response; it means the corresponding results cannot be assessed from the record.

The primary analysis population is described as all treated participants. The available information does not explain how missing response assessments, withdrawals, or other incomplete observations were handled. The endpoint timeframe states that all patients either progressed, died, or withdrew within up to 3 months, but does not provide the number in each category or clarify their endpoint classification. Missing-data assumptions and sensitivity analyses are not reported in the registry record.

These gaps matter because endpoint estimates can depend on who is included and how incomplete observations are treated. The reported analysis population provides a broad definition, but it does not supply the operational rules needed to reproduce the analysis. No imputation method, censoring rule, or adjustment method should be assumed.

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: back pain (9.1%).

For the abemaciclib-alone arm, the registry reports 11 participants at risk for serious adverse events and 1 affected participant. It also reports 11 participants at risk for other adverse events and 11 affected participants. The record lists 9 deaths. These are counts as recorded; the available information does not establish whether the deaths or individual adverse events were caused by study treatment.

Back pain is listed among the top serious-event terms at 9.1%. That term-level figure should be read as a registry-reported safety entry, not as a complete account of severity, timing, duration, recurrence, or causality. The record does not provide event-level narratives or further attribution details in the available information.

Counts and percentages answer different descriptive questions, and neither alone establishes a treatment effect. The study was non-randomized and had 11 participants overall, so the safety figures should be read as observations in this study rather than as a controlled estimate of comparative risk. The registry also lists treatment-related adverse events for the combination arm as an outcome, but the specific combination-arm safety results are not reported in the registry record.

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

This study addresses an early-phase question about abemaciclib alone and in combination with MK-6482 in advanced ccRCC. Its registry record defines a primary endpoint—objective response in the abemaciclib-alone arm—and gives the response criteria and assessment process. It also identifies safety and time-to-event outcomes. These details clarify what the study set out to assess.

The record does not report the primary response count or rate, nor does it report analyses for the listed outcomes. Consequently, it does not establish the observed response result or its precision. The reported design, outcome names, and assessment schedule cannot fill that gap. A response estimate and its uncertainty would be needed to describe the primary result statistically.

The study does not provide a randomized comparison between the two regimens. The arms were non-randomized and sequential, and the registry explicitly says they are not a like-for-like control comparison. Any apparent difference between arms would therefore not, by itself, identify a treatment effect. The registry record does not report a comparative analysis that could address this limitation.

The safety counts describe events recorded in the abemaciclib arm, including serious events, other events, and deaths. They do not by themselves determine whether an event was caused by treatment. The combination-arm adverse-event result is not reported in the registry record. These counts should be understood in the context of the small overall enrollment and the absence of randomized allocation.

In short, the record supports a description of the trial design, endpoint definitions, and selected safety counts. It does not support a quantitative conclusion about the primary response outcome or a causal comparison of the regimens. Missing statistical results are not evidence that the treatments had no effect; they mean that the relevant effect estimates cannot be assessed from the registry record.

14. Why This Trial Matters Statistically

Early-phase trials often combine questions about safety, dose escalation, and preliminary activity. This study's record reflects that broad scope: it describes abemaciclib alone and in combination with MK-6482, lists a dose-escalation approach for the combination arm, and names response, safety, and time-to-event outcomes. Understanding which question each measure addresses helps prevent safety observations or outcome definitions from being mistaken for evidence of efficacy.

The design is also statistically important. Sequential, non-randomized enrollment is different from a randomized trial, particularly when readers are tempted to compare outcomes between arms. The registry explicitly cautions that these arms are not like-for-like controls. That distinction matters because a numerical difference across groups can reflect selection or timing as well as treatment.

The primary endpoint is defined with explicit response criteria and central review, which clarifies how response was intended to be classified. At the same time, a clearly defined endpoint is not the same as a reported result. The registry record does not report the response count or rate, and it reports 0 analyses. This separates the question the study set out to answer from what can be concluded from its posted results.

Finally, the safety entries illustrate why counts need context. The reported figures are descriptive observations in a small, non-randomized study; they do not independently establish causality or comparative risk. Reading the design, endpoint definition, analysis availability, and safety counts together gives a more disciplined account of what the record can and cannot establish.

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 ORR count or estimate, despite defining the endpoint and analysis population. It also reports 0 analyses, so precision estimates and inferential results are not available for the listed outcomes. The record therefore does not permit a quantitative assessment of the primary endpoint.

Enrollment was 11 overall, and allocation was non-randomized. Enrollment was sequential, with the combination arm beginning only after experience with abemaciclib alone. The registry says the arms are not a like-for-like control comparison. These features limit the interpretation of any between-arm comparison and restrict the extent to which findings can be generalized.

The endpoint timeframe was up to 3 months because all patients progressed, died, or withdrew within that timeframe. The record does not report how many participants fell into each category, how withdrawals were handled in the primary analysis, or how incomplete assessments were classified. Details about missing-data methods, censoring, and sensitivity analyses are not reported in the registry record.

The available arm descriptions are incomplete, and the registry does not report the statistical analysis plan, trial-specific sample-size justification, or interim-analysis procedures. Although a 3+3 design is named for combination-arm dose escalation, the dose-escalation decisions and results are not reported in the available information. The safety counts also lack event-level timing and attribution detail, and combination-arm safety results are not reported. These gaps limit reproducibility and prevent a fuller evaluation of benefit, risk, and uncertainty.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: ABEMA Alone or in COMBO With MK-6482 — NCT04627064.
• Registry record last updated 2025-07-25; status last verified 2025-07.
• Results first posted 2025-07-25.
• 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

The registry record describes a completed, Phase I, non-randomized, open-label, sequential trial of abemaciclib alone or with MK-6482 in advanced clear cell renal cell carcinoma. Enrollment was 11. The primary endpoint was objective response rate in the abemaciclib-alone arm, defined by complete or partial response under RECIST 1.1 with central review. The record reports selected abemaciclib-arm safety counts, including 1 participant with a serious adverse event, 11 with other adverse events, and 9 deaths. It reports 0 analyses; the primary response result and specific analyses of the listed secondary outcomes are not reported in the registry record. The arms are not randomized and are not a like-for-like control comparison.