A Study of LY2940680 in Japanese Participants With Advanced Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of LY2940680 in Japanese Participants With Advanced Cancers (NCT01919398), a na phase 1 study. The primary outcome is Number of Participants With LY2940680 Dose-Limiting Toxicities (DLT).

2. Clinical Question

3. Trial Design

This was a Phase 1, single-group study of LY2940680 in Japanese participants with advanced solid cancers. The registry record lists an enrollment of 19, a start date of 2013-08, a primary completion date of 2016-05, and a completed status. Eli Lilly and Company is listed as the sponsor. The registered condition is Neoplasm Metastasis.

The intervention was LY2940680, administered orally each day in 28-day cycles. Three dose cohorts are described: 100 mg, 200 mg, and 400 mg. The record says treatment continued until disease progression, unacceptable toxicity, or another stopping condition, but the final wording in the arm description is incomplete. Further treatment rules are not reported in the registry record.

The design is recorded as single group, with allocation listed as not applicable and masking as none. There was no randomized control group. Cohorts receiving different doses do not provide a randomized, like-for-like comparison: dose assignment procedures and cohort comparability are not reported in the registry record. Any apparent differences between cohorts would therefore be descriptive and could reflect factors other than dose.

The primary outcome was the number of participants with dose-limiting toxicities during Cycle 1 (28 Days). The defined population was all participants who received at least one dose of study drug. Listed secondary outcomes cover pharmacokinetic measures, overall response, and change in Hedgehog-regulated gene expression in skin. The registry record does not report outcome results or statistical analysis entries, so the design and planned outcome domains can be described, but effects and their precision cannot be evaluated from these results.

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: Study completers were participants who were Dose-Limiting Toxicities (DLT) evaluable and discontinued the treatment due to any reason.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug.

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: All participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With LY2940680 Dose-Limiting Toxicities (DLT), measured over Cycle 1 (28 Days).

The primary endpoint counts participants with a dose-limiting toxicity, or DLT, during Cycle 1 (28 Days). The registry record defines a DLT as an adverse event during that cycle that was possibly related to study drug and met at least one specified criterion based on NCI CTCAE, version 4.0. The criteria encompass severe nonhematological toxicity, selected symptoms that persist despite supportive care, specified blood-count and liver-enzyme toxicities, febrile neutropenia, and toxicity requiring a prolonged dose omission or otherwise judged dose limiting by the primary investigator and sponsor.

A count of participants meeting a DLT definition is used in early-phase safety assessment because it records how many treated participants met the protocol’s toxicity criteria during the specified observation period. This endpoint is not a general measure of every adverse event, nor does it capture the full range of later treatment experiences. Its interpretation depends on the definition, attribution, observation window, and analysis population.

The registry record specifies the Cycle 1 window and defines the population as participants who received at least one dose. It does not report the number meeting the DLT definition, a percentage, a confidence interval, or details of adjudication. Consequently, the primary endpoint can be described, but the observed DLT frequency and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the single-group design permit?

The registry record describes a single-group study with no masking and allocation listed as not applicable. Participants were treated in dose cohorts, but the record does not describe a randomized allocation process. General statistical point: a randomized comparison aims to balance prognostic characteristics across treatment groups, on average, so observed outcome contrasts can be interpreted with a clearer causal basis. In a nonrandomized dose-cohort study, group differences may reflect participant characteristics, timing, clinical decisions, or other factors as well as dose.

For that reason, cohort-specific counts are best read as descriptive summaries. They can document the number of participants recorded as affected in each cohort, but they cannot by themselves estimate the causal effect of one dose relative to another. The registry record does not report a control arm, an adjustment strategy, or a formal between-cohort analysis. Such methods should not be assumed.

What does a participant count convey?

The primary endpoint is a count of participants with a DLT during Cycle 1 (28 Days), among participants who received at least one dose. A count is a direct summary of how many people met the endpoint definition. General statistical point: a count depends on the number of people observed as well as the number meeting the event definition. A count alone does not convey how precisely the underlying event frequency is estimated; denominators and an uncertainty interval are needed for that assessment.

The registry record gives the endpoint definition and population but does not post the primary DLT count or a corresponding denominator for the endpoint result. Therefore, neither the observed event frequency nor its uncertainty can be reconstructed from the primary-outcome information recorded in the results. The serious adverse-event counts are a separate safety summary and should not be substituted for the DLT endpoint, which has its own criteria and observation window.

How should uncertainty be understood?

General statistical point: a confidence interval describes a range of values that are reasonably compatible with the observed data under a specified statistical procedure. A wider interval indicates less precision; a narrower interval indicates greater precision, conditional on the procedure and its assumptions. An interval is not a guarantee that a particular value is true, and its interpretation depends on how the data were collected and analyzed.

No confidence interval for the primary outcome or the posted serious adverse-event counts is reported in the registry record. The cohort counts are therefore not accompanied by a direct measure of sampling uncertainty. In a study with small cohorts, each participant’s status can materially affect a descriptive count, but no numerical uncertainty measure should be inferred when one is not reported.

Why do event definitions and observation periods matter?

The DLT endpoint applies a specified set of clinical criteria during Cycle 1 (28 Days). It includes selected severe toxicities, some duration-based criteria, and investigator and sponsor judgment for certain dose-limiting events. General statistical point: a carefully defined endpoint supports consistent classification, but its meaning is specific to that definition. A DLT count is not equivalent to a count of all adverse events, and a Cycle 1 result would not describe toxicity occurring outside that interval.

Interpretation also depends on attribution: the endpoint definition requires an adverse event to be possibly related to study drug. The registry record does not report details of how attribution was determined, how borderline cases were handled, or whether outcome assessment was independently reviewed. Those procedures are not reported in the registry record and cannot be inferred from the endpoint wording alone.

What is reported about analysis?

The registry record lists no analysis entries. It does not report an inferential statistical method, an effect estimate, a confidence interval, a hypothesis test, or a model for the primary endpoint. It also does not report whether interim analyses were conducted or give a sample-size justification. These omissions do not establish that no additional analysis occurred; they mean the analysis details are not reported in the registry record.

General statistical point: an analysis plan specifies how outcomes are summarized, how uncertainty is quantified, which populations are included, and how multiple outcomes or comparisons are handled. Without that information, readers cannot determine whether a posted estimate was adjusted, which assumptions were used, or how analysis decisions were made. Since no primary-outcome result is posted, there is no basis for recalculating that result from summary statistics.

How do the other outcome domains fit?

The listed secondary outcomes address pharmacokinetics, tumor response, and a pharmacodynamic measure. Maximum concentration and area under the concentration-time curve describe aspects of drug exposure; overall response rate counts participants with complete or partial response; and percentage change from baseline in skin Gli1 expression concerns a molecular measure. These outcomes address different questions and use different types of data. The registry record does not report their results or their analysis methods.

General statistical point: distinct outcomes may have different measurement scales, observation windows, and sources of uncertainty. Their estimates should not be treated as interchangeable evidence. The registry record does not report how missing measurements, repeated observations, or multiple outcome testing were handled. No specific handling method should be assumed.

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("Cohort 1: 100 mg LY2940680", "Cohort 2: 200 mg LY2940680", "Cohort 3: 400 mg LY2940680")
n      <- c(3, 3, 13)
events <- c(0, 0, 3)
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  Cohort 1: 100 mg LY2940680  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 2: 200 mg LY2940680  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 3: 400 mg LY2940680  13  3  23.1  5.0  53.8  8.2  50.3  8.4  50.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary DLT endpoint and secondary outcomes covering pharmacokinetics, overall response, and skin gene expression. It does not report a multiplicity strategy, such as a hierarchy of hypotheses, an adjustment to significance thresholds, or a designation of which secondary outcomes were intended as confirmatory. The record lists no analysis entries. Therefore, it is not possible to determine whether or how the chance of false-positive findings across multiple outcomes was addressed.

General statistical point: when several hypotheses are tested, the chance of at least one apparently unusual result can increase if each is judged independently using the same decision rule. A prespecified strategy can clarify which findings are primary and how secondary results should be interpreted. Without a reported strategy or analysis results, no claim about statistical significance across outcomes can be evaluated for this study.

Missing-data methods are not reported in the registry record. The primary endpoint population is defined as all participants who received at least one dose, but the record does not describe whether every such participant completed the Cycle 1 assessment, how incomplete assessments were treated, or how missing secondary measurements were handled. The number or pattern of missing outcome data is also not reported in the registry record.

The analysis population for the primary endpoint is specified by the registry definition, but the record does not give a separate analysis-population flow or confirm how many enrolled participants received treatment and contributed endpoint data. No imputation, exclusion, or sensitivity-analysis method should be presumed. These omissions limit assessment of whether the posted summaries represent all eligible observations and how robust any result might be to incomplete data.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: thrombocytopenia (7.7%), pericardial effusion (7.7%), pyrexia (7.7%), decreased appetite (7.7%), cerebral infarction (7.7%).

The registry record lists serious adverse-event figures separately for each dose cohort. In the 100 mg cohort, 0 participants were affected among 3 at risk; in the 200 mg cohort, 0 were affected among 3 at risk; and in the 400 mg cohort, 4 were affected among 13 at risk. These are descriptive counts, not a controlled comparison. The record does not report confidence intervals or an inferential analysis for these figures.

The listed serious-event terms are Thrombocytopenia, Pericardial effusion, Pyrexia, Decreased appetite, Cerebral infarction, and Cerebrovascular accident, each recorded as 7.7%. The summary does not establish whether participants experienced more than one listed term; the terms should not be summed to infer a number of affected people. Deaths are not reported in the registry record.

The registry also lists participants affected in the other-adverse-event category: 3 of 3 in the 100 mg cohort, 3 of 3 in the 200 mg cohort, and 13 of 13 in the 400 mg cohort. Those counts are distinct from the serious-event figures and from the primary DLT endpoint. The registry record does not provide enough detail in this summary to characterize the other events’ severity, duration, or relationship to treatment.

General statistical point: safety summaries describe events observed in the recorded study population, but the counts alone do not establish whether an event was caused by treatment. The single-group design, limited cohort sizes, and absence of a control arm constrain comparisons.

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

The registry record documents a Phase 1 study designed to assess LY2940680 safety and tolerability in Japanese participants with advanced solid cancers. It identifies the dose cohorts, the Cycle 1 DLT definition, and selected safety counts. Those details describe the study’s structure and the safety information posted in the record; they do not provide the primary DLT result or a complete statistical assessment.

The serious adverse-event summary records affected participants in each cohort, along with several event terms. These counts do not show whether differences between dose cohorts are due to dose. There is no randomized control group, and no adjustment or comparative analysis is reported. The data also do not establish the likelihood of an event in a broader population, particularly because the cohort counts are limited and no uncertainty intervals are posted.

The record’s stated primary purpose concerns safety and tolerability up to the global recommended dose. However, the primary outcome count is not reported in the registry record, and the record does not report a recommended-dose conclusion. It is therefore not possible to determine from the posted results how many participants met the DLT definition or how precisely that outcome was estimated.

The listed secondary outcomes could address drug exposure, response, and pharmacodynamic change, but their results are not reported in the registry record. No conclusions about pharmacokinetics, tumor response, or gene-expression change can be drawn from their names alone. Likewise, the safety counts should not be interpreted as evidence that treatment did or did not cause particular events.

General statistical point: an absence of a reported estimate is not the same as an estimate of no effect or no risk. A result requires outcome data and an analysis; its precision requires an uncertainty measure or enough information to calculate one appropriately. In this record, the primary result and inferential analyses are not posted. The defensible interpretation is consequently limited to the design, endpoint definition, and descriptive safety information that the registry record reports.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a registered clinical question and a result that can be statistically interpreted. The registry record clearly identifies a Phase 1 safety and tolerability objective, dose cohorts, and a primary DLT endpoint with a defined observation period. Yet the primary endpoint result and analysis details are not reported in the registry record. Without them, the central safety outcome cannot be quantified or assessed for precision.

The single-group design is also important to interpretation. Dose cohorts can organize safety observations across planned dose levels, but they do not function as randomized controls. Descriptive counts are useful for recording what was observed in the enrolled groups; they do not isolate a dose effect or establish a causal contrast. This distinction matters whenever cohort summaries might otherwise be read as comparisons.

The record further shows why outcome definitions and populations need to be kept distinct. A DLT is defined using particular criteria in Cycle 1 (28 Days), while the serious adverse-event summary and other-adverse-event summary use their own categories. They answer related but not identical questions. One category cannot stand in for another, and event terms should not be combined without information about overlap.

General statistical point: estimates are most informative when accompanied by a clear denominator, uncertainty measure, analysis population, and analysis method. The posted serious-event counts have cohort denominators but no reported confidence intervals or inferential comparison. For the primary endpoint, even the result count is not reported. This limits not only causal interpretation but also assessment of statistical precision.

The study is therefore a useful example of why registry design details and registry results must be read separately. The design describes the question that was posed; the posted results determine what can be concluded from the observed data. Here, the former is described more fully than the primary outcome analysis.

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.

Several limitations specific to this study constrain interpretation. The registry record describes a single-group design and no masking, with no randomized control arm. The cohorts receiving 100 mg, 200 mg, and 400 mg cannot be treated as comparable groups for causal dose comparisons. Cohort assignment procedures and baseline characteristics are not reported in the registry record, so potential differences between cohorts cannot be assessed.

The primary outcome, number of participants with DLT during Cycle 1 (28 Days), is defined, but its result is not reported in the registry record. No confidence interval or analysis method is reported. This prevents assessment of the observed primary safety outcome and its precision. The serious adverse-event counts are posted by cohort, but no uncertainty intervals or formal comparison are provided.

The registry record does not report a sample-size justification, interim-analysis approach, statistical analysis plan, missing-data methods, or multiplicity strategy. It also does not report results for the listed pharmacokinetic, response, and pharmacodynamic outcomes. These omissions leave uncertainty about analysis decisions and the completeness of the outcome evidence available in the record.

The treatment description states that therapy continued until disease progression, unacceptable toxicity, or another condition, but the final wording is incomplete. The duration and stopping rules beyond the reported wording are therefore not fully described. Deaths are not reported in the registry record. The posted safety summaries also do not establish event overlap among the listed serious-event terms or provide further detail about the other-adverse-event category. These limitations narrow the conclusions that can be drawn from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of LY2940680 in Japanese Participants With Advanced Cancers — NCT01919398.
• Registry record last updated 2019-09-11; status last verified 2019-08.
• Results first posted 2019-09-11.
• 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

NCT01919398 is a completed Phase 1, single-group study of LY2940680 in Japanese participants with advanced solid cancers. The registry record lists enrollment of 19, a start date of 2013-08, and a primary completion date of 2016-05. The study included cohorts receiving 100 mg, 200 mg, or 400 mg orally each day in 28-day cycles, with no masking and no control arm.

The primary endpoint was the number of participants with dose-limiting toxicity during Cycle 1 (28 Days), among participants who received at least one dose. The DLT definition is described, but its result is not reported in the registry record. Serious adverse-event counts are listed by cohort, as are other-adverse-event counts and serious-event terms. Results for the listed pharmacokinetic, response, and skin gene-expression outcomes are not reported in the registry record. The record lists no analysis entries, and inferential methods, missing-data handling, multiplicity procedures, and sample-size justification are not reported.