A Study of IMC-TR1 in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of IMC-TR1 in Participants With Advanced Solid Tumors (NCT01646203), a registered phase 1 study. The primary outcome is Number of Participants With Dose-Limiting Toxicities (DLTs).

2. Clinical Question

This was a phase 1 study of IMC-TR1 in participants with advanced solid tumors. Its stated aims were to evaluate safety and tolerability and to gather evidence of antitumor activity. The study title describes patients whose tumors had failed standard therapy or for whom no standard was available. The registry lists neoplasms and tumor as conditions.

The primary question is about dose-limiting toxicities, or DLTs, in the initial treatment period. The endpoint counts participants, rather than counting every toxicity episode. It therefore addresses how many people met the study's DLT definition during that period. The definition required an event in Cycle 1 that was considered at least possibly related to study drug, dose-dependent, and within specified toxicity criteria.

Other listed outcomes included maximum tolerated dose, DLT counts, development of antibodies against IMC-TR1, response by RECIST version 1.1, and pharmacokinetic measures. These outcomes cover dose finding, safety, immune response, tumor measurement, and drug concentrations. Their results are not reported in the registry record. The registry's stated aims and outcome list should not be mistaken for evidence that any particular effect was observed.

3. Trial Design

The registry identifies this as a phase 1, sequential study with no masking. It records an enrollment of 14 and a status of completed. The recorded start was 2012-07, and primary completion was 2014-10. The sponsor was Eli Lilly and Company. These registry entries describe the study framework; they do not provide a participant flow account or establish how many participants received each dose.

The intervention was IMC-TR1. The arm description identifies Cohort 1A as receiving 1.25 mg/kg intravenously every 2 weeks of a 6-week treatment cycle. Cohorts 1B-9 are described as dose escalation from 12.5 mg to 1600 mg as a flat dose, intravenously every 2 weeks of the 6-week treatment cycles. The record also begins a description of dose escalation from 800 mg to 1600 mg for Cohorts 10-12, but that description is incomplete in the registry record. More detail about the doses or schedules for those cohorts is not reported in the registry record.

Sequential dose escalation differs from a randomized comparison. Participants are grouped by dose cohort, and the registry does not identify a separate control arm. Allocation is not stated, so the relationship between a participant's characteristics, timing, and dose group cannot be assessed from this information. The listed dose groups are not a like-for-like control comparison. Differences in their event counts should not be read as randomized treatment effects.

The registry lists nine outcome measures and zero analyses. A statistical analysis plan, dose-escalation decision rules, and sample-size justification are not reported in the registry record. The study design label alone does not establish how doses were selected, what stopping criteria were used, or whether any interim analyses took place.

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: Participants that completed Cohort 1A, Cohort 1B or Cohort 2 are those who died, had progressive disease (PD) or off treatment \& censored due to study completion.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose-Limiting Toxicities (DLTs), measured over First Dose Up to 6 Weeks.

The primary endpoint is the number of participants with dose-limiting toxicities from the first dose up to 6 weeks. It is a count of participants meeting the DLT definition during the specified observation period, not a count of all adverse events and not a measure of tumor response.

The registry defines a DLT as an adverse event occurring during Cycle 1, the first 6 weeks of treatment, that was considered at least possibly related to study drug, considered dose-dependent, and met a selected toxicity criterion. The criteria refer to NCI-CTCAE version 4.0 and include specified severe nonhematological or hematological toxicities, cardiac findings, life-threatening toxicity, and major ocular events. The full definition in the registry contains multiple specific criteria; interpretation of a counted DLT depends on applying those criteria and the stated relatedness and dose-dependence judgments.

A DLT endpoint is used in early dose-finding research because it focuses on important toxicities observed during an initial treatment window. Counting participants makes the outcome clinically interpretable as the number who met the endpoint, while the defined time window makes clear which treatment period is being assessed. It does not describe every safety event over the entire study or establish longer-term safety.

The registry record does not report the observed primary endpoint count, nor does it provide a result by dose cohort. The endpoint definition and its purpose can therefore be described, but the incidence of DLTs in this study cannot be stated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level event summarized as a count: a participant either met the DLT definition during the specified period or did not. The reported unit is participants. This differs from an event count, because one participant could experience more than one qualifying toxicity while still contributing as one participant with a DLT. The registry record does not report the observed primary count, so no event proportion can be stated.

Why define a specific observation window?

The first-dose-to-6-week window anchors the primary endpoint to the first treatment period, identified in the registry as Cycle 1. A fixed observation window is important because the chance of observing an event can depend on how long participants are followed. A count over one period is not directly interchangeable with a count over a longer or differently defined period. This endpoint does not, by itself, summarize toxicities occurring after the first 6 weeks.

The DLT definition also requires judgments about timing, relationship to study drug, dose dependence, and clinical criteria. Those conditions distinguish the primary endpoint from a count of every adverse event. The criteria reference NCI-CTCAE version 4.0 and include several categories of serious toxicity. The registry provides the definition but does not report case-level information, adjudication details, or the number of participants meeting each criterion.

What do group counts communicate?

A count of participants with an event is most informative when considered with the number of participants assessed. The adverse-event information gives at-risk and affected counts for each of three dose groups. The registry reports 0 serious events among 2 at risk and 2 other events among 2 at risk for 1.25 mg/kg LY3022859; 2 serious events among 5 at risk and 4 other events among 5 at risk for 12.5 mg LY3022859; and 4 serious events among 7 at risk and 7 other events among 7 at risk for 25 mg LY3022859. These are descriptive counts for those groups, not estimates from a randomized comparison.

General statistical principle: when group sizes are small, one participant's outcome can noticeably change a count-based estimate. Confidence intervals, when available, communicate uncertainty around an estimate; a wider interval indicates less precision. The registry record does not report confidence intervals for these adverse-event counts. No confidence interval should be inferred from the counts alone in this explanation.

Why not compare these groups as if randomized?

The registry characterizes the study as sequential and says that allocation is not stated. There is no stated randomized control group. In a randomized comparison, allocation is designed to make treatment groups comparable on average, subject to chance. That design feature is not reported. In a sequential dose-escalation study, dose groups can also reflect different points in the study's dose sequence. The posted counts therefore describe outcomes in the listed groups, but do not isolate a causal dose effect.

General statistical principle: comparisons can be confounded when groups differ in ways associated with both the exposure and outcome. Without details about allocation, participant characteristics by dose, timing, or the dose-escalation rules, it is not possible to determine whether observed group differences reflect dose, participant mix, chance, or other factors. Adjustment could address some measured differences in an appropriate dataset, but an adjusted analysis is not reported in the registry record.

What do the planning assumptions mean?

The record describes sample-size planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The targeted effect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not the trial's own design rationale and not observed power. The registry record does not report the trial's sample-size justification. The equal-allocation assumption also does not describe the listed sequential dose-escalation cohorts or establish that participants were allocated equally between two groups.

General statistical principle: power calculations depend on assumptions about the effect to detect, variability or event frequency, significance threshold, and allocation. A planning calculation cannot show that a completed study had a particular probability of detecting an effect after results are known. Because no primary endpoint result or sample-size illustration values are reported in the registry information, no numerical planning estimate can be interpreted.

What does the analysis record establish?

The registry lists zero analyses. It does not report an inferential model, hypothesis tests, confidence intervals, covariate adjustment, or a method for handling repeated events. The primary endpoint's count format alone does not identify a statistical model. Likewise, listing a response outcome assessed by RECIST version 1.1 does not reveal how response was summarized or whether an analysis was performed. The safest statistical reading is to distinguish the endpoint definitions and descriptive safety counts that are recorded from analyses and results that are 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("1.25 mg/kg LY3022859", "12.5 mg LY3022859", "25 mg LY3022859")
n      <- c(2, 5, 7)
events <- c(2, 0, 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  1.25 mg/kg LY3022859  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  12.5 mg LY3022859  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  25 mg LY3022859  7  2  28.6  3.7  71.0  8.2  64.1  8.5  65.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including the primary DLT count and secondary outcomes covering maximum tolerated dose, DLTs, immunogenicity, response, and pharmacokinetics. It lists zero analyses. No multiplicity strategy is reported in the registry record. It is therefore not possible to tell whether hypotheses were prespecified for formal testing, whether any adjustment for multiple outcomes was planned, or how any exploratory results would have been distinguished from confirmatory findings.

General statistical principle: when multiple outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. A multiplicity plan may define which outcomes are primary, how tests are ordered, or how error rates are controlled. The registry's designation of a primary endpoint identifies its stated primary outcome, but does not by itself show what inferential procedures were used.

The registry defines the primary endpoint population as participants who received at least one dose of study drug. The number of participants meeting that definition is not reported in the registry record. The record also does not describe missing endpoint data, exclusions from the analysis population, censoring, or methods for handling participants whose DLT status could not be established. The enrollment figure alone does not resolve these questions.

Information about missing data is important because incomplete follow-up can affect who contributes to an endpoint summary. General statistical principle: the consequences depend on why data are missing and how the analysis handles them. Without participant-level follow-up information and a stated missing-data approach, the direction or magnitude of any potential effect cannot be assessed. No imputation or sensitivity analysis is reported in the registry record.

The registry does not report a statistical analysis plan, interim analyses, or a sample-size justification. These items are not recoverable from the outcome definitions alone. Accordingly, no claim about multiplicity control, missing-data handling, or analysis-population choices beyond the stated primary population definition is warranted.

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: dehydration (28.6%), intestinal obstruction (20.0%), small intestinal obstruction (20.0%), retroperitoneal haemorrhage (14.3%), infusion related reaction (14.3%).

The registry reports serious and other adverse-event participant counts for three dose groups. In the 1.25 mg/kg LY3022859 group, 0 of 2 participants at risk had a serious event, and 2 of 2 had an other event. In the 12.5 mg LY3022859 group, 2 of 5 had a serious event, and 4 of 5 had an other event. In the 25 mg LY3022859 group, 4 of 7 had a serious event, and 7 of 7 had an other event. These counts describe participants recorded as affected, not the number of separate events.

The serious-event terms with listed percentages are dehydration, 28.6%; intestinal obstruction, 20.0%; small intestinal obstruction, 20.0%; retroperitoneal haemorrhage, 14.3%; infusion related reaction, 14.3%; and syncope, 14.3%. The registry record does not give the term-specific participant counts in the information. Terms may overlap within participants, so their percentages should not be added or treated as separate groups.

The at-risk groups are small, and the study was sequential rather than a randomized comparison. These summaries do not establish that a dose caused an event or that one dose group had greater risk than another. Death counts are not reported in the registry record. The adverse-event summaries also do not replace the primary DLT result, which is not reported in the registry record.

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

The posted information documents a phase 1 evaluation of IMC-TR1 in participants with advanced solid tumors and identifies safety and tolerability as central aims. It also specifies a primary endpoint: participants with a DLT from the first dose up to 6 weeks. The DLT definition is detailed and tied to the first treatment cycle, relatedness, dose dependence, and specified toxicity criteria.

The record also contains selected participant counts for serious and other adverse events across three dose groups. These data can be read descriptively as recorded counts for those groups. They do not provide a randomized estimate of a treatment effect, and the registry does not report uncertainty intervals or an adjusted comparison. The serious-event term percentages are also reported without term-specific counts in the information.

The study's stated aims included gathering evidence of antitumor activity, and a secondary outcome was response by RECIST version 1.1. That does not mean that a response result is available in the record. Neither the primary DLT count nor response findings are reported in the registry record. The record also does not report the maximum tolerated dose result, immunogenicity result, or pharmacokinetic results.

Accordingly, these registry entries do not establish the frequency of DLTs, the presence or absence of antitumor activity, or a comparative safety effect. They describe the questions asked, the design framework, and some adverse-event counts, while leaving important outcome results and analysis details unreported. General statistical principle: an endpoint definition describes how a result would be measured; it is not itself the result. Conclusions should be limited to the outcomes and analysis information actually recorded.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clinical question and the statistical evidence needed to answer it. The registry identifies DLTs during a defined early treatment period as the primary endpoint, but the endpoint count is not reported. A well-specified outcome is useful for interpretation, yet without its result it cannot quantify the study's primary safety finding.

The sequential design is also important. Dose escalation is a different setting from a randomized comparison, and the registry does not state allocation or describe a control group. The three adverse-event groups therefore provide descriptive information, not a direct estimate of what would have happened under a different dose in otherwise comparable participants. This distinction prevents dose-group contrasts from being overstated.

The record shows why denominators matter when reading event counts. The adverse-event summaries give both the number at risk and the number affected within each listed group. At the same time, small group counts are inherently limited in precision. General statistical principle: a sparse dataset can signal events worth characterizing but usually leaves substantial uncertainty about the underlying frequency and about differences between groups.

Finally, the registry lists multiple safety, response, and pharmacokinetic outcomes but no analyses. This makes transparent reporting of results and methods essential: outcome definitions alone do not indicate which analyses were performed, how missing data were handled, or whether multiple comparisons were considered. The record is statistically informative about design and endpoint definitions, while its gaps constrain what can be inferred from the posted results.

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 registry record does not report the observed count for the primary DLT endpoint. It therefore does not support a quantitative statement about how many participants met the primary endpoint or how that count varied by cohort. The primary endpoint is defined for participants who received at least one dose, but the size of that analysis population is not reported.

Only three dose groups appear in the adverse-event information. The record does not provide a complete participant flow by cohort, explain why participants received particular doses, or report cohort-specific baseline characteristics. The design is sequential, allocation is not stated, and there is no stated randomized comparator. These features limit interpretation of differences between the listed groups.

The arm description for Cohorts 10-12 is incomplete in the registry record. The available information begins to describe escalation from 800 mg to 1600 mg but does not provide the remainder of that description. It is not possible to fill in missing schedule or cohort details. The record also does not report dose-escalation decision rules or the criteria used to select the next dose.

Term-specific serious adverse-event counts, confidence intervals, and inferential comparisons are not reported in the registry information. Death counts are also not reported. The adverse-event summaries cannot be used to infer the full safety experience over all follow-up, and the primary DLT outcome is not interchangeable with all adverse events.

Although antitumor activity, maximum tolerated dose, immunogenicity, and pharmacokinetics are listed as outcomes, their results are not reported in the registry record. Statistical methods, handling of missing data, multiplicity procedures, and a sample-size justification are likewise not reported. These limitations leave the record useful for identifying design and outcome definitions, but restrict conclusions about results and precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of IMC-TR1 in Participants With Advanced Solid Tumors — NCT01646203.
• Registry record last updated 2019-01-18; status last verified 2018-08.
• Results first posted 2019-01-18.
• 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

NCT01646203 is a completed phase 1, sequential, unmasked study of IMC-TR1 in participants with advanced solid tumors. The registry records enrollment of 14, a start of 2012-07, and primary completion in 2014-10. The primary endpoint was the number of participants with DLTs from the first dose up to 6 weeks, among those who received at least one dose.

The registry lists three dose-group safety summaries and several secondary outcomes, including maximum tolerated dose, response, immunogenicity, and pharmacokinetics. It reports zero analyses. The primary DLT result and results for the listed secondary outcomes are not reported in the registry record. Allocation details, a statistical analysis plan, sample-size justification, missing-data methods, and multiplicity procedures are also not reported.

The adverse-event counts are descriptive and are not a randomized comparison. They do not establish a dose effect or provide a complete account of the study's safety or antitumor findings.