A Safety and Efficacy Study of CC-90011 in Participants With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Efficacy Study of CC-90011 in Participants With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas (NCT02875223), a non-randomized phase 1 study. The primary outcome is Part A - Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

The clinical question is primarily about early safety and dose finding, rather than a comparative estimate of efficacy. The primary outcome is a participant count, and the registry describes rules for deciding which toxicities qualify as dose limiting. The registry record does not report the count of participants with dose-limiting toxicities, the maximum tolerated dose, or the recommended Phase 2 dose. It therefore does not provide the posted primary result needed to answer the dose-finding question.

Preliminary efficacy was also part of the study’s stated purpose. The listed secondary outcomes include response, clinical benefit, duration of response, progression-free survival, and overall survival, as well as pharmacokinetic measures. However, outcome analyses are not reported in the registry record. The study description alone cannot establish how participants fared on these outcomes.

3. Trial Design

This was a Phase 1, open-label, nonrandomized, parallel study of CC-90011. The registry describes it as a first-in-human dose-escalation and expansion study in participants with relapsed and/or refractory solid tumors and non-Hodgkin lymphomas. Enrollment was 75. The study started on 2016-08-31, its primary completion date is recorded as 2024-03-25, and its status is terminated. The reason for termination is not reported in the registry record.

The study had two parts. Part A explored escalating oral doses, with the stated aim of estimating the maximum tolerated dose. Part B evaluated CC-90011 at or below the maximum tolerated dose in selected expansion cohorts, with the stated aim of further defining the recommended Phase 2 dose. The description says the selected cohorts were intended to include approximately 10-20 evaluable participants each. That planned cohort size is not a statement of observed enrollment in each cohort.

The patient groups were clinically and diagnostically varied. The solid-tumor population was enriched for specified neuroendocrine tumor types, while the lymphoma population included marginal zone lymphoma and its specified subtypes and transformation. Results pooled across such groups, if available, would need to be interpreted in light of those differences; subgroup outcome estimates are not reported in the registry record.

Because allocation was nonrandomized and masking was absent, the study was not designed as a blinded, randomized treatment comparison. Dose escalation and expansion serve different purposes: escalation explores tolerability across dose levels, while expansion collects further observations at selected doses and in selected groups. Differences between dose groups cannot by themselves establish that dose caused differences in outcomes. Participants may differ across cohorts, and cohort sizes are not equal. The registry record does not report further details of the allocation procedure, the dose-escalation algorithm, or the statistical analysis plan.

CC-90011, rifampicin, and itraconazole are listed as interventions, but the arm descriptions are blank. The registry record therefore does not explain the specific study procedures or comparisons involving rifampicin or itraconazole. It also does not report a separate control arm.

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 were not enrolled in Part C and Part D as the study was terminated early.

Only the first 6 of 13 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT Evaluable Population includes participants in Part A are evaluable for DLT if they received at least 75% of the total planned dose of CC-90011 during Cycle 1.

5. Baseline Characteristics

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

Only the first 6 of 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part A - Number of Participants With Dose Limiting Toxicities (DLTs), measured over Cycle 1 (Each cycle is of 28 days).

The primary endpoint is the number of participants with dose-limiting toxicities in Part A during Cycle 1, a 28-day period. The registry defines a dose-limiting toxicity using specified safety criteria, including certain severe non-hematologic and hematologic toxicities, adverse events requiring dose reduction during Cycle 1, and other toxicities judged dose limiting by the safety committee. Some Grade 3 events are excepted under specified circumstances. The endpoint is therefore a protocol-defined safety count, not a count of every adverse event.

The endpoint is used in dose finding because early toxicity observations can help identify dose levels that warrant further evaluation. The registry definition says the maximum tolerated dose is the highest dose at which less than 33% of the treated population has a dose-limiting toxicity in the first cycle, with at least 6 evaluable participants treated at that dose. This is the protocol’s stated decision rule, not a result. The actual dose-limiting-toxicity count by dose and the selected maximum tolerated dose are not reported in the registry record.

The primary analysis population is described as the DLT Evaluable Population. Participants in Part A were evaluable for dose-limiting toxicity if they received at least 75% of the total planned CC-90011 dose during Cycle 1. This exposure requirement matters when interpreting a count: it identifies who is included in the endpoint population and does not establish the number enrolled, treated, or evaluable at each dose. Those dose-specific numbers are not reported in the registry record.

A count is useful for describing how many participants met the safety definition, but a count alone does not convey the precision of an estimated event probability. The registry record does not report a confidence interval or an analysis of the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a dose-escalation study estimate?

In a dose-escalation study, participants are assigned to dose levels according to a study procedure, and early safety observations help inform which dose levels receive further evaluation. The aim is not the same as estimating a treatment effect against a concurrent randomized control. Here, the stated aim for Part A was to explore escalating oral doses and estimate the maximum tolerated dose. The stated aim for Part B was to evaluate CC-90011 at or below that dose in selected expansion cohorts and further define the recommended Phase 2 dose. The actual escalation decisions and selected doses are not reported in the registry record.

The protocol definition makes the primary endpoint a participant-level safety outcome within a specified assessment window. It sets out event types and exceptions, and includes events requiring a dose reduction or judged dose limiting by the safety committee. Defining the endpoint in advance is important because it limits ambiguity about which toxicities count. The reported primary endpoint, however, is a number of participants, not a list of individual events or a risk estimate. Its interpretation depends on knowing both the count and the corresponding evaluable population at each dose, which are not reported in the registry record.

Why does the evaluable population matter?

The registry’s DLT Evaluable Population requires participants in Part A to receive at least 75% of the planned CC-90011 dose during Cycle 1. An exposure rule can help define whether there was sufficient opportunity to observe the endpoint, but it also means the analysis population may not be identical to all enrolled participants. The record does not give the dose-specific numbers enrolled, treated, excluded, or evaluable, or reasons participants may not have met the exposure rule. Without those details, it is not possible to assess how exclusions affected the endpoint count.

More generally, missing observations can affect estimates when participants with unavailable outcomes differ from those with observed outcomes. A complete analysis would describe the extent and reasons for missingness and how it was handled. Those details are not reported in the registry record. No assumption about missing outcomes should be read into the endpoint definition.

What can counts and uncertainty tell us?

For a binary event such as whether a participant experienced a dose-limiting toxicity, a count records the number meeting the definition. A corresponding proportion would also require the relevant denominator. The record defines the endpoint as a participant count and does not post the primary count or its dose-specific denominators. A confidence interval, in general, conveys uncertainty around an estimate; it does not remedy missing outcome information or eliminate design limitations. No primary endpoint confidence interval is reported in the registry record.

The adverse-event listings also use counts of affected participants and numbers at risk. They are descriptive safety summaries, not adjusted comparisons. When group sizes differ, raw counts should not be compared as if they represented the same amount of information. Even proportions would require cautious interpretation: the study was nonrandomized, and the registry record does not report a statistical comparison across dose groups.

Over-dispersion is a general issue when count data vary more than a simple model expects. In that situation, a model that assumes less variation can produce uncertainty estimates that are too narrow. This is a general statistical consideration, not a reported feature or analysis of this study. The primary endpoint is described as a count of participants with an event, and the registry record does not report a model or dispersion estimate.

How should sample-size calculations be understood?

A planning illustration based on an observed effect is distinct from the trial’s original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events based on the Schoenfeld approach; other outcomes are expressed as participants per arm. These assumptions describe a hypothetical planning exercise, not the nonrandomized dose-escalation design itself. No sample-size justification from the study protocol is reported in the registry record.

Such calculated sample sizes are planning illustrations, not observed power. Observed power is not a substitute for interpreting an estimate and its uncertainty after data collection. The registry record does not provide the analysis estimates needed to interpret a planning calculation in relation to an observed treatment effect. In addition, equal allocation between two arms does not describe the allocation structure of the listed dose groups.

What does multiplicity mean in this study?

Multiplicity arises when many outcomes, groups, or statistical tests are considered. Repeated testing can increase the chance of finding an apparently notable result by chance, so a statistical plan may define a primary outcome, testing order, or adjustment procedure. The registry lists 18 outcome measures, including safety, response, survival, and pharmacokinetic outcomes, but outcome analyses and any multiplicity procedure are not reported in the registry record. It is therefore not possible to determine whether or how multiplicity was addressed.

The registry lists no analyses. That absence means there are no posted test statistics or estimates to assess for model choice, covariate adjustment, confidence-interval construction, or sensitivity analysis. The statistical analysis plan, including any interim analyses and detailed analysis methods, is not reported in the registry record. No such methods should be inferred from the Phase 1 label or from the endpoint definitions.

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("Part A 1.25 mg", "Part A 2.5 mg", "Part A 5 mg", "Part A 10 mg", "Part A 20 mg", "Part A 40 mg")
n      <- c(4, 4, 5, 4, 5, 6)
events <- c(0, 0, 0, 0, 0, 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  Part A 1.25 mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Part A 2.5 mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Part A 5 mg  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Part A 10 mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Part A 20 mg  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Part A 40 mg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures spanning dose-limiting toxicities, other safety outcomes, response, duration of response, progression-free and overall survival, and pharmacokinetic measures. Considering multiple outcomes can create multiplicity: repeated statistical testing can make chance findings more likely. A prespecified testing hierarchy or adjustment method can address that concern, but no multiplicity method is reported in the registry record. The outcome list alone does not show which outcomes were analyzed or how results were interpreted.

The registry record reports no analyses. It does not report an analysis plan, interim analyses, statistical models, covariate adjustments, or sensitivity analyses. It therefore does not establish whether any such procedures were used. The record also does not report a reason for termination or explain whether termination affected planned analyses.

The primary endpoint population is defined by an exposure criterion: Part A participants had to receive at least 75% of the planned CC-90011 dose during Cycle 1 to be DLT evaluable. The record does not report how many participants met this criterion at each dose, how many did not, or the reasons for any missing endpoint information. It also does not describe imputation or another approach to missing data. Since evaluability is not necessarily identical to enrollment, the overall enrollment of 75 should not be assumed to be the denominator for the primary endpoint.

These omissions limit assessment of whether the reported safety counts and any eventual analyses represent all treated participants, a defined evaluable population, or another analysis set. They also prevent evaluation of how missing outcomes or multiple analyses may have influenced conclusions. The analysis populations beyond the stated DLT Evaluable Population are not reported in the registry record.

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 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 (50.0%), neutropenia (25.0%), small intestinal obstruction (25.0%), hyperglycaemia (25.0%), hypokalaemia (25.0%).

The registry reports serious adverse events, other adverse events, and deaths separately for Part A dose groups and the Part B 60 mg group. “At risk” is the number of participants represented for the relevant category, while “affected” is the number reported with an event in that category. For example, in Part A 1.25 mg, 2 participants were reported with serious adverse events among 4 at risk; in Part B 60 mg, 7 were reported among 25 at risk. These are descriptive counts, not randomized comparisons.

The listing also reports deaths by group, but does not establish that a death was caused by CC-90011 or by an adverse event. The timing, causes, and relationship to treatment are not reported in the registry record. Serious-event counts should not be equated with dose-limiting-toxicity counts: the primary endpoint has its own definition and assessment period, and the registry does not identify which reported adverse events met it.

The registry lists thrombocytopenia at 50.0% among the top serious-event terms, and neutropenia, small intestinal obstruction, hyperglycaemia, hypokalaemia, and pleural effusion at 25.0% each. The record does not provide enough detail to infer how these terms were distributed across dose groups or whether they were treatment-related. Unequal group sizes, nonrandom allocation, and the absence of event-level context limit comparisons.

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

The record describes a first-in-human Phase 1 study designed to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of CC-90011 in participants with relapsed and/or refractory solid tumors and non-Hodgkin lymphomas. Its dose-escalation and expansion structure addresses early dose-finding questions. The DLT definition and the stated maximum-tolerated-dose rule explain how safety observations were intended to inform dose selection.

What the registry record does not show is equally important. It does not report the primary count of participants with dose-limiting toxicities, the dose-specific evaluable denominators, or the selected maximum tolerated dose. It also does not report analyses for the listed response, survival, or pharmacokinetic outcomes. Thus, the listed aims and outcomes cannot be treated as evidence of a particular result.

The serious and other adverse-event counts are descriptive observations across nonrandomized groups. They do not establish that CC-90011 caused an event, and the deaths listed do not establish cause or treatment relationship. Nor can adverse-event counts substitute for the protocol-defined DLT endpoint. The record does not provide sufficient detail to connect individual events to the primary endpoint or to compare safety causally between dose groups.

This information also does not establish how CC-90011 compares with another treatment, because the study was not randomized and a control comparison is not reported. It cannot establish a treatment effect or a reliable estimate of efficacy from outcomes for which analyses are absent. The study’s terminated status does not, by itself, explain why it ended or indicate what its findings were.

In general, early-phase studies can characterize observed safety and guide further study, but their conclusions depend on the results and analysis details. Here, the registry describes the intended framework, while the outcome analyses necessary to evaluate its principal questions are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a trial’s stated objective and an interpretable posted result. The record defines a clinically relevant dose-limiting-toxicity endpoint, specifies the Cycle 1 assessment period, and describes an evaluability rule. It also states how the maximum tolerated dose was to be selected. Those details make the intended decision framework understandable, but they cannot replace the missing endpoint counts and denominators.

The study also shows why design context matters when reading safety summaries. The dose groups were nonrandomized, differed in size, and included separate escalation and expansion parts. Counts across those groups do not have the balance or comparability created by random assignment. Without outcome analyses and fuller population information, readers cannot determine whether numerical differences reflect dose, participant mix, exposure, or other factors.

A further statistical lesson is that the collection of many outcome measures does not itself constitute evidence for each outcome. The registry lists safety, response, survival, and pharmacokinetic measures, but reports no analyses. Multiplicity procedures, missing-data handling, and detailed analysis methods are not described. Those omissions limit both reproducibility and assessment of uncertainty.

Finally, the record distinguishes an endpoint count from an adverse-event summary. A protocol-defined DLT endpoint has a particular definition and window; broader serious and other adverse-event counts answer different descriptive questions. Keeping those measures separate prevents safety listings from being mistaken for the primary dose-finding result. In this study, the available reporting supports a description of design and selected safety counts, but not a statistical conclusion about the primary endpoint or efficacy.

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 primary endpoint result, dose-specific DLT counts, or evaluable denominators. It therefore does not permit assessment of the primary safety question or verification of the stated maximum-tolerated-dose rule. The recommended Phase 2 dose is also not reported.

The study population included varied solid tumors and lymphoma subtypes, but subgroup-specific outcome analyses are not reported. The overall enrollment of 75 does not show how participants were distributed across doses, cohorts, or analysis populations. The record does not give the number who received treatment, completed Cycle 1, or met the DLT evaluability criterion at each dose.

Nonrandomized allocation and open-label conduct limit causal interpretation of differences among dose groups. The record does not provide a control group for comparison, and the arm descriptions do not clarify how rifampicin and itraconazole were used. It also does not report the reason for termination, the detailed analysis plan, missing-data handling, or multiplicity methods.

Safety reporting is limited by the absence of event-level timing, treatment relationship, and details linking adverse events to the DLT definition. The reported deaths do not include causes or attribution in the registry information. Confidence intervals and outcome analyses are not reported, limiting assessment of statistical precision. These limitations concern what the registry record reports; they do not establish that the information was never collected.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety and Efficacy Study of CC-90011 in Participants With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas — NCT02875223.
• Registry record last updated 2025-04-20; status last verified 2025-04.
• Results first posted 2025-04-20.
• 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

NCT02875223 is a Phase 1, open-label, nonrandomized study of CC-90011 in participants with relapsed and/or refractory solid tumors and non-Hodgkin lymphomas. The study used dose escalation and expansion, with stated aims of estimating the maximum tolerated dose and further defining the recommended Phase 2 dose. Enrollment was 75. The recorded status is terminated; the reason is not reported in the registry record.

The primary endpoint was the number of participants with dose-limiting toxicities in Part A during Cycle 1, defined as 28 days. The registry provides the endpoint definition and the DLT-evaluable population criterion, but does not report the primary result, selected dose, or outcome analyses. It lists serious and other adverse-event counts and deaths by group, along with selected serious-event terms. These are descriptive safety data and do not establish causality or a treatment comparison.