This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of INCB001158 Plus Epacadostat, With or Without Pembrolizumab, in Advanced Solid Tumors (NCT03361228), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a Treatment-emergent Adverse Event (TEAE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03361228 |
| Phase | Phase 1, Phase 2 |
| Condition | Solid Tumors |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Incyte Corporation |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced or metastatic solid tumors were eligible for the study as described in its brief summary. The registry record reports 5 enrolled participants. It does not report the number of participants by tumor type, disease characteristics, or other baseline features, so the population represented by the enrollment cannot be described in greater detail.
Intervention
The study evaluated INCB001158 in combination with epacadostat. The title and summary describe use with or without pembrolizumab. The posted adverse-event groups are labeled as INCB001158 50mg BID plus epacadostat plus pembrolizumab and INCB001158 75 mg BID plus epacadostat plus pembrolizumab. Detailed arm descriptions are not reported in the registry record.
Comparator
This was a nonrandomized study, not a randomized comparison against a control group. The registry lists two combination regimens, but they should not be treated as like-for-like comparator arms: allocation was not random, and the record does not provide a control-group description or an allocation method that would support a controlled treatment contrast. The study also included a tumor-expansion component in its official title.
Primary question
The phase 1 primary endpoint concerned safety and tolerability, measured as the number of participants with a treatment-emergent adverse event. A treatment-emergent adverse event was defined as an event first reported, or a pre-existing event that worsened, after the first dose of study treatment. No participants were analyzed for this endpoint. The record cites insufficient numbers and the risk of identifying a participant from reporting data on 1 person enrolled in cohort 2.
3. Trial Design
The official title describes an open-label, multicenter, nonrandomized, dose-escalation and tumor-expansion phase 1/2 study. Its stated purpose was to assess safety, tolerability, and antitumor activity of INCB001158 plus epacadostat, with or without pembrolizumab, in participants with advanced solid tumors. The registry lists a parallel model, no masking, and nonrandomized allocation. These features mean that participants and study staff were not masked to treatment, and treatment assignment was not randomized.
The registry lists INCB001158, epacadostat, and pembrolizumab as drug interventions. Two adverse-event groups are identified by dose and combination: INCB001158 50mg BID plus epacadostat plus pembrolizumab, and INCB001158 75 mg BID plus epacadostat plus pembrolizumab. The detailed descriptions for the listed arms are blank, so further regimen or cohort details are not reported in the registry record. The study title mentions dose escalation and tumor expansion, but the record does not give further operational details about those components.
The study enrolled 5 participants. Its status is terminated. The recorded start date is 2018-03-01, and the primary completion date is 2019-03-30. The reason for termination is not reported in the registry record. The primary endpoint is phase 1 only; the listed secondary outcomes include phase-specific safety and tolerability, objective response rate, disease control rate, duration of response, progression-free survival, and plasma pharmacokinetic profiles. The record lists 8 outcome measures, but reports 0 analyses. The primary safety endpoint was not analyzed, with the record citing insufficient numbers and a participant-identification risk.
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: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
Overall Study
| Stage | INCB001158 50mg BID+ Epacadostat + Pembrolizumab | INCB001158 75 mg BID + Epacadostat + Pembrolizumab |
|---|---|---|
| STARTED | 4 | 1 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 4 | 1 |
Reasons for not completing this period:
| Reason | INCB001158 50mg BID+ Epacadostat + Pembrolizumab | INCB001158 75 mg BID + Epacadostat + Pembrolizumab |
|---|---|---|
| Other | 1 | 1 |
| Death | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
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: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
| Characteristic | Unit | INCB001158 50mg BID+ Epacadostat + Pembrolizumab | INCB001158 75 mg BID + Epacadostat + Pembrolizumab | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | |
| Sex: Female, Male: Female | participants | — | — | — |
| Sex: Female, Male: Male | participants | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as Phase 1 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a Treatment-emergent Adverse Event (TEAE), measured over Up to approximately 12 months per subject.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The phase 1 primary endpoint was the number of participants with a treatment-emergent adverse event, or TEAE, during a timeframe of up to approximately 12 months per subject. The registry defines a TEAE as an adverse event reported for the first time after the first dose of study treatment, or a pre-existing event that worsened after that dose. The endpoint therefore concerns the occurrence of events after treatment begins, rather than only events judged to have been caused by treatment. The registry definition does not say that an event had to be attributed to study treatment to count as treatment-emergent.
General statistical context: In early-phase studies, counting participants with adverse events is a descriptive way to characterize safety and tolerability in the observed study groups. It can show how many participants experienced events under the recorded endpoint definition, but a count alone does not establish causation or compare risk reliably across groups. A participant-level summary also differs from a count of event episodes: one participant may experience more than one event, and the endpoint as worded focuses on the number of participants affected.
The endpoint was not analyzed in this study. The registry record attributes this to insufficient numbers and to the risk of identifying a participant through reporting data on 1 person enrolled in cohort 2. Consequently, no primary endpoint estimate or uncertainty interval is reported in the record. The adverse-event group figures are separate descriptive information and do not replace an analysis of the stated primary endpoint across the study population.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main interpretive constraint is that the stated phase 1 primary safety endpoint has no analysis. The registry record reports 5 enrolled participants but says no patients were analyzed for the primary endpoint, citing insufficient numbers and the risk of identifying a participant from reporting data on 1 person enrolled in cohort 2. Thus the registry does not provide a study-wide estimate of the number of participants with a TEAE, nor an uncertainty interval for that estimate. The absence of an analysis is not evidence that no adverse events occurred.
The posted adverse-event information is limited to two groups labeled as INCB001158, epacadostat, and pembrolizumab combinations. In the 50mg BID group, 4 participants were listed as at risk for serious adverse events and 3 as affected; 4 were listed as at risk for other adverse events and 4 as affected; deaths were recorded for 3 participants. In the 75 mg BID group, 1 participant was listed as at risk for serious adverse events and 1 as affected; 1 was listed as at risk for other adverse events and 0 as affected; deaths were recorded for 0 participants. These are descriptive counts in very small groups, not estimates from a randomized comparison.
The registry also lists serious-event terms with percentages: Ataxia and Brain oedema at 100.0% each, and Myocardial infarction, Clostridium difficile infection, Arthralgia, and Hydronephrosis at 25.0% each. The denominators and event-specific participant counts underlying these percentages are not reported in the registry record. The percentages therefore should not be used to infer counts or compare event rates between treatment groups.
Because allocation was nonrandomized, the listed groups are not like-for-like controls. Differences in counts between them cannot be interpreted as treatment effects. The record does not report attribution of the deaths or adverse events to study treatment, and does not provide enough detail to infer causation. It also reports no outcome analyses. The data support only a narrow description of the recorded safety counts and terms; they do not establish the incidence of events in a broader population or answer the study’s antitumor-activity questions.
9. Statistical Methods Explained
What the design can establish
The study is described as open-label, multicenter, nonrandomized, and parallel, with dose-escalation and tumor-expansion components. In a randomized study, chance allocation is used to form groups with the aim of limiting systematic differences between them. Here, allocation was explicitly nonrandomized. As a result, the treatment groups cannot be assumed to have comparable participant characteristics, and a contrast between their observed outcomes would not by itself isolate a treatment effect. The record does not report the assignment procedure or enough cohort detail to assess how participants entered each group.
Open-label means the study was not masked. General statistical context: knowledge of treatment can affect subjective reporting or assessment, although the record does not describe whether this occurred. The multicenter description indicates that the study involved more than one center, but the number or identities of centers are not reported in the registry record. The official title identifies both dose escalation and tumor expansion; additional procedures for either component are not reported.
How to interpret the primary endpoint
The primary endpoint counts participants with a TEAE. The event definition is based on timing: an event first reported after first dose, or worsening of a pre-existing event after first dose. This definition distinguishes treatment-emergent events from events that did not newly occur or worsen after treatment began, but it does not establish that treatment caused an event. General statistical context: participant counts are useful for a concise safety description, while event counts can be larger if a participant experiences multiple events. The stated endpoint is participant-based.
No primary endpoint analysis was conducted according to the registry record. It cites insufficient numbers and a risk of identifying a participant by reporting data on 1 person enrolled in cohort 2. Since no primary endpoint estimate is reported, there is no confidence interval to interpret. General statistical context: a confidence interval describes the range of estimates compatible with the data and the method used, under its assumptions. It does not remedy a lack of analyzed data or convert a small, selected group into a representative sample.
Why the adverse-event groups are descriptive
The posted adverse-event figures give participants at risk, participants affected, and deaths for two dose-labeled combination groups. These figures can be read as counts for the groups as listed. They do not provide a randomized comparison, and the group sizes are small. General statistical context: with few participants, each individual outcome can have a substantial influence on a group summary, and estimates are usually imprecise. The registry record does not report an uncertainty interval for these counts or percentages.
Serious adverse events and other adverse events are reported as separate categories. The record does not define in this summary whether a participant could be represented in both categories, so the categories should not be treated as mutually exclusive. It also does not give event-level timelines, severity grading details, treatment attribution, or a narrative explaining the deaths. The listed serious-event percentages should be read as posted descriptive percentages; the denominator for each term is not reported in the registry record.
What a planning illustration means
General statistical context: sample-size calculations for planning ask how many participants or events a hypothetical design would require under stated assumptions. The planning illustration associated with this study is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses total events, while other outcomes use participants per arm.
Those assumptions describe a planning exercise, not the trial’s own design or an observed power calculation. In particular, the registry describes the study as nonrandomized, whereas the illustration assumes equal allocation between two arms. The registry record does not report a protocol-based sample-size justification. The underlying effect estimates and specific planning counts are not reported in the registry record. Planning calculations cannot compensate for the lack of a primary endpoint analysis, and they do not show that the trial had a particular probability of detecting an effect.
What is absent from the analysis record
The record lists 8 outcome measures and 0 analyses. It does not report analysis methods for the listed secondary outcomes, a statistical analysis plan, a missing-data method, interim analyses, or definitions of analysis populations. General statistical context: the exact method matters because outcome definitions, censoring, missing observations, and choices among multiple endpoints can affect interpretation. Without those details and reported outcome analyses, the registry does not support reconstruction of efficacy estimates or formal treatment comparisons.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes: the phase 1 primary safety and tolerability endpoint; phase-specific safety information; objective response rate; disease control rate; duration of response; progression-free survival; and plasma pharmacokinetic profiles. The record lists 8 outcome measures and 0 analyses. It does not report a multiplicity strategy, such as a prespecified ordering of hypotheses or an adjustment to account for testing several outcomes. It also does not report whether formal hypothesis tests were planned for the secondary outcomes.
General statistical context: When many outcomes or hypotheses are examined, the chance of obtaining at least one apparently noteworthy finding can increase if results are interpreted without accounting for that multiplicity. A prespecified analysis plan helps clarify which outcomes are primary, which are supportive, and how the interpretation should handle multiple comparisons. Since no outcome analyses are reported, the registry record does not allow assessment of whether multiplicity affected any findings.
Missing-data methods and analysis-population definitions are not reported in the registry record. The record does not describe how incomplete observations, withdrawals, or participants who did not contribute particular endpoint data would be handled. It also does not specify whether any analysis population would include all enrolled participants or a subset. These omissions limit interpretation of any outcome summaries that might otherwise be available. The primary endpoint itself was not analyzed because of the stated concern about insufficient numbers and participant identification. Interim analyses and the statistical analysis plan are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| INCB001158 50mg BID+ Epacadostat + Pembrolizumab | 3 | 4 | 75.0% |
| INCB001158 75 mg BID + Epacadostat + Pembrolizumab | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| INCB001158 50mg BID+ Epacadostat + Pembrolizumab | 3 of 4 |
| INCB001158 75 mg BID + Epacadostat + Pembrolizumab | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| INCB001158 50mg BID+ Epacadostat + Pembrolizumab | 4 of 4 |
| INCB001158 75 mg BID + Epacadostat + Pembrolizumab | 0 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | INCB001158 50mg BID+ Epacadostat + Pembrolizumab | INCB001158 75 mg BID + Epacadostat + Pembrolizumab |
|---|---|---|---|
| Myocardial infarction | Cardiac disorders | 1 of 4 | 0 of 1 |
| Clostridium difficile infection | Infections and infestations | 1 of 4 | 0 of 1 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 4 | 0 of 1 |
| Ataxia | Nervous system disorders | 0 of 4 | 1 of 1 |
| Brain oedema | Nervous system disorders | 0 of 4 | 1 of 1 |
| Hydronephrosis | Renal and urinary disorders | 1 of 4 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | INCB001158 50mg BID+ Epacadostat + Pembrolizumab | INCB001158 75 mg BID + Epacadostat + Pembrolizumab |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 2 of 4 | 0 of 1 |
| Fatigue | General disorders | 2 of 4 | 0 of 1 |
| Pyrexia | General disorders | 2 of 4 | 0 of 1 |
| Dry eye | Eye disorders | 1 of 4 | 0 of 1 |
| Abdominal pain lower | Gastrointestinal disorders | 1 of 4 | 0 of 1 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 4 | 0 of 1 |
| Constipation | Gastrointestinal disorders | 1 of 4 | 0 of 1 |
| Dry mouth | Gastrointestinal disorders | 1 of 4 | 0 of 1 |
| Nausea | Gastrointestinal disorders | 1 of 4 | 0 of 1 |
| Vomiting | Gastrointestinal disorders | 1 of 4 | 0 of 1 |
Serious events with the highest arm-level rate: ataxia (100.0%), brain oedema (100.0%), myocardial infarction (25.0%), clostridium difficile infection (25.0%), arthralgia (25.0%).
The serious-adverse-event figures are participant counts for the two listed combination groups, not randomized treatment comparisons. For INCB001158 50mg BID plus epacadostat plus pembrolizumab, 4 participants were at risk for serious adverse events and 3 were affected; 4 were at risk for other adverse events and 4 were affected; 3 deaths were recorded. For INCB001158 75 mg BID plus epacadostat plus pembrolizumab, 1 participant was at risk for serious adverse events and 1 was affected; 1 was at risk for other adverse events and 0 were affected; 0 deaths were recorded.
The record lists Ataxia and Brain oedema at 100.0% among the top serious-event terms, and Myocardial infarction, Clostridium difficile infection, Arthralgia, and Hydronephrosis at 25.0%. The term-specific denominators are not reported in the registry record. These percentages should not be converted into participant counts, and the available information does not show whether an individual could contribute more than one event term.
General statistical context: counts from small groups are highly sensitive to the experience of individual participants. The figures do not establish that a study drug caused an event or death. Attribution, timing, and further clinical detail are not reported in the registry record. The study-wide primary TEAE endpoint was not analyzed, so these group summaries should not be treated as a substitute for that endpoint.
12. What the Result Does, and Does Not, Mean
The registry record describes a small, nonrandomized phase 1/2 study of INCB001158 plus epacadostat, with or without pembrolizumab, in advanced solid tumors. The study enrolled 5 participants and is listed as terminated. Its primary phase 1 endpoint was a participant count for treatment-emergent adverse events, but no patients were analyzed for that endpoint. The record cites insufficient numbers and a risk of identifying a participant from reporting data on 1 person enrolled in cohort 2. Accordingly, there is no primary endpoint estimate to interpret.
The posted safety information gives counts for two dose-labeled groups that both include epacadostat and pembrolizumab. Those figures describe the participants recorded as at risk and affected, along with deaths. They do not establish that the interventions caused the events, and they do not provide a basis for comparing the regimens as if participants had been randomly allocated. The registry does not report event attribution, detailed outcome analyses, or uncertainty intervals for these summaries.
The study’s stated aim included antitumor activity, and its listed outcomes include response and time-to-event measures. However, the registry lists 0 analyses. The record therefore does not provide reported results for those outcomes that can be used to characterize antitumor activity. The absence of reported analyses should not be interpreted as evidence of either benefit or lack of benefit.
General statistical context: estimates from small groups are uncertain, and a nonrandomized design is vulnerable to differences between participants in the groups being described. Even a numerical difference between group summaries would not, on its own, show that treatment caused the difference. The registry information supports a limited account of the design and posted safety counts, but not a conclusion about treatment efficacy, comparative safety, or outcomes in a wider population.
13. Why This Trial Matters Statistically
This record illustrates why the distinction between a study’s stated objectives and its analyzable results matters. The study was designed as a phase 1/2 evaluation of safety, tolerability, and antitumor activity, but the registry reports no analyses and says the primary endpoint was not analyzed. A protocol-level question can therefore remain unanswered in the posted results, even when the study includes a defined endpoint and adverse-event group summaries.
It also shows the limits of reading counts from small, nonrandomized groups as comparisons. The two posted adverse-event groups differ in the number at risk, and allocation was not randomized. General statistical context: randomization helps support causal comparisons by balancing measured and unmeasured factors on average; without it, group differences may reflect participant or cohort differences as well as treatment. Small groups further restrict how precisely event frequencies can be characterized.
The record is also useful for distinguishing a treatment-emergent event from a treatment-caused event. The primary endpoint definition concerns when an event occurred or worsened relative to the first dose. It does not, by itself, establish causal attribution. Similarly, recorded deaths and serious-event terms are safety observations, not proof that treatment caused those outcomes.
Finally, the record notes a privacy-related reason for not analyzing the primary endpoint: risk of identifying a participant in cohort 2. This makes transparent reporting constraints part of the statistical interpretation. The available information supports careful description, while leaving important questions about the planned analyses, outcome results, and handling of missing data unanswered.
14. 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 most important trial-specific limitation is the absence of a primary endpoint analysis. The registry states that no patients were analyzed because of insufficient numbers and the risk of identifying a participant from reporting data on 1 person enrolled in cohort 2. The total enrollment was 5, so the record offers little basis for precise characterization of outcomes. It does not provide a primary endpoint estimate or an uncertainty interval.
The design was nonrandomized and open-label. The listed adverse-event groups should therefore not be interpreted as randomized controls, and the record does not describe enough about participant assignment or cohort characteristics to assess comparability. Although the official title names dose escalation and tumor expansion, detailed procedures and arm descriptions are not reported in the registry record.
The posted adverse-event summaries cover two triple-combination groups. A comparable safety summary for the INCB001158 plus epacadostat regimen without pembrolizumab is not reported in the registry record. The record does not provide term-specific denominators, event attribution, detailed event timing, or explanations for the deaths. It also does not report analyses of the listed response, disease-control, duration-of-response, progression-free-survival, or pharmacokinetic outcomes.
Analysis-population definitions, missing-data methods, interim analyses, multiplicity handling, and the statistical analysis plan are not reported in the registry record. The reason for study termination is also not reported. These limits prevent a fuller assessment of the study’s conduct and outcome interpretation beyond the design description and posted descriptive safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of INCB001158 Plus Epacadostat, With or Without Pembrolizumab, in Advanced Solid Tumors — NCT03361228.
- Registry record last updated 2020-05-21; status last verified 2020-05.
- Results first posted 2020-05-21.
- 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.
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18. Record Summary
NCT03361228 is an open-label, multicenter, nonrandomized phase 1/2 study described as dose escalation and tumor expansion. It evaluated INCB001158 plus epacadostat, with or without pembrolizumab, in advanced solid tumors. The registry reports 5 enrolled participants, a start date of 2018-03-01, a primary completion date of 2019-03-30, and terminated status.
The phase 1 primary endpoint was the number of participants with a TEAE over up to approximately 12 months per subject. No patients were analyzed for this endpoint; the record cites insufficient numbers and a risk of identifying a participant from reporting data on 1 person enrolled in cohort 2. The posted adverse-event information describes two triple-combination groups, but does not form a randomized comparison. The registry lists 8 outcome measures and 0 analyses. The reason for termination, analysis methods, and results for the listed antitumor-activity outcomes are not reported in the registry record.