A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203) (NCT02318277), a na phase 1, phase 2 study. The primary outcome is Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE).

2. Clinical Question

The registry record describes a study exploring the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of INCB024360, also called epacadostat, given with MEDI4736, also called durvalumab. The study concerned selected advanced solid tumors, with listed conditions including solid tumors, head and neck cancer, lung cancer, and urothelial cancer. Its primary Phase 1 endpoint was the number of participants with treatment-emergent adverse events.

In Phase 1, the study used dose cohorts for the combination. The arm description says durvalumab was given at selected dose levels every 2 weeks, with epacadostat starting at 25 mg BID and then undergoing dose escalations until MTD or PAD was identified. Phase 2 included cohorts receiving epacadostat 100 mg or 300 mg with durvalumab 10 mg/kg. The registry lists adverse-event outcomes, and it also identifies response, durability of response, progression-free survival, pharmacokinetics, and immunogenicity among its secondary outcomes.

The record does not describe a randomized comparison. It identifies the study model as single group and allocation as NA. Therefore, the central statistical question is descriptive: what adverse events were recorded in the listed cohorts, and how should those counts be understood in light of the study’s design? The posted data do not support a like-for-like comparison of the combination against a control treatment. Nor do the adverse-event counts alone establish whether an event was caused by study treatment.

3. Trial Design

ECHO-203 is registered as a Phase 1/2 study and is marked completed. The registry lists enrollment of 176. The study started on 2015-01-05, and primary completion is recorded as 2019-08-28. These dates and enrollment describe the study record; they do not by themselves indicate how many participants contributed to any particular endpoint or cohort.

The design is listed as single group, with allocation NA and masking none. Accordingly, the combination cohorts are not randomized treatment arms intended to provide a like-for-like control comparison. Phase 1 included several epacadostat dose levels paired with durvalumab, while Phase 2 included the epacadostat 100 mg and 300 mg cohorts with durvalumab 10 mg/kg. The registry describes the Phase 1 approach as dose escalation, with durvalumab at selected dose levels every 2 weeks and epacadostat beginning at 25 mg BID, followed by escalation until MTD or PAD was identified. Whether MTD or PAD was identified, and what values were selected, is not reported in the registry record.

The primary endpoint is a Phase 1 safety outcome. The record defines treatment-emergent adverse events as events reported for the first time or worsening of a pre-existing event after the first dose of study treatment. The timeframe is the duration of study treatment and up to 90 days after the last dose, described as approximately 3 years. Phase 2 includes treatment-emergent adverse events as a secondary outcome. Other listed secondary outcomes cover response, duration of response, progression-free survival, pharmacokinetics, and immunogenicity.

Sample-size justification, the protocol’s detailed statistical plan, and the reason for the specific cohort sizes are not reported in the registry record. The posted counts should therefore be read as descriptions of the observed cohorts rather than as results from a randomized efficacy comparison.

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: A total of 235 participants were screened and 59 participants were screen failures. A total of 176 participants ( 34 participants in Phase 1 and 142 in Phase 2) were enrolled in the study. Study enrollment was permanently discontinued on 24 Apr 2018 as a strategic decision. At the time of data cut-off, 28 Aug 2019, 1 participant was ongoing.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Phase 1 safety population includes all subjects enrolled in the Phase 1 portion of the study who received at least 1 dose of INCB024360 or MEDI4736. Treatment groups were determined according to the actual treatment the subject received on Day 1 regardless of the actual study drug the subject received during participation in the study.

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: Intent-to-Treat Population who are enrolled in Phase 1 and 2 part of the study

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE), measured over Duration of study treatment and up to 90 days after the last dose [approximately 3 years].

The primary endpoint is the Phase 1 number of participants with treatment-emergent adverse events. The registry defines such an event as an adverse event reported for the first time, or a worsening of a pre-existing event, after the first dose of study treatment. The stated observation period runs for the duration of study treatment and up to 90 days after the last dose, approximately 3 years.

This endpoint is used to describe safety during exposure to the combination. Counting participants with events can show how many people in a cohort experienced an event under the endpoint definition. It is distinct from counting every event occurrence: a participant may have more than one event, while a participant count records whether people experienced an event. The registry identifies the unit as participants and the measure as a count of participants.

The primary endpoint title does not itself describe severity, seriousness, causality, or event type. Those are separate characteristics. In particular, a treatment-emergent event is defined by its timing relative to treatment, not by proof that treatment caused it. The registry’s adverse-event summaries separately report serious adverse events and other adverse events for the listed cohorts.

Results for the complete primary endpoint are not reported in the registry record as a single overall estimate with an uncertainty interval. The cohort-level safety counts can be read descriptively, but they should not be treated as a comparative treatment effect or as a complete account of the safety profile.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a safety endpoint recorded as a count of participants, the basic interpretation is descriptive. The count says how many participants in the stated population met the event definition during the stated observation period. It does not automatically say how many separate event episodes occurred, how long participants were exposed, or whether the events were caused by treatment. In this record, the primary endpoint definition is based on events first reported or worsening after the first dose.

What a cohort count can tell the reader

A cohort-specific count is meaningful only alongside its cohort and denominator. The registry’s adverse-event summaries list participants at risk and affected for serious and other adverse events. Keeping numerator and denominator together helps readers understand the scale of a count. A raw count in a larger cohort can be larger even when the proportion affected is not higher, so counts across cohorts should not be compared as if cohort sizes were equal. The posted data do not provide a randomized contrast that would make dose groups interchangeable for causal interpretation.

General statistical explanation: a confidence interval describes the uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval crossing a null value may be compatible with more than one interpretation. No confidence interval for the primary safety endpoint is reported in the registry record details, so precision cannot be judged from an interval estimate.

Why exposure and follow-up matter

General statistical explanation: event counts can be influenced by how long participants are observed and by how much time they spend receiving treatment. Time-to-event methods or exposure-adjusted rates can address some questions about differing observation time, but they answer different questions from a simple participant count. The registry lists a treatment period and follow-up extending up to 90 days after the last dose. It does not provide exposure-adjusted estimates in the reported safety information. A reader should not treat each cohort’s raw count as though all participants had identical exposure or follow-up.

The primary endpoint’s definition also matters. An event that begins after the first dose meets the timing criterion for treatment-emergent status, but timing alone is not a causal assessment. Seriousness is another classification and is not synonymous with treatment-emergent status. The safety summaries separate serious adverse events from other adverse events, while the primary endpoint is described more broadly as treatment-emergent adverse events.

Interpretation of dose cohorts

General statistical explanation: dose-escalation cohorts are commonly interpreted as stages of a development program, not as randomly assigned treatment groups. In a nonrandomized setting, observed differences may reflect dose, cohort composition, time, or other factors. In this study, the registry describes Phase 1 dose escalation until MTD or PAD was identified, but whether either was identified is not reported in the registry record. The dose-specific adverse-event counts therefore provide descriptive context, not an estimate of the causal effect of one dose versus another.

The record states that allocation is NA, masking is none, and the model is single group. Those design features limit comparative inference. There is no reported blinded comparison to reduce the potential for differences in event detection or assessment between treatment groups, and no randomized allocation to balance prognostic factors. This does not make the descriptive information unusable; it defines the narrower question the counts can answer.

Planning illustrations and inference

General statistical explanation: a sample-size calculation is a planning tool that relates a target effect, variability, significance level, and desired power to a required number of participants or events. A planning calculation based on an observed effect is not an estimate of how likely the completed study was to produce a statistically significant result. In particular, retrospective observed power does not replace confidence intervals or an analysis of the observed data.

The planning assumptions associated with this study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They define the target effect as a stated fraction of the observed effect. These assumptions are an illustration, not the registered single-group, nonrandomized trial design. The record does not report the trial’s own sample-size justification or provide a basis for treating such planning values as observed power.

General statistical explanation: over-dispersion arises when observed variability exceeds what a simple statistical model assumes. If a count model ignores over-dispersion, uncertainty can be understated and intervals or tests may be too optimistic. The registry information does not report a count-model analysis or an over-dispersion assessment for the primary endpoint. This is therefore a general consideration, not a claim about the analysis used in ECHO-203.

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("Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/k", "Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/", "Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/", "Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/", "Phase I : Epacadostat (100 mg) + Durvalumab (10 mg", "Phase I : Epacadostat (300 mg) + Durvalumab (10 mg")
n      <- c(6, 3, 4, 4, 8, 9)
events <- c(6, 3, 4, 4, 8, 9)
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  Phase I : Epacadostat (25 mg) + Durvalumab (3 mg/k  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase I : Epacadostat (25 mg) + Durvalumab (10 mg/  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Phase I : Epacadostat (50 mg) + Durvalumab (10 mg/  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  Phase I : Epacadostat (75 mg) + Durvalumab (10 mg/  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5
ARM  Phase I : Epacadostat (100 mg) + Durvalumab (10 mg  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  Phase I : Epacadostat (300 mg) + Durvalumab (10 mg  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes across Phase 1 and Phase 2: treatment-emergent adverse events, objective response rate, durability of response, progression-free survival, pharmacokinetic measures, and immunogenicity. Testing or estimating multiple outcomes can raise multiplicity concerns when formal claims are made. General statistical explanation: without a prespecified testing hierarchy or an adjustment strategy, repeated hypothesis tests can increase the chance of at least one apparently notable result arising by chance. The registry’s multiplicity strategy is not reported in the registry record.

The record lists 0 analyses. It does not report p-values, confidence intervals, model specifications, or a statistical testing plan for the outcomes described. It is therefore not possible to determine whether any formal multiplicity control was intended or applied. Nor is it possible to infer an analysis plan from the endpoint list alone.

The Phase 1 safety population is described as all subjects enrolled in the Phase 1 portion who received at least 1 dose of INCB024360 or MEDI4736. Treatment groups were determined according to the actual treatment received on Day 1, regardless of the actual study drug the subject re... The population description in the registry record is incomplete after that point. A Phase 2 analysis-population definition is not reported in the registry record.

Missing-data handling, withdrawals, endpoint-specific denominators, and the treatment of participants with incomplete follow-up are not reported in the registry record. These details matter because safety observations depend on who was followed and for how long. The total enrollment of 176 should not be assumed to be the denominator for every endpoint or dose cohort. The registry’s cohort-specific counts should be interpreted using their stated at-risk counts, without substituting the overall enrollment as a denominator.

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: abdominal pain (25.0%), bacteraemia (25.0%), fall (25.0%), hyponatraemia (25.0%), hypotension (25.0%).

The serious-adverse-event summaries are organized by treatment cohort and distinguish participants at risk from participants affected. The record also reports corresponding counts for other adverse events and lists deaths by cohort. These are participant counts, not measures of event rates adjusted for duration of exposure. Read each count in the context of its own cohort rather than treating the cohorts as equal-sized groups.

The serious-event terms listed in the record are abdominal pain, bacteraemia, fall, hyponatraemia, hypotension, and pyrexia, each with a reported value of 25.0%. The record does not clarify in this summary whether participants could appear under several terms, nor does it establish that these terms account for all serious events. The percentages should not be added together or interpreted as a complete distribution.

A serious adverse event is not necessarily an event caused by treatment. The registry counts do not, by themselves, establish relatedness or explain the circumstances of a death. The deaths listed by cohort should therefore be read as deaths recorded during the study, not as treatment-attributed deaths unless attribution is separately reported. Relatedness assessments and detailed event narratives are not reported in the registry record.

Because the study is single group and nonrandomized, differences in safety counts across dose cohorts cannot establish that one dose caused more or fewer events than another. Differences in cohort size and exposure also affect raw counts.

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

The posted results provide descriptive safety information from a Phase 1/2 study of epacadostat combined with durvalumab in selected advanced solid tumors. They identify the study’s treatment-emergent adverse-event endpoint and give cohort-level counts for serious and other adverse events, as well as deaths. The record also names serious adverse-event terms and reports their percentages. These registry entries can help readers understand what safety information was recorded and how it was organized.

They do not establish a causal effect of treatment on adverse events. Treatment-emergent status is based on timing after the first dose, while causality requires a separate assessment. The registry record does not provide enough detail in the posted summaries to attribute the listed events or deaths to study treatment.

These data also do not establish comparative efficacy. The study is listed as single group, allocation NA, and masking none; it is not a randomized comparison with a control group. The registry lists response, durability, and progression-free survival as secondary outcomes, but their numerical results are not reported in the registry record details considered for this analysis. No conclusion about treatment benefit relative to another treatment can be drawn from the safety counts.

Similarly, the cohort counts do not establish a dose-response relationship. Cohort sizes and treatment exposure differ, and participants were not randomly allocated among dose levels. The counts may be useful for describing the study experience, but comparisons across those cohorts are not controlled estimates of the effect of dose.

General statistical explanation: an estimate is most informative when its population, denominator, observation period, and uncertainty are clear. The registry provides a Phase 1 safety-population description and a stated endpoint timeframe, but does not report a complete uncertainty analysis for the primary outcome. Readers should distinguish what the record describes from what it does not establish: safety counts are present, while causal attribution, comparative efficacy, and the trial’s detailed inferential plan are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early clinical development: dose cohorts can generate important descriptive safety information without being suitable for direct causal comparisons. ECHO-203 is registered as a Phase 1/2, single-group study, with allocation listed as NA and no masking. The registry describes dose escalation in Phase 1 and specific dose cohorts in Phase 2. That structure helps explain why the adverse-event summaries are presented by cohort, but it does not create a randomized control comparison.

The distinction between a participant count and an event rate is also important. The primary endpoint is defined in terms of participants with treatment-emergent adverse events, while the adverse-event summaries separately report participants affected by serious and other events. These measures can describe observed events, but interpretation depends on the cohort denominator, the event definition, and the time during which participants were observed. The stated follow-up period extends up to 90 days after the last dose.

The registry’s secondary outcomes span response, time-to-event outcomes, pharmacokinetics, and immunogenicity. Such a range of outcomes can answer different scientific questions, but each requires its own definition and analysis population. Multiplicity procedures and the detailed statistical plan are not reported in the registry record, so formal claims across the outcomes cannot be evaluated from the record information available.

The study is therefore statistically informative as a record of a dose-escalation program and its reported safety categories, while also demonstrating the limits of nonrandomized cohort summaries. Keeping descriptive counts separate from causal and comparative claims is essential when interpreting studies of this design.

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 a complete result for the primary endpoint as a single overall estimate with an uncertainty interval. It includes cohort-level safety counts, but does not provide enough information in the posted summaries to determine the precision of the overall treatment-emergent adverse-event estimate.

The study is single group, allocation is listed as NA, and masking is none. The dose cohorts are not randomized control groups, so their results do not support a like-for-like efficacy or safety comparison. Differences among cohorts may reflect factors other than dose, and raw counts are affected by cohort size and observation time.

The record does not report event attribution, detailed descriptions of deaths, missing-data handling, withdrawal patterns, or endpoint-specific analysis denominators beyond the stated safety summaries. The Phase 1 safety-population description is incomplete in the registry record, and the Phase 2 analysis population is not reported in the registry record. Sample-size justification, detailed statistical methods, and multiplicity procedures are also not reported in the registry record.

The registry lists efficacy and other secondary outcomes, but their numerical results are not available in the record information. The listed serious adverse-event terms and percentages lack enough contextual detail to determine whether categories overlap or how they relate to the full set of serious events. These limitations restrict interpretation to descriptive statements about the information recorded, without causal attribution or comparative conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203) — NCT02318277.
• Registry record last updated 2022-01-13; status last verified 2022-01.
• Results first posted 2020-12-29.
• 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

ECHO-203 (NCT02318277) is a completed Phase 1/2, single-group study of epacadostat (INCB024360) combined with durvalumab (MEDI4736) in selected advanced solid tumors. The registry lists enrollment of 176, no masking, and allocation as NA. The study started on 2015-01-05, with primary completion on 2019-08-28.

The primary Phase 1 endpoint is the number of participants with treatment-emergent adverse events, defined by first occurrence or worsening after the first dose. The registry reports cohort-level serious and other adverse-event counts and deaths, and lists secondary outcomes covering response, durability, progression-free survival, pharmacokinetics, and immunogenicity. A randomized control comparison, full primary-endpoint uncertainty analysis, detailed statistical plan, and multiplicity strategy are not reported in the registry record.