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 Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers (NCT02178722), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02178722 |
| Phase | Phase 1, Phase 2 |
| Condition | Microsatellite-instability (MSI) High Colorectal Cancer (CRC), Endometrial Cancer, Head and Neck Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 444 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Incyte Corporation |
| Results posted | Yes |
2. Clinical Question
Population
Participants with selected cancers, including microsatellite-instability (MSI) high colorectal cancer, endometrial cancer, head and neck cancer, hepatocellular carcinoma, gastric cancer, lung cancer, lymphoma, renal cell carcinoma, ovarian cancer, solid tumors, urothelial cancer, melanoma, bladder cancer, and triple negative breast cancer. The safety evaluable population included enrolled participants who received at least one dose of pembrolizumab or epacadostat.
Intervention
Combination treatment with MK-3475 and INCB024360. The Phase 1 starting dose for INCB024360 was 25 mg twice a day, with dose escalation to determine the recommended Phase 2 dose. Phase 2 used the recommended dose.
Comparator
There was no randomized control group. The registry describes a non-randomized, parallel-arm study without masking. Dose groups and cancer cohorts are not randomized treatment comparisons.
Primary question
In Phase 1, what proportion of participants experienced treatment-emergent adverse events, including serious treatment-emergent adverse events, during the reported timeframe of approximately 54 months? The study also set out to assess safety, tolerability, and efficacy of the combination.
The clinical question combines a safety-focused dose-escalation phase with a later phase using the recommended Phase 2 dose. The registry lists a broad range of cancer types rather than a single disease population. That breadth is relevant to interpretation: overall safety counts describe the enrolled safety population, while they do not by themselves establish whether risks or responses were similar across cancer types. The registry record does not report cancer-specific outcome estimates in the posted results.
3. Trial Design
This was a Phase 1/2, non-randomized, unmasked, parallel study sponsored by Incyte Corporation. The record reports enrollment of 444 participants and a completed status. The study began on 2014-07-17, and primary completion was 2018-11-26. Its stated purpose was to assess the safety, tolerability, and efficacy of MK-3475 in combination with INCB024360 among participants with selected cancers.
Phase 1 evaluated the combination while escalating the INCB024360 dose. The starting dose was 25 mg twice a day, and dose escalation continued until a recommended Phase 2 dose was determined. The listed Phase 1 cohorts received epacadostat at 25 mg, 50 MG, 100 MG, and 300 MG BID. Phase 2 used the recommended Phase 2 dose; the listed Phase 2 cohort received epacadostat 100 MG BID. Pembrolizumab and epacadostat are the drug names used in the safety population description and cohort labels, alongside the study codes MK-3475 and INCB024360.
Because allocation was non-randomized and masking was absent, the cohort counts are descriptive. Differences between dose cohorts cannot be interpreted as effects of dose alone: the registry record does not establish that participants in different cohorts were comparable in their cancer type, disease status, or other prognostic characteristics. Nor is a dose cohort a like-for-like control group. The record does not report the detailed assignment process, eligibility criteria, or dose-escalation decision rules.
The listed secondary outcomes include duration of response, progression-free survival, duration of disease control, overall survival, ordinal categorical response score, and treatment-emergent adverse events in Phase 2. Although these outcomes are listed, their analysis results are not reported in the registry record. A protocol-level statistical analysis plan and sample-size justification are also not reported in the registry record.
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: Prior to 17May18 study amended/discontinued, 444 participants were enrolled. Survival follow up and monotherapy option after discontinuation of combination were removed so anyone in survival follow up were discontinued the study and were assigned to "study terminated by sponsor" because completed was not an option in the database for those in survival follow up. 1 patient on combo treatment did not move to the monotherapy so they were also assigned to this reason for discontinuing.
Overall Study
| Stage | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 mg BID | Phase 1: Epacadostat 100 mg BID | Phase 1: Epacadostat 300 mg BID | Phase 2: Epacadostat 100 mg BID |
|---|---|---|---|---|---|
| STARTED | 4 | 20 | 18 | 20 | 382 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 20 | 18 | 20 | 382 |
Reasons for not completing this period:
| Reason | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 mg BID | Phase 1: Epacadostat 100 mg BID | Phase 1: Epacadostat 300 mg BID | Phase 2: Epacadostat 100 mg BID |
|---|---|---|---|---|---|
| Withdrawal by Subject | 0 | 0 | 0 | 2 | 33 |
| Death | 2 | 13 | 12 | 12 | 205 |
| Lost to Follow-up | 0 | 0 | 0 | 2 | 11 |
| Study terminated by Sponsor | 2 | 7 | 6 | 4 | 128 |
| Physician Decision | 0 | 0 | 0 | 0 | 3 |
| Other | 0 | 0 | 0 | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).
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: The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).
| Characteristic | Unit | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 mg BID | Phase 1: Epacadostat 100 mg BID | Phase 1: Epacadostat 300 mg BID | Phase 2: Epacadostat 100 mg BID | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 4 | 20 | 18 | 20 | 382 | 444 | |
| Age, Continuous | years | 48.8 (SD 18.01) | 60.8 (SD 12.97) | 63.2 (SD 13.67) | 59.2 (SD 13.06) | 62.7 (SD 11.60) | 62.3 (SD 11.92) |
| Sex: Female, Male: Female | Participants | 3 | 9 | 6 | 9 | 181 | 208 |
| Sex: Female, Male: Male | Participants | 1 | 11 | 12 | 11 | 201 | 236 |
| Race/Ethnicity, Customized: White/Caucasian | Participants | 1 | 20 | 18 | 17 | 337 | 393 |
| Race/Ethnicity, Customized: Black/African-American | Participants | 1 | 0 | 0 | 2 | 19 | 22 |
| Race/Ethnicity, Customized: Asian | Participants | 1 | 0 | 0 | 1 | 15 | 17 |
| Race/Ethnicity, Customized: Native Hawaiian/Pacific Islander | Participants | 1 | 0 | 0 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 0 | 0 | 0 | 9 | 9 |
| Race/Ethnicity, Customized: Missing | Participants | 0 | 0 | 0 | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 0 | 0 | 1 | 1 | 16 | 18 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 4 | 20 | 17 | 19 | 353 | 413 |
| Race/Ethnicity, Customized: Unknown | Participants | 0 | 0 | 0 | 0 | 10 | 10 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 0 | 0 | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Missing | Participants | 0 | 0 | 0 | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events, measured over Approximately 54 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary Phase 1 endpoint is the percentage of participants with treatment-emergent adverse events (TEAE) and serious treatment-emergent adverse events. A TEAE is defined in the registry as an adverse event first reported, or a pre-existing event that worsened, after the first dose of study drug. The record defines a serious adverse event by its consequences or clinical significance, including fatal or life-threatening events, persistent or significant disability, congenital anomaly or birth defect, events requiring inpatient hospitalization or prolonging hospitalization, or clinically meaningful events that jeopardize the participant or may require intervention to prevent those outcomes.
Safety outcomes are important in dose-escalation research because decisions about further study depend on understanding the harms observed during exposure. Counts of participants with events convey how often an event category was recorded in the assessed population. They do not, by themselves, describe event severity beyond the registry's serious-event classification, timing, duration, recurrence, or causal relationship to study treatment.
The stated timeframe is approximately 54 months. The safety evaluable population includes all enrolled participants who received at least one dose of epacadostat or pembrolizumab. The endpoint is therefore defined around exposure and adverse-event reporting, rather than around a randomized comparison. The registry record does not report a Phase 1 efficacy endpoint result alongside these safety counts, and it does not provide event-level detail for the complete set of adverse events.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety counts describe adverse events in a non-randomized study population receiving the combination. Across the total safety group, 221 of 444 participants had a serious adverse event, and 434 of 444 had an event in the other adverse-event category. These are participant counts in the registry record, not estimates from a randomized comparison. They should be read as a description of events recorded in this study, not as evidence that the combination caused every event or that an alternative treatment would have produced fewer events.
The cohort counts vary in size. In Phase 1, the 25 mg BID group had 0 of 4 participants with a serious adverse event and 4 of 4 with an other adverse event. The 50 MG BID group had 8 of 20 with a serious adverse event and 18 of 20 with an other adverse event. The 100 MG BID group had 9 of 18 and 17 of 18, respectively; the 300 MG BID group had 9 of 20 and 20 of 20. The Phase 2 100 MG BID group had 195 of 382 with serious adverse events and 375 of 382 with other adverse events. The small Phase 1 cohort sizes mean that their counts are particularly limited in how precisely they characterize event frequency. These descriptive numbers do not establish a dose-response relationship.
Deaths are also recorded: the total group lists 250 deaths, with counts listed by cohort. These are not identified as deaths caused by treatment. The registry record does not report an attribution analysis that would distinguish deaths related to the study drugs from deaths due to cancer, other conditions, or other causes. The death counts therefore must not be treated as a treatment-effect estimate.
The registry lists sepsis at 10.0% among the top serious-event terms, malignant neoplasm progression at 8.6%, and anxiety, blood creatinine increased, cardiac failure, and colitis each at 5.6%. Those percentages describe the listed terms as recorded; the registry record does not provide enough information in these entries to establish their timing, overlap within participants, or causal attribution. A participant may experience more than one adverse event, so event-term percentages are not necessarily mutually exclusive.
No confidence intervals, p-values, adjusted comparisons, or efficacy analyses are reported in the registry record. Consequently, the posted safety counts support a descriptive account, but not a precise comparative estimate of treatment effect or a conclusion about efficacy. Results for the listed Phase 2 response and survival outcomes are not reported in the registry record.
9. Statistical Methods Explained
The primary outcome is binary at the participant level: the record classifies whether each participant experienced the relevant adverse-event category during the stated observation timeframe. A percentage is a way to express the number of participants with an event relative to the number assessed. The associated count and denominator matter because a percentage from a small cohort is generally less stable than a percentage based on a larger group. The cohort counts in this record differ substantially in size, so apparent differences between their event rates should not be interpreted as equally precise.
What does a confidence interval communicate?
In general, a confidence interval describes the uncertainty around an estimate under a specified statistical method. A narrow interval indicates greater precision than a wide interval, while neither width nor location alone removes bias from study design or incomplete reporting. No confidence intervals for the posted adverse-event counts are reported in the registry record. Without them, readers cannot use the record to judge the statistical precision of the group-specific event estimates beyond considering their denominators.
Why does the design affect comparisons?
Randomization is a method for assigning participants to groups so that, on average, prognostic factors are balanced by the assignment process. This study was non-randomized. Its dose groups therefore cannot be treated as exchangeable arms of a controlled experiment. Participants may differ across cohorts for reasons that are not recorded in the outcome counts, including disease mix or other clinical characteristics. Parallel groups in a non-randomized study do not automatically provide a causal contrast. The record reports no adjustment method that would address such differences.
Masking was listed as none. In general, masking can reduce the influence of treatment knowledge on care, assessment, or reporting, depending on the outcome and study procedures. Adverse events include participant reports and clinical judgments, so the absence of masking is relevant context. The registry record does not describe procedures to limit potential assessment or reporting effects.
How should the adverse-event categories be read?
The endpoint separates serious treatment-emergent adverse events from other adverse events. The registry definitions specify what qualifies as treatment-emergent and serious. The posted group counts describe participants recorded in these categories; they do not provide the full event-level distribution. They also do not state whether each participant contributed to both categories, so the counts should not be added or treated as mutually exclusive. The registry record does not report event duration, recurrent-event methods, exposure-adjusted rates, or the approach to attributing an event to treatment.
The safety population is defined as enrolled participants who received at least one dose of either study drug. This is an exposure-based population for the safety outcome. It is distinct from a population defined by random assignment, since there was no random allocation. The registry record does not report further rules for handling participants with incomplete follow-up, early discontinuation, or missing event information.
What does the planning illustration represent?
The sample-size material is described as a planning illustration based on an observed effect, not as the study's original design justification. Its stated assumptions are 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. Such calculations can illustrate how a hypothetical future comparison might depend on the assumed effect and analysis choices. They do not establish the actual sample-size rationale for this trial, and they are not observed power. The registry record does not report the trial's own sample-size justification or the assumptions used to plan enrollment.
In general, over-dispersion means that observed variability is greater than a statistical model expects. It can make standard errors too small if a model assumes less variability than the data contain. That concern is more directly relevant to certain count or clustered outcomes than to a simple participant-level binary endpoint. The posted primary endpoint is a percentage, and the registry record does not report a model-based analysis or an assessment of over-dispersion for it. No model can therefore be attributed to the posted primary outcome results.
What analyses are available?
The registry record lists no analysis entries. It does not report estimates, standard errors, p-values, confidence intervals, covariate adjustment, or hypothesis tests for the adverse-event endpoint. The outcome counts can be described directly, but additional inferential results should not be inferred from them. In particular, a difference between cohort counts or percentages would not itself show that a dose caused a change in risk.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes, including response duration, progression-free survival, duration of disease control, overall survival, ordinal categorical response score, and treatment-emergent adverse events in Phase 2. Evaluating many outcomes can raise a multiplicity concern: when several hypotheses are tested, the chance of at least one apparently notable result can increase. General approaches include prespecifying a primary comparison, controlling an overall error rate, or treating outcomes as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or an analysis plan specifying how results were to be interpreted.
Missing-data handling is also not reported in the registry record. The safety population includes participants who received at least one dose, but that definition alone does not explain how incomplete adverse-event observation or missing outcome assessments were handled. For response and time-to-event outcomes, the record would need to specify how follow-up, censoring, and unavailable assessments were addressed to support a detailed analysis interpretation. Those methods are not reported in the registry record.
The population definition is explicit for the primary safety outcome: enrolled participants who received at least one dose of epacadostat or pembrolizumab. The record does not report the analysis populations used for the listed Phase 2 efficacy outcomes, or whether all enrolled participants contributed to each secondary outcome. Since allocation was non-randomized, there is no intention-to-treat population based on randomized assignment described in this record. The posted counts should therefore be interpreted using the stated safety population and not assumed to represent every enrolled participant under a different analysis rule.
These gaps limit reproducibility and the assessment of selective reporting. They do not prove that a multiplicity method or missing-data procedure was not used in practice; they mean that such procedures 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 |
|---|---|---|---|
| Phase 1: Epacadostat 25 mg BID | 0 | 4 | 0.0% |
| Phase 1: Epacadostat 50 MG BID | 8 | 20 | 40.0% |
| Phase 1: Epacadostat 100 MG BID | 9 | 18 | 50.0% |
| Phase 1: Epacadostat 300 MG BID | 9 | 20 | 45.0% |
| Phase 2: Epacadostat 100 MG BID | 195 | 382 | 51.0% |
| Total | 221 | 444 | 49.8% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase 1: Epacadostat 25 mg BID | 2 of 4 |
| Phase 1: Epacadostat 50 MG BID | 13 of 20 |
| Phase 1: Epacadostat 100 MG BID | 12 of 18 |
| Phase 1: Epacadostat 300 MG BID | 14 of 20 |
| Phase 2: Epacadostat 100 MG BID | 209 of 382 |
| Total | 250 of 444 |
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 |
|---|---|
| Phase 1: Epacadostat 25 mg BID | 4 of 4 |
| Phase 1: Epacadostat 50 MG BID | 18 of 20 |
| Phase 1: Epacadostat 100 MG BID | 17 of 18 |
| Phase 1: Epacadostat 300 MG BID | 20 of 20 |
| Phase 2: Epacadostat 100 MG BID | 375 of 382 |
| Total | 434 of 444 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 MG BID | Phase 1: Epacadostat 100 MG BID | Phase 1: Epacadostat 300 MG BID | Phase 2: Epacadostat 100 MG BID | Total |
|---|---|---|---|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 4 | 1 of 20 | 1 of 18 | 0 of 20 | 33 of 382 | 35 of 444 |
| Pneumonia | Infections and infestations | 0 of 4 | 0 of 20 | 0 of 18 | 1 of 20 | 15 of 382 | 16 of 444 |
| Abdominal pain | Gastrointestinal disorders | 0 of 4 | 1 of 20 | 0 of 18 | 1 of 20 | 12 of 382 | 14 of 444 |
| Nausea | Gastrointestinal disorders | 0 of 4 | 0 of 20 | 0 of 18 | 1 of 20 | 12 of 382 | 13 of 444 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 0 of 4 | 0 of 20 | 0 of 18 | 1 of 20 | 11 of 382 | 12 of 444 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 4 | 1 of 20 | 0 of 18 | 1 of 20 | 9 of 382 | 11 of 444 |
| Small intestinal obstruction | Gastrointestinal disorders | 0 of 4 | 0 of 20 | 0 of 18 | 0 of 20 | 11 of 382 | 11 of 444 |
| Disease progression | General disorders | 0 of 4 | 1 of 20 | 0 of 18 | 0 of 20 | 9 of 382 | 10 of 444 |
| Sepsis | Infections and infestations | 0 of 4 | 0 of 20 | 0 of 18 | 2 of 20 | 8 of 382 | 10 of 444 |
| Vomiting | Gastrointestinal disorders | 0 of 4 | 0 of 20 | 0 of 18 | 1 of 20 | 9 of 382 | 10 of 444 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase 1: Epacadostat 25 mg BID | Phase 1: Epacadostat 50 MG BID | Phase 1: Epacadostat 100 MG BID | Phase 1: Epacadostat 300 MG BID | Phase 2: Epacadostat 100 MG BID | Total |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 3 of 4 | 13 of 20 | 9 of 18 | 13 of 20 | 185 of 382 | 223 of 444 |
| Nausea | Gastrointestinal disorders | 3 of 4 | 9 of 20 | 5 of 18 | 11 of 20 | 115 of 382 | 143 of 444 |
| Cough | Respiratory, thoracic and mediastinal disorders | 3 of 4 | 7 of 20 | 3 of 18 | 9 of 20 | 100 of 382 | 122 of 444 |
| Diarrhoea | Gastrointestinal disorders | 3 of 4 | 5 of 20 | 7 of 18 | 5 of 20 | 99 of 382 | 119 of 444 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 4 | 4 of 20 | 1 of 18 | 9 of 20 | 95 of 382 | 109 of 444 |
| Constipation | Gastrointestinal disorders | 3 of 4 | 8 of 20 | 4 of 18 | 3 of 20 | 86 of 382 | 104 of 444 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 4 | 6 of 20 | 1 of 18 | 6 of 20 | 86 of 382 | 101 of 444 |
| Pruritus | Skin and subcutaneous tissue disorders | 3 of 4 | 6 of 20 | 2 of 18 | 9 of 20 | 78 of 382 | 98 of 444 |
| Vomiting | Gastrointestinal disorders | 1 of 4 | 4 of 20 | 4 of 18 | 10 of 20 | 78 of 382 | 97 of 444 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 4 of 4 | 9 of 20 | 4 of 18 | 6 of 20 | 64 of 382 | 87 of 444 |
Serious events with the highest arm-level rate: sepsis (10.0%), malignant neoplasm progression (8.6%), anxiety (5.6%), blood creatinine increased (5.6%), cardiac failure (5.6%).
The total safety group includes 444 participants. The registry records serious adverse events in 221 participants and other adverse events in 434 participants. Read these as numbers of participants with events in the categories used by the record, not as counts of individual event episodes. A participant can experience multiple events, and the record does not state whether the serious and other categories overlap at the participant level.
The cohort counts are also descriptive. The smaller Phase 1 cohorts include 4 participants at 25 mg BID, 20 at 50 MG BID, 18 at 100 MG BID, and 20 at 300 MG BID; the Phase 2 100 MG BID cohort includes 382 participants. A count such as 0 serious events among 4 participants in the 25 mg BID cohort does not demonstrate that the risk is absent. Small groups leave substantial uncertainty about the frequency that could occur in a broader population. No interval estimates are reported in the registry record to quantify that uncertainty.
The 250 deaths in the total group are recorded as a count. The registry record does not identify them as treatment-related, so they must not be interpreted as deaths caused by either study drug. The listed serious-event terms and percentages likewise describe recorded events, not proof of drug causation. These figures do not replace information about event timing, severity beyond the serious classification, exposure duration, or clinical review, which is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record documents a Phase 1/2 investigation of MK-3475 plus INCB024360 across selected cancers, with Phase 1 dose escalation and Phase 2 treatment at the recommended dose. Its posted primary outcome is a safety measure. The total counts show that serious and other adverse events were recorded among participants in the safety population, while the cohort counts describe how those records were distributed across the listed dose groups. This is a descriptive account of the study population, not a controlled estimate of harm relative to another treatment.
The record does not establish that every event was caused by study treatment. It does not establish that a higher dose led to more events, because the dose cohorts were not randomized comparisons and may differ in other ways. Nor do the death counts establish treatment-related mortality. The absence of reported confidence intervals, hypothesis tests, or adjusted estimates means the posted information does not quantify comparative uncertainty using those methods.
The study was also intended to assess efficacy, and the registry lists response, disease-control, progression-free survival, and overall-survival outcomes. However, outcome results for these measures are not reported in the registry record. The safety counts therefore cannot answer whether the combination improved cancer outcomes, and they do not support claims that treatment did or did not work.
These limits do not make the record uninformative. It identifies the study design, the safety population definition, the dose cohorts, and the recorded adverse-event counts. They define what can be said: adverse events were reported in the enrolled, treated population under the registry's definitions. More detailed interpretation would require outcome estimates with uncertainty, fuller event and follow-up information, and a clear account of analytic methods. Those details are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines dose escalation with a later Phase 2 cohort while enrolling participants across a broad range of cancer types. Those features make the safety counts useful as a description of the study experience, but they also make pooled summaries difficult to interpret as if they came from a uniform population. The registry record does not provide cancer-specific safety estimates or efficacy results that would show how outcomes varied among the listed conditions.
The non-randomized design is central to the statistical reading. Dose groups can describe experience at the listed doses, but they do not provide a like-for-like control comparison. Cohort size also varies, so the precision behind the observed counts is not uniform. These design features are reasons to separate descriptive safety reporting from causal claims about dose or treatment effect.
The registry record further illustrates the distinction between an outcome being named and its analysis being reported. Several efficacy outcomes are listed, yet their results and analysis methods are not reported in the registry record. A well-defined list of outcomes does not supply estimates, uncertainty intervals, missing-data procedures, or multiplicity control. Readers need those elements to assess how firmly a result supports an inference.
Finally, the sample-size material is explicitly a planning illustration based on an observed effect, rather than the trial's own planning rationale. Keeping that distinction clear prevents a hypothetical calculation from being mistaken for evidence about the study's design adequacy or observed statistical power. Together, these points make the record useful for understanding what was studied and what safety counts were posted, while setting clear boundaries on causal and efficacy interpretation.
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 registry record offers limited detail for interpreting the posted safety counts. It does not report confidence intervals, hypothesis tests, adjusted analyses, or a statistical analysis plan. The absence of these details means that the precision and inferential status of the adverse-event estimates cannot be assessed from the record. It also does not report how missing safety information, incomplete follow-up, or treatment discontinuation was handled.
The study was non-randomized and unmasked. As a result, dose cohorts do not function as concurrent randomized controls, and observed differences can reflect population composition or other factors as well as dose. The record does not describe allocation procedures or give cohort-level characteristics needed to evaluate comparability. The broad range of cancer conditions further limits what can be inferred from pooled counts without disease-specific summaries.
The adverse-event reporting is not a complete clinical account. The record gives participant counts for serious and other events and lists selected serious-event terms, but does not report full event-level data, timing, duration, recurrent events, exposure-adjusted rates, or attribution to treatment. The deaths are counts without a reported causal classification. The percentages for selected terms should not be interpreted as mutually exclusive or as causal estimates.
Although efficacy outcomes are listed, results for response and survival measures are not reported in the registry record. The record also does not report multiplicity control, analysis populations for those outcomes, or missing-data and censoring methods. Finally, the sample-size material is a planning illustration, not a documented justification for the enrollment target. These omissions limit reproducibility and the scope of conclusions that can be drawn from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers — NCT02178722.
- Registry record last updated 2022-02-14; status last verified 2022-02.
- Results first posted 2019-12-19.
- 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
NCT02178722 is a completed, non-randomized Phase 1/2 study of MK-3475 with INCB024360 in participants with selected cancers. The study enrolled 444 participants and used dose escalation in Phase 1 to determine the recommended Phase 2 dose. The Phase 1 starting dose was 25 mg twice a day; the listed Phase 2 cohort received epacadostat 100 MG BID.
The primary Phase 1 outcome concerns treatment-emergent and serious treatment-emergent adverse events over approximately 54 months. In the total safety group, the record lists serious adverse events in 221 participants, other adverse events in 434 participants, and 250 deaths. The record does not identify the deaths as treatment-related.
Phase 2 response and survival outcomes are listed, but their results are not reported in the registry record. No analysis entries are listed. The safety counts are descriptive and do not provide a randomized comparison or establish treatment causation.