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 of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062) (NCT03099161), a non-randomized phase 1 study. The primary outcome is Number of Participants With Dose-limiting Toxicities (DLTs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03099161 |
| Phase | Phase 1 |
| Condition | Neoplasm |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned participants with advanced solid tumors or advanced malignancies that had not responded to prior therapy. The primary endpoint population comprised participants who received at least one dose of study treatment in Cycle 1 and were observed for safety or experienced a dose-limiting toxicity during that cycle. Further eligibility details are not reported in the registry record.
Intervention
Preladenant was evaluated as a single agent at 25 mg twice a day and 50 mg twice a day, and at 25 mg twice a day in combination with pembrolizumab 200 mg. Treatment was described in 21-day cycles, with Cycle 1 used for dose-limiting toxicity assessment. The study aimed to identify and confirm a recommended Phase 2 dose.
Comparator
The registry classifies allocation as non-randomized and masking as none. The treatment arms therefore should not be read as randomized, like-for-like comparisons. No concurrent control group is identified in the registry record, and the record does not report an allocation procedure that would make the groups exchangeable.
Primary question
The primary endpoint asks how many participants experienced dose-limiting toxicities during Cycle 1, which lasted up to 21 days. This endpoint was used to evaluate early safety and inform dose selection. The numerical primary-endpoint results are not reported in the registry record, so the safety counts cannot establish the number of participants meeting the dose-limiting toxicity definition.
3. Trial Design
This was a non-randomized, unmasked, parallel-arm study registered as PHASE1. The registry lists an enrollment of 10 and a status of terminated. The recorded start date is 2017-06-27, and the primary completion date is 2017-11-24. Those record-level details describe the registered study but do not explain why enrollment ended or why the study was terminated; that information is not reported in the registry record.
The intervention descriptions cover preladenant alone at 25 mg twice a day and 50 mg twice a day, as well as preladenant 25 mg twice a day combined with pembrolizumab 200 mg. The regimens were described for 21-day cycles, with treatment continuing for a maximum of 35 cycles in the arm descriptions. In the initial dose evaluation phase, the study was intended to establish a recommended Phase 2 dose based on dose-limiting toxicities at each dose level. The brief summary also describes a second part intended to evaluate safety and efficacy of the combination at that dose in participants with select solid tumors.
Because treatment allocation was not randomized, any differences across arms could reflect participant characteristics, dose level, treatment combination, or other factors, rather than treatment alone. The registry does not report arm-specific baseline characteristics or an adjusted comparative analysis. The groups should therefore be read as separate experiences in a dose-evaluation study, not as arms of a controlled efficacy comparison.
The title describes a Phase Ib/II study, while the structured phase entry is PHASE1. This record-level distinction does not establish that the later planned study part was completed. The study is listed as terminated, and the registry record does not report the reason for termination or whether all planned parts and objectives were carried out.
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: This study was planned to have 2 parts: a dose escalation/confirmation phase (Part 1) and an expansion phase (Part 2). The expansion phase was not conducted due to early study termination.
Overall Study
| Stage | Preladenant 25 mg Twice a Day (BID) | Preladenant 50 mg BID | Preladenant 25 mg BID + Pembrolizumab 200 mg |
|---|---|---|---|
| STARTED | 3 | 4 | 3 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 4 | 3 |
Reasons for not completing this period:
| Reason | Preladenant 25 mg Twice a Day (BID) | Preladenant 50 mg BID | Preladenant 25 mg BID + Pembrolizumab 200 mg |
|---|---|---|---|
| Adverse Event | 0 | 0 | 2 |
| Physician Decision | 2 | 0 | 0 |
| Progressive Disease | 1 | 4 | 1 |
Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study treatment in Cycle 1 (21-day Cycle) and were observed for safety or experienced a DLT 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.
Population: All enrolled participants
| Characteristic | Unit | Preladenant 25 mg BID | Preladenant 50 mg BID | Preladenant 25 mg BID + Pembrolizumab 200 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 4 | 3 | 10 | |
| Age, Continuous | Years | 61.3 (SD 10.8) | 40.3 (SD 16.3) | 41.3 (SD 18.5) | 46.9 (SD 17.0) |
| Sex: Female, Male: Female | Participants | 2 | 2 | 1 | 5 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 2 | 5 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 3 | 4 | 3 | 10 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): ECOG PS=0 | Participants | 2 | 2 | 2 | 6 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): ECOG PS=1 | Participants | 1 | 2 | 1 | 4 |
| Prior Line of Therapy: First Line | Participants | 2 | 2 | 0 | 4 |
| Prior Line of Therapy: Second Line | Participants | 0 | 2 | 3 | 5 |
| Prior Line of Therapy: Third Line | Participants | 0 | 0 | 0 | 0 |
| Prior Line of Therapy: Fourth Line | Participants | 1 | 0 | 0 | 1 |
| Prior Line of Therapy: Fifth Line | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Dose-limiting Toxicities (DLTs), measured over Cycle 1 (up to 21 days).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with dose-limiting toxicities during Cycle 1, up to 21 days. A count endpoint records how many participants in the defined safety population met the study's dose-limiting toxicity criteria. The primary population includes participants who received at least one dose in Cycle 1 and were observed for safety or experienced a dose-limiting toxicity during that cycle.
The criteria used National Cancer Institute Common Terminology Criteria for Adverse Events version 4. They included specified severe hematologic and non-hematologic toxicities, certain laboratory abnormalities, febrile neutropenia, treatment interruption or delay due to treatment-related toxicity, missing more than 25% of preladenant doses because of adverse events during Cycle 1, and Grade 5 toxicity. The registry gives detailed thresholds for these events. These criteria make the endpoint a rule-based count rather than a general measure of all adverse events.
In early dose evaluation, dose-limiting toxicities are used to identify whether a dose has sufficiently concerning toxicity during the prespecified assessment period to affect dose selection. The endpoint does not by itself describe all later safety experience, nor does it measure tumor response. The registry record gives the endpoint definition and timeframe, but the number of participants meeting the definition is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main interpretive constraint is that the registry record does not report numerical results for the primary endpoint. It therefore does not show how many participants had dose-limiting toxicities in Cycle 1 at any of the listed regimens. The adverse-event summaries are not substitutes for that endpoint: a serious adverse event or another adverse event is not necessarily a dose-limiting toxicity under the study's specific criteria, and a dose-limiting toxicity need not be represented by a single event term in the summaries.
The record lists serious adverse events affecting 2 of 3 participants in the preladenant 25 mg BID group, 1 of 4 in the preladenant 50 mg BID group, and 2 of 3 in the preladenant 25 mg BID plus pembrolizumab 200 mg group. It also reports other adverse events affecting 3 of 3, 4 of 4, and 3 of 3 participants, respectively. These are descriptive counts from non-randomized groups. They do not establish that one regimen caused more or fewer events than another, because allocation was not randomized and the groups are not like-for-like controls.
The record lists deaths of 2, 2, and 0 across those same groups. The death counts are not accompanied by a cause-of-death analysis or an account of attribution in the information available in the registry record. They should not be interpreted as treatment-related deaths without that information. Similarly, the serious-event terms and their percentages describe recorded events but do not, by themselves, establish causation or comparative risk.
The study description identifies objective response rate under RECIST 1.1 as a secondary outcome, and describes a preliminary efficacy objective. Numerical response results are not reported in the registry record. There are also no reported inferential analyses: the record lists zero analyses. Thus, the available information does not support a treatment-effect estimate, a confidence interval, or a formal comparison of efficacy between regimens.
The enrollment of 10 and terminated status provide context for the record, but they do not explain the completeness or representativeness of the outcome data. The reason for termination, any recruitment constraints, and the number assessed for each endpoint are not reported in the registry record. Conclusions should remain limited to the registered design and the descriptive safety counts that are recorded.
9. Statistical Methods Explained
The central design feature is non-random allocation. Participants were assigned to treatment groups without randomization, and masking was recorded as none. In general, randomization helps balance known and unknown participant characteristics across treatment groups. Without it, observed differences can arise from the way participants entered or were assigned to groups, as well as from treatment. The registry record does not describe an adjustment method that would address this concern, so arm-to-arm differences should be interpreted descriptively.
What does the primary count represent?
The primary endpoint is a count of participants meeting a prespecified dose-limiting toxicity definition during Cycle 1. It is not a continuous measurement or a time-to-event outcome. The endpoint's population is restricted to participants who received at least one dose in Cycle 1 and were observed for safety or experienced a dose-limiting toxicity during that cycle. This population definition matters: a count cannot be interpreted without knowing who was eligible to contribute to it and how incomplete observation was handled. The registry record defines the population but does not report the endpoint count or the number analyzed for it.
The dose-limiting toxicity definition combines clinical events, laboratory criteria, treatment interruptions, and a threshold for missed preladenant doses because of adverse events. It is a study-specific operational rule, applied using National Cancer Institute Common Terminology Criteria for Adverse Events version 4. The rule was intended for early safety and dose evaluation. It is narrower than a count of every adverse event and should not be equated with the serious adverse-event summary.
Why does the design affect interpretation?
For a randomized comparison, allocation is intended to make treatment groups comparable apart from the assigned intervention. That protection is absent in this non-randomized design. The doses and combination regimen also differ across groups, so any observed difference would not isolate a single treatment contrast. A descriptive count can indicate what was recorded in each group, but it cannot, on its own, establish a causal effect. No randomized control comparison or adjusted model is reported in the registry record.
The study is described as having an initial dose evaluation phase and a planned later phase to examine the combination at the recommended Phase 2 dose. The available record does not establish how the planned dose decision was made in practice, whether a recommended dose was ultimately confirmed, or whether the later part was completed. Those details are not reported in the registry record.
What do statistical uncertainty and over-dispersion mean in general?
General statistical explanation: A confidence interval expresses the range of values reasonably compatible with observed data under a statistical model. It communicates precision, not certainty that a treatment effect is real, and its interpretation depends on the design and assumptions. No confidence interval for the primary endpoint or an arm comparison is reported in the registry record. A point count alone does not quantify how imprecise an estimate may be, particularly in small groups.
General statistical explanation: Over-dispersion occurs when count data vary more than a model expects. If it is ignored, standard errors can be too small and uncertainty can be understated. The primary outcome is a count of participants with an event, rather than a repeated event count per participant. The registry record does not report a model for the endpoint, an over-dispersion assessment, or an inferential analysis, so no claim about those procedures can be made.
How should planning illustrations be read?
The stated planning assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. Such planning values are hypothetical design aids, not observed trial outcomes or evidence of the study's achieved power. The registry record does not report that these assumptions were the study's original design rationale, nor does it provide a sample-size justification. The assumptions do not turn the non-randomized groups into a controlled comparison.
The record lists no analyses. It therefore does not document a test statistic, model, adjustment, or inferential result for the primary endpoint. The available numerical safety information is descriptive, and no new comparative statistic should be inferred from it.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Preladenant 25 mg BID | 3 | 0 | 0.0% | 0.0% to 70.8% | 0.0% to 56.1% | 0.6% to 60.2% |
| Preladenant 50 mg BID | 4 | 0 | 0.0% | 0.0% to 60.2% | 0.0% to 49.0% | 0.5% to 52.2% |
| Preladenant 25 mg BID + Pembrolizumab 200 mg | 3 | 0 | 0.0% | 0.0% to 70.8% | 0.0% to 56.1% | 0.6% to 60.2% |
R code and output
arm <- c("Preladenant 25 mg BID", "Preladenant 50 mg BID", "Preladenant 25 mg BID + Pembrolizumab 200 mg")
n <- c(3, 4, 3)
events <- c(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 Preladenant 25 mg BID 3 0 0.0 0.0 70.8 0.0 56.1 0.6 60.2
ARM Preladenant 50 mg BID 4 0 0.0 0.0 60.2 0.0 49.0 0.5 52.2
ARM Preladenant 25 mg BID + Pembrolizumab 200 mg 3 0 0.0 0.0 70.8 0.0 56.1 0.6 60.211. Multiplicity, Missing Data and Analysis Populations
The registry identifies objective response rate per RECIST 1.1 as a secondary outcome, alongside the primary dose-limiting toxicity count. It lists four outcome measures, but the numerical results for the primary endpoint and response outcome are not reported in the registry record. A multiplicity strategy for testing more than one outcome or making comparisons across regimens is also not reported in the registry record.
Multiplicity matters when several outcomes, dose groups, or treatment contrasts are examined. In general, conducting multiple statistical tests can increase the chance of at least one apparently notable result even when there is no underlying effect. Prespecified testing hierarchies or adjustments can address that issue, but no such procedure is described in the registry record. Since no analyses are listed, there are no reported test results to interpret in light of a multiplicity adjustment.
The primary endpoint population is defined by treatment receipt and safety observation or occurrence of a dose-limiting toxicity in Cycle 1. This is the only explicit analysis-population description in the registry record. A broader intention-to-treat population, a per-protocol population, or rules for handling participants with incomplete observation are not reported in the registry record.
Missing-data procedures are not reported in the registry record. The dose-limiting toxicity definition includes missing more than 25% of preladenant doses because of adverse events during Cycle 1 as one criterion, but that criterion is not a general missing-outcome method. The record does not say how missing toxicity assessments, early discontinuation for other reasons, or unavailable response assessments were handled. Consequently, completeness and potential bias from missing outcome information cannot be evaluated from the registry record.
12. 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 |
|---|---|---|---|
| Preladenant 25 mg BID | 2 | 3 | 66.7% |
| Preladenant 50 mg BID | 1 | 4 | 25.0% |
| Preladenant 25 mg BID + Pembrolizumab 200 mg | 2 | 3 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Preladenant 25 mg BID | 2 of 3 |
| Preladenant 50 mg BID | 2 of 4 |
| Preladenant 25 mg BID + Pembrolizumab 200 mg | 0 of 3 |
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 |
|---|---|
| Preladenant 25 mg BID | 3 of 3 |
| Preladenant 50 mg BID | 4 of 4 |
| Preladenant 25 mg BID + Pembrolizumab 200 mg | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Preladenant 25 mg BID | Preladenant 50 mg BID | Preladenant 25 mg BID + Pembrolizumab 200 mg |
|---|---|---|---|---|
| Liver function test increased | Investigations | 0 of 3 | 0 of 4 | 2 of 3 |
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | 1 of 3 | 0 of 4 | 0 of 3 |
| Dysphagia | Gastrointestinal disorders | 1 of 3 | 0 of 4 | 0 of 3 |
| Intestinal obstruction | Gastrointestinal disorders | 0 of 3 | 1 of 4 | 0 of 3 |
| Urinary tract infection | Infections and infestations | 0 of 3 | 0 of 4 | 1 of 3 |
| Kidney enlargement | Renal and urinary disorders | 0 of 3 | 1 of 4 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Preladenant 25 mg BID | Preladenant 50 mg BID | Preladenant 25 mg BID + Pembrolizumab 200 mg |
|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | 1 of 3 | 2 of 4 | 1 of 3 |
| Fatigue | General disorders | 1 of 3 | 2 of 4 | 1 of 3 |
| Nausea | Gastrointestinal disorders | 1 of 3 | 2 of 4 | 0 of 3 |
| Asthenia | General disorders | 1 of 3 | 2 of 4 | 0 of 3 |
| Vomiting | Gastrointestinal disorders | 0 of 3 | 2 of 4 | 0 of 3 |
| Oedema peripheral | General disorders | 2 of 3 | 0 of 4 | 0 of 3 |
| Aspartate aminotransferase increased | Investigations | 0 of 3 | 0 of 4 | 2 of 3 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 3 | 2 of 4 | 0 of 3 |
| Dizziness | Nervous system disorders | 0 of 3 | 1 of 4 | 1 of 3 |
| Anaemia | Blood and lymphatic system disorders | 0 of 3 | 0 of 4 | 1 of 3 |
Serious events with the highest arm-level rate: liver function test increased (66.7%), inappropriate antidiuretic hormone secretion (33.3%), dysphagia (33.3%), urinary tract infection (33.3%), intestinal obstruction (25.0%).
The serious adverse-event summaries report participants at risk and participants affected for each regimen. In the preladenant 25 mg BID group, 3 were at risk and 2 were affected; in the preladenant 50 mg BID group, 4 were at risk and 1 was affected; in the combination group, 3 were at risk and 2 were affected. The other-adverse-event summaries report 3 at risk and 3 affected, 4 at risk and 4 affected, and 3 at risk and 3 affected, respectively. These counts are descriptive and should not be read as a randomized comparison.
The registry lists serious-event terms including liver function test increased, inappropriate antidiuretic hormone secretion, dysphagia, urinary tract infection, intestinal obstruction, and kidney enlargement, with the corresponding percentages recorded in the adverse-event summary. The basis for those term-specific percentages is not explained in the registry record, so they should not be converted into participant counts or compared across terms without further denominator information.
Deaths are listed separately as 2, 2, and 0 across the three groups. The registry record does not report cause or treatment attribution for these deaths in the available summary. Serious adverse events, other adverse events, deaths, and the primary dose-limiting toxicity endpoint are distinct summaries and should not be treated as interchangeable measures.
13. What the Result Does, and Does Not, Mean
The record establishes that preladenant was evaluated alone at two dose levels and in combination with pembrolizumab in a non-randomized, unmasked, parallel-arm study of advanced tumors. Its primary safety question concerned dose-limiting toxicities during Cycle 1, with the stated aim of supporting recommended-dose selection. The registry also describes a planned evaluation of safety and efficacy for the combination, and identifies objective response rate as a secondary outcome.
The available record does not report the numerical primary-endpoint result or response-rate result. It therefore does not establish how many participants met the dose-limiting toxicity definition, what response outcomes occurred, or whether any regimen had a better outcome than another. The adverse-event and death counts are descriptive; because there was no randomized allocation, they do not support a causal comparison between groups. No inferential analyses are listed.
These absences are not evidence that an outcome did or did not occur. They mean that the relevant numerical outcome or analysis is not reported in the registry record. Similarly, a serious adverse event does not automatically qualify as a dose-limiting toxicity, and the dose-limiting toxicity count cannot be reconstructed from the serious-event terms.
The study is listed as terminated, but the reason and the extent to which planned objectives were completed are not reported in the registry record. The record therefore supports a description of the study's intended design and the adverse-event summaries, but not a conclusion about efficacy, comparative safety, or the final dose-selection decision.
14. Why This Trial Matters Statistically
This study illustrates the role of early safety endpoints in dose evaluation. A dose-limiting toxicity endpoint applies predefined rules to events observed during a specified early treatment period. That approach can inform dose selection, but its interpretation depends on the endpoint definition, the number observed, and the completeness of safety assessment. Here, the definition and Cycle 1 timeframe are recorded, while the primary numerical result is not reported in the registry record.
The study also highlights why treatment groups in a non-randomized dose evaluation should not be treated as direct controls for one another. The regimens differ, allocation was not randomized, and masking was absent. Descriptive safety counts remain useful for understanding what the record lists, but they cannot separate treatment effects from group differences or other influences.
A further statistical lesson is the distinction between a study objective and an observed result. The brief summary describes a preliminary efficacy objective and a planned objective response assessment, but the registry record does not report response results or analyses. Likewise, planning assumptions for sample-size illustrations do not demonstrate that the study was designed or powered for a particular comparison, and do not measure achieved power.
Finally, the terminated status and limited reported analysis information make completeness important to interpretation. Without the reason for termination, endpoint results, missing-data procedures, or analysis plan, readers cannot determine how fully the intended evaluations were carried out. The record is therefore most informative as a description of the registered early-phase design and the safety summaries it reports, rather than as a comparative efficacy assessment.
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 primary endpoint is defined, but its numerical result is not reported in the registry record. This prevents direct assessment of the dose-limiting toxicity experience by regimen and prevents confirmation of the dose-selection objective from the outcome data. The record also does not report numerical results for the secondary objective response outcome.
The non-randomized allocation and absence of masking limit comparative interpretation. The registry record does not report a concurrent control group or an adjusted analysis, and the treatment regimens differ across groups. The group-level adverse-event counts therefore cannot establish whether differences reflect treatment or other factors.
The study is listed as terminated, but the reason for termination and the extent to which the planned parts were completed are not reported in the registry record. The record does not explain whether the recommended Phase 2 dose was established or whether the planned later evaluation occurred. It also does not report baseline characteristics, endpoint-specific numbers analyzed, a statistical analysis plan, or methods for missing outcomes.
The registry gives serious and other adverse-event counts and selected serious-event terms, but the available summary does not provide enough context to establish causes or treatment attribution for deaths and events. Term-specific percentage denominators are not reported in the registry record. These limitations constrain both safety interpretation and any attempt to compare the arms.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062) — NCT03099161.
- Registry record last updated 2019-06-05; status last verified 2019-02.
- Results first posted 2019-06-05.
- 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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19. Record Summary
The registry record describes NCT03099161, a non-randomized, unmasked, parallel-arm study listed as PHASE1 and terminated. It evaluated preladenant 25 mg BID, preladenant 50 mg BID, and preladenant 25 mg BID with pembrolizumab 200 mg in participants with advanced solid tumors. The primary endpoint was the number of participants with dose-limiting toxicities during Cycle 1, up to 21 days.
The study description states that early dose evaluation was intended to establish a recommended Phase 2 dose and that a later part was planned to assess the combination. The registry lists an enrollment of 10 and an objective response rate outcome, but does not report numerical primary-endpoint or response results. Adverse-event and death counts are descriptive and do not provide a randomized comparison. The reason for termination, missing-data procedures, and analysis plan are not reported in the registry record.